Hepatitis | EATG http://www.eatg.org European AIDS Treatment Group Fri, 19 Jan 2018 00:01:43 +0000 en-US hourly 1 https://wordpress.org/?v=4.8 Tenofovir alafenamide effectively treats HBV, no virologic resistance http://www.eatg.org/news/tenofovir-alafenamide-effectively-treats-hbv-no-virologic-resistance/ Thu, 18 Jan 2018 22:20:01 +0000 http://www.eatg.org/?post_type=news&p=7224 Treatment with tenofovir alafenamide was as effective in suppressing hepatitis B replication as tenofovir disoproxil fumarate with no virologic resistance, according to recently published data on two 96-week trials.

“Tenofovir alafenamide (TAF) is an orally bioavailable prodrug of tenofovir (TFV), a nucleotide analog that inhibits reverse transcription of HIV and HBV,” Kosh Agarwal, MD, from Kings College Hospital, United Kingdom, and colleagues wrote. “TAF was designed to have greater plasma stability than tenofovir disoproxil fumarate (TDF) allowing delivery of the active metabolite, tenofovir diphosphate, to hepatocytes more efficiently than TDF, which must be dosed at relatively high levels to achieve a therapeutic concentration in hepatic cells.”

Study GS-US-320-0110 included 792 patients who were positive for hepatitis B e-antigen and completed 96 weeks of treatment with either TAF 25 mg (n = 530) or TDF 300 mg (n = 262). Study GS-US-320-0108 included 395 patients who were negative for HBeAg and completed 96 weeks of treatment with either TAF (n = 266) or TDF (n = 129). The randomized, double-blind studies were identical in design.

HBeAg-positive study

At the end of 96 weeks, the proportion of patients who received TAF and had HBV DNA less than 29 IU/mL was 73% compared with 75% in those treated with TDF. The adjusted difference of –2.2% (95% CI, –8.3% to 3.9%) was not significant.

The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with alanine aminotransferase above the upper limit of normal at baseline who achieved normal ALT at week 96 was 75% in patients who received TAF and 68% in those who received TDF, which researchers reported was significant (8%; 95% CI, 1.2-14.7).

The rate of HBeAg loss between the two groups was 22% in patients who received TAF compared with 18% among those who received TDF. Additionally, the rate of HBeAg seroconversion was 18% in the TAF group compared with 12% in the TDF group. The data indicated neither sets of rates were significantly different.

HBeAg-negative study

At study end, the proportion of patients negative for HBeAg who received TAF and had HBV DNA less than 29 IU/mL was 90% compared with 91% in those treated with TDF. The adjusted difference of –0.6% (95% CI, –7% to 5.8%) was not significant.

The researchers observed treatment failure in 41 patients at week 96, eight of whom had verified HBV DNA of 29 IU/mL or higher between the TAF group (n = 5) and TDF group (n = 3).

The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with ALT above the upper limit of normal at baseline who achieved normal ALT at week 96 was 81% in patients who received TAF and 71% in those who received TDF, the difference of which was significant (9.8%; 95% CI, 0.2-19.3).

One HBeAg-negative patient treated with TAF experienced loss of HBV surface antigen and achieved seroconversion to anti-HBs. The researchers observed small but similar mean declines in HBsAg levels in both the TAF group (–0.14) and TDF group (–0.1).

“Consistent with week 48 results, treatment effects between TAF and TDF did not differ statistically in prespecified subgroups including age, race, region, HBV genotype, baseline HBV DNA level and prior oral antiviral treatment status,” the researchers wrote. “Through 96 weeks of double-blind treatment, no resistance development was seen in either treatment group. Further, the superior safety profile of TAF relative to TDF with regard to bone and renal parameters seen at week 48 is confirmed through 96 weeks of double-blind treatment.”

Agarwal K, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.11.039.

By Talitha Bennett

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Insulin resistance in HCV may be reversed with DAAs http://www.eatg.org/news/insulin-resistance-in-hcv-may-be-reversed-with-daas/ Thu, 18 Jan 2018 20:30:31 +0000 http://www.eatg.org/?post_type=news&p=7228 Hepatitis C (HCV) is associated with insulin resistance, and elimination of the virus may help re-establish glycemic control in affected patients, according to a prospective case-control study published in the Journal of Gastroenterology and Hepatology.

Investigators enrolled consecutive patients with HCV and advanced liver fibrosis who were being considered for direct-acting antiviral (DAA) medication (N=133). Researchers evaluated patients treated with DAAs (n=68) and untreated patients (n=65). At baseline, all patients were free of insulin resistance and type 2 diabetes.

At baseline, insulin resistance was 52.3% and 53.8% in treated and untreated patients, respectively. Various DAA treatments were used, including simeprevir + sofosbuvir (43%), ombitasvir/paritaprevir/ritonavir + dasabuvir (45%), and ledipasvir/sofosbuvi (12%). All patients had cleared their HCV at 3-month follow-up, with 95.6% of patients achieving a sustained virologic response.

Approximately 76.5% of patients who achieved a sustained virologic response experienced improvements in insulin resistance. There was a significant 2.42±1.85 point reduction in insulin resistance as assessed by the homeostatic model assessment insulin resistance (HOMA-IR) test (P <.001). Eradication of HCV was also associated with improved insulin sensitivity and decreases in serum blood glucose and insulin. Patients presenting with a high degree of fibrosis at baseline, however, maintained some level of insulin resistance following treatment (P <.04).

The relatively small number of patients included in this analysis prohibits establishing conclusive evidence on the true benefits associated of HCV treatment on reducing insulin resistance.

In addition to the main findings, the investigators also found that the body mass index (BMI) of patients remained unchanged following treatment, suggesting “that the changes in insulin resistance were independent of BMI [and] further supporting the role of HCV-genotype 1 in the development of insulin resistance.”

By Brandon May

Reference

Adinolfi LE, Nevola R, Guerrera B, et al. HCV clearance by direct-acting antiviral treatments reverses insulin resistance in chronic hepatitis C patients [published online December 11, 2017]. J Gastroenterol Hepatol. doi:10.1111/jgh.14067

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Elbasvir/grazoprevir plus ribavirin improves SVR in certain HCV genotypes http://www.eatg.org/news/elbasvirgrazoprevir-plus-ribavirin-improves-svr-in-certain-hcv-genotypes/ Thu, 18 Jan 2018 20:29:49 +0000 http://www.eatg.org/?post_type=news&p=7230 Elbasvir/grazoprevir (EBR/GZR) with or without ribavirin (RBV) appears to be tolerable and effective for achieving a sustained virologic response (SVR) at 12 weeks in certain genotype hepatitis C (HCV) infections, according to study findings published in the Journal of Viral Hepatitis.

In this randomized, open-label trial consisting of treatment-naive, noncirrhotic patients with HCV genotype 2, 4, 5, or 6 infection, investigators assessed the effect of EBR/GZR with or without RBV on SVR. Virologic response at 12 weeks after treatment made up the primary endpoint for this study. In addition, investigators evaluated the treatment’s associated adverse outcomes, including fatigue, headache, asthenia, nausea, and cough.

Those with the HCV genotype 2 infection were randomly assigned to receive GZR 100 mg in addition to RBV ± elbasvir 50 mg for 12 weeks. Participants with HCV genotype 4, 5, or 6 infection received EBR/GZR ± ribavirin for the same period. A SVR response at 12 months was achieved by 80% of participants with genotype 2 infection who were assigned to EBR/GZR plus RBV vs 73% of genotype 2 patients assigned to GZR and RBV.

Rates of SVR were fairly high among patients with HCV genotype 4 infection randomly assigned to EBR/GZR with and without RBV (100% and 90%, respectively). Adding RBV to the EBR/GZR combination therapy improved the 12-week SVR among patients with genotype 5 infection (EBR/GZR [25%] vs EBR/GZR plus RBV [100%]). Approximately 75% of patients with genotype 6 HCV infection in both the EBR/GZR and EBR/GZR plus RBV groups achieved a SVR at follow-up. In addition, patients receiving RBV experienced more frequent adverse events than patients receiving EBR/GZR.

The small number of patients with HCV genotypes 5 and 6 in this analysis limits the ability to draw firm conclusions on treatment “of people infected with these genotypes and the impact [of] resistance associated substitutions.”

By Brandon May

Reference

Brown A, Hézode C, Zuckerman E, et al; for the C-SCAPE Study Investigators. Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with HCV genotype 2, 4, 5, or 6 infection: the C-SCAPE study [published online November 20, 2017]. J Viral Hepat. doi: 10.1111/jvh.12801

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Smoking reduces survival after liver cancer diagnosis for people with viral hepatitis http://www.eatg.org/news/smoking-reduces-survival-after-liver-cancer-diagnosis-for-people-with-viral-hepatitis/ Thu, 18 Jan 2018 20:11:38 +0000 http://www.eatg.org/?post_type=news&p=7222

People with viral hepatitis who smoked were three times more likely to die after being diagnosed with liver cancer (hepatocellular carcinoma, HCC), according to a study of Swiss patients published in Liver International.

Whereas non-smokers lived for a median of 3.2 years after diagnosis, smokers died after a median of 18 months. Smoking had a similar impact on survival in those who did not receive curative treatment in the form of liver resection (surgery), liver transplantation or ablation (use of heat to destroy tumours in the liver).

Smoking has been found to increase the risk of developing liver cancer in some, but not all studies, and to increase the risk of liver cancer in some studies of people with viral hepatitis.

To look at the effect of continuing to smoke after a diagnosis of primary liver cancer (HCC) Swiss researchers analysed survival in 238 people with at least 12 months of follow-up after diagnosis of HCC. Sixty-four reported smoking at the time of inclusion in the cohort study. Smokers were followed for a median of 489 days and non-smokers for 1170 (p = 0.002), the difference reflecting the poorer survival in smokers.

HCC developed at a younger age in smokers (59 vs 66 years, p < 0.001).

There was no significant difference between smokers and non-smokers in the stage of liver cancer whether measured by Child-Pugh grade or BCLC (Barcelona Clinic Liver Cancer) system, nor in any markers of liver damage with the exception of platelet counts and INR (international normalised ratio) scores. Smokers showed some evidence of greater liver injury. They had lower platelet counts and slightly higher INR scores. (Smokers usually have higher platelet counts than non-smokers.)

There was no difference between smokers and non-smokers in the type of treatment they received.

HCC attributable to viral hepatitis (B or C) or alcohol was more common in smokers.

A multivariate analysis which controlled for other risk factors showed that smoking increased the risk of death in people with viral hepatitis diagnosed with HCC (HR 2.41, 95% CI 1.28-4.41, p = 0.007) but not in people with liver cancer attributable to other causes. A more advanced stage of HCC at diagnosis also increased the risk of death (HR 2.73, 95% CI 1.93-3.85, p < 0.001).

Smoking is known to increase liver fibrosis in people with hepatitis C and might also directly influence HCC progression after diagnosis. Poorer fitness or less compliance with medical treatment or advice might also affect survival, the investigators suggest. They say that it is not possible to tell from their cohort whether the effect of smoking was a consequence of smoking intensity – how many cigarettes a day – or duration (persistence in smoking after diagnosis).

“Based on these findings, smoking cessation should be considered for incorporation into the disease management for patients with HBV or HCV [with HCC],” the authors conclude. They point out that around 80% of HCC cases worldwide are probably attributable to viral hepatitis.

By Keith Alcorn

Reference

Kolly P et al. Effect of smoking on survival of patients with hepatocellular carcinoma. Liver International 37: 1682-1687, 2017.

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Injection drug users benefit from hepatitis C treatment http://www.eatg.org/news/injection-drug-users-benefit-from-hepatitis-c-treatment/ Thu, 18 Jan 2018 19:51:23 +0000 http://www.eatg.org/?post_type=news&p=7227 Since the emergence of costly direct-acting antiviral drugs, much controversy has surrounded the issue of which patients with hepatitis C virus (HCV) should receive treatment. Due to the high costs of these drugs, some payers only granted access to patients with late-stage cirrhosis.

The opioid epidemic and related boom in injection drug use has resulted in even more questions: should people who inject drugs (PWID) receive HCV treatment and if these patients do receive payer approval, will they respond to therapy?

A new study published by the Lancet Gastroenterology & Hepatology suggests that a majority of PWID can achieve a sustained viral response at 12 weeks.

Included in the analysis were 103 patients with HCV genotypes 1 to 4 who reported using injection drugs in the previous 6 months. Patients were treated with daily sofosbuvir-velpatasvir for 12 weeks.

At baseline, approximately three-quarters of patients used injection drugs within the previous month and 60% of patients received opioid substitution treatment.

The authors found that 99 out of 100 patients who finished treatment achieved a response.

Approximately 94% of patients achieved a sustained virologic response at 12 weeks, which was the primary efficacy endpoint of the trial, according to the study. The authors found that there were no virological failures.

Injection drug use prior to and during HCV treatment was not observed to impact virologic response, according to the study.

Less than half of patients experienced a treatment-related adverse event and only 7% experienced a serious adverse event. There was also a single case of HCV re-infection observed, according to the authors.

Current guidelines suggest that PWID should receive treatment for HCV, but several factors—including stigma—may prevent physicians from prescribing the drugs.

“Stigma … has resulted in insurance restrictions and reluctance from providers to offer appropriate medical therapy,” the authors wrote.

The authors note that physicians should offer HCV therapy to PWID and that recent injection drug use should not justify withholding drug reimbursement, according to the study.

These findings suggest that PWID with HCV “can and should be treated with direct-acting antivirals,” the authors concluded.

By Laurie Toich

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First chronic hepatitis B patient dosed in China in a Phase 1 trial of T101 (Transgene’s TG1050 technology) http://www.eatg.org/news/first-chronic-hepatitis-b-patient-dosed-in-china-in-a-phase-1-trial-of-t101-transgenes-tg1050-technology/ Wed, 17 Jan 2018 21:48:09 +0000 http://www.eatg.org/?post_type=news&p=7215 STRASBOURG, France, January 17, 2018: Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies, announces that the first patient has been dosed in a Phase 1 clinical trial in China, evaluating T101, a therapeutic vaccine based on Transgene’s immunotherapy technology for the treatment of chronic hepatitis B virus (HBV) infection. This product is a viral vector expressing the same suite of patented HBV antigens as in TG1050, currently in clinical development in Europe and North America.

T101 is being developed in China through Transgene’s joint-venture with Tasly Pharmaceutical Group Co, Ltd. This Chinese corporation was created in 2010 to develop biotechnology products, including Transgene products, in China. This company is jointly owned (50%/50%) with Tasly Pharmaceutical Group Co, Ltd, which is based in Tianjin, China.

The Phase 1 trial is a randomized, single-center, double-blind, placebo-controlled study evaluating T101 in patients who are currently being treated for chronic HBV infection with standard-of-care antiviral therapy. The primary objective of this study is to validate the tolerability of T101 administered in single and multiple ascending doses. The trial will also evaluate the immunogenicity of the therapeutic vaccine in a patient population whose characteristics differ from European and North American patients (e.g. different modes of contamination, different population haplotypes), and who can be infected with different genotypes of the virus. This trial will include up to 36 patients. The first data readout from the study is expected at the beginning of 2019.

Currently available antiviral treatments can control the chronic hepatitis B but not cure the disease. Even under chronic treatment, patients still have a high probability to develop cirrhosis and liver cancer. In China, 500,000 patients could benefit from a better therapeutic option.

T101 is a targeted immunotherapy candidate for the treatment of chronic hepatitis B, based on a viral vector expressing three HBV antigens. It has been designed by Transgene’s infectious diseases research team, based on the technology of Transgene’s therapeutic vaccine TG1050.

TG1050 is currently being evaluated by Transgene in a Phase 1/1b trial with TG1050 in chronic HBV patients treated with standard-of-care antiviral therapies in Europe and Canada. The first results from this clinical trial have confirmed the good tolerability profile of TG1050. This study has also demonstrated the dose-related immunogenicity of this novel therapeutic vaccine following a single administration to patients with chronic hepatitis B receiving standard antiviral therapy. Additional data on patients receiving multiple doses of TG1050 are expected to be presented at a major international conference dedicated to liver diseases in H1 2018.

About Transgene

Transgene (Euronext: TNG), part of Institut Mérieux, is a publicly traded French biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer and infectious diseases. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing infected or cancerous cells. The Company’s lead clinical-stage programs are: TG4010, a therapeutic vaccine against non-small cell lung cancer, Pexa-Vec, an oncolytic virus against liver cancer, and TG4001, a therapeutic vaccine against HPV-positive head and neck cancers. The Company has several other programs in clinical development, including TG1050 (chronic hepatitis B) and TG6002 (solid tumors).
Transgene is based in Strasbourg, France, and has additional operations in Lyon, as well as a joint venture in China. Additional information about Transgene is available at www.transgene.fr.

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Hepatitis C treatment highly effective in harder-to-treat HIV coinfected patients, Spanish real-life study shows http://www.eatg.org/news/hepatitis-c-treatment-highly-effective-in-harder-to-treat-hiv-coinfected-patients-spanish-real-life-study-shows/ Tue, 16 Jan 2018 22:40:02 +0000 http://www.eatg.org/?post_type=news&p=7206

Hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) is highly effective and safe in harder-to-treat HIV co-infected patients, Spanish researchers report in AIDS. A sustained virological response (SVR), or cure, was observed in 93% of patients and only 0.4% stopped treatment because of adverse events. The large proportion of patients had advanced fibrosis or had taken a previous course of HCV therapy. Liver cirrhosis/liver stiffness were the only factors associated with treatment failure and use of ribavirin increased the risk of side-effects.

Nevertheless, 87.5% of people with cirrhosis achieved a sustained virologic response and no one with cirrhosis who completed a 24-week course of treatment and underwent follow-up testing failed to be cured of hepatitis C. The study findings are highly encouraging for coinfected people with advanced liver disease – in the past considered harder to treat – the study investigators conclude.

“The present work considered a heterogeneous, unselected cohort of coinfected patients who were treated for their HCV infection under normal clinical practice conditions, and contrasts well with highly-selective randomized clinical trials which do not always equate well to real-life settings,” write the investigators.

“The real-life results of studies performed in developed countries implementing all-oral DAA based regimens in cohorts principally including difficult-to-treat patients (HIV coinfected, cirrhotic, and/or with previous therapy failures), confirm these results.”

Approximately a third of HIV-positive patients in Spain are co-infected with HCV. Liver disease caused by HCV is a leading cause of serious illness and death in co-infected patients. In recent years, HCV therapy using all-oral DAA regimens has been developed. In clinical trials, these combinations have achieved SVR rates in excess of 90%. However, there is relatively little data about the efficacy and safety of DAA combinations in HIV/HCV-co-infected patients with characteristics usually associated with poorer treatment outcomes, especially more advanced liver disease or therapeutic failure using older regimens.

Investigators in eastern Spain therefore analysed outcomes in 515 co-infected patients who started an all-oral DAA regimen in 2015. Retrospective data were obtained on the proportion of patients attaining an SVR twelve weeks after completing a twelve or 24-week course of therapy, and also the proportion of patients experiencing adverse events. The investigators also conducted a series of analyses to see if specific patient or treatment factors were associated with the success of therapy or a greater risk of side-effects.

A total of 13 treatment centres in the region close to Valencia participated in the study. The patients had a median age of 50 years and 78% were male. Most (84%) had injecting drug use as their most likely mode of HCV infection. The most common HCV genotype was 1a (47%), with 20% carrying genotype 4 and 14% genotype 1b and 13% genotype 3. Just over half (54%) had cirrhosis, which was diagnosed using elastography (FibroScan, an assessment of liver stiffness) in 95% of patients. Just under half (46%) had taken a previous unsuccessful course of HCV therapy based on pegylated interferon or first-generation DAAs.

As regards HIV infection, 95% of individuals were taking antiretroviral therapy (ART) and 90% had a viral load below 50 copies/ml. Median CD4 cell count was 585 cells/mm3. To avoid potential drug interactions, a third of patients modified their ART before staring DAA therapy. The new combinations were mostly based on an integrase inhibitor.

The most widely used DAA regimen was ledipasvir/sofosbuvir (LDV/SOF; 57%). Just over third of patients (37%) were treated with a ribavirin-containing regimen and 7% took a 24-week course of therapy.

Overall, 93% of patients had sustained virological response twelve weeks after the completion of therapy.  There was little evidence that outcomes were influenced by baseline characteristics such as age and sex, HCV viral load or previous use of HCV therapy.

The only factors associated with reduced chances of attaining SVR were cirrhosis (p = 0.001) and liver stiffness above 21kPa (p = 0.001).

Only two patients (0.4%) stopped treatment because of adverse events, one because of decompensated cirrhosis, the other due to newly diagnosed high-grade lymphoma. Overall, 37% of patients reported any adverse events. These were mild in the majority of cases. Adverse events were reported by 54% of the ribavirin-treated patients, with 27% requiring dose reduction.

The investigators’ analyses failed to identify any significant association between specific DAA regimens and the risk of adverse events. However, ribavirin was associated with a nearly three-fold increased risk of side-effects.

“In real-life conditions, difficult-to-treated HIV/HCV-coinfected patients treated with all-oral DAA combinations reach high rates of SVR12, similar to those achieved by monoinfected patients in such conditions,” conclude the authors.

“Future drugs should be focused on reducing the risk of drug-drug interactions, along with an improvement in efficacy in patients with increased liver stiffness.”

By Michael Carter

Reference

Mínguez C et al. Interferon-free therapy for treating HCV in difficult-to-treat HIV-coinfected patients as implemented in routine medical practice. AIDS, online edition. DOI: 10.1097/QAD/0000000000001699 (2018).

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Hepatitis A vaccines effective in high-risk populations during outbreak http://www.eatg.org/news/hepatitis-a-vaccines-effective-in-high-risk-populations-during-outbreak/ Mon, 15 Jan 2018 21:30:13 +0000 http://www.eatg.org/?post_type=news&p=7198 Two-dose hepatitis A vaccination was an effective preventive measure among HIV-positive individuals, including a high study population of men who have sex with men, during an ongoing outbreak of acute HCV, according to recently published data.

“We found that HAV vaccination was highly effective in preventing acute HAV infection during the outbreak, despite the delayed serologic response among HIV-positive individuals,” Kuan-Yin Lin, MD, from the National Taiwan University Hospital, and colleagues wrote. “Our results support HAV serologic screening and vaccination for those at-risk HIV-positive populations in the era of [combination antiretroviral therapy] scale-up.”

Since June 2015, Taiwan has experienced an ongoing outbreak of acute HAV with 1,440 indigenous cases reported as of Sept. 30, 2017. According to the researchers, up to 70% of the reported cases were MSM and up to 60% were HIV-positive patients.

To investigate the serologic response and efficacy of two-dose HAV vaccination among patients with HIV during a large outbreak of acute HAV, the researchers prospectively followed 1,533 adult patients who were seronegative for HAV and positive for HIV from June 1, 2015, to Sept. 30, 2016. Most patients were MSM (94.1%).

Among those enrolled, 1,001 received at least one dose of HAV vaccine and 532 did not. At the end of follow-up, 965 of the vaccinated patients received a second dose and completed 48 weeks of follow-up.

During follow-up, 60 unvaccinated patients and five vaccinated patients acquired HAV. Fifty of the unvaccinated patients had acute HAV and 10 were asymptomatic seroconversion. All patients with acute HAV were MSM and more than 50% had concurrent syphilis.

The incidence rate of acute HAV infection was 3.7 per 1,000 person-years in the vaccinated group and 99.3 per 1,000 person-years in the unvaccinated group.

After multivariate analysis, patients with HIV who received HAV vaccine had significantly reduced risk for HAV infection (HR = 0.04; 95% CI, 0.02-0.1) and acute HAV (HR = 0.05; 95% CI, 0.02-0.14). The prevention rate was 96% for HAV (95% CI, 90-98) and 95% for acute HAV (95% CI, 86-98).

In contrast, acquisition of syphilis during the follow-up correlated with occurrence of acute HAV infection (HR = 3.87; 95% CI, 2.34-6.42) and acute HAV (HR = 4.04; 95% CI, 2.33-7.02).

The seroconversion rate was 7.7% at 4 weeks after the first dose of vaccination, which increased to 21.1% at weeks 5 through 8, 54.2% at weeks 9 through 12, 58.5% at weeks 13 through 16, 64.2% at weeks 17 through 20, and 57.3% between week 21 and the administration of the second dose of HAV vaccine.

Results of an intent-to-treat analysis showed a seroconversion rate of 63.8% at weeks 28 through 36 and 55.4% at week 48, after administration of a second dose. After the researchers applied a last observation carried forward approach, the seroconversion rate was 71.6% at weeks 28 through 36 and 88.4% at week 48. Per-protocol analysis showed a seroconversion rate of 93.7% at weeks 28 through 36 and 94.5% at week 48.

Further adjusted analysis showed an association between seroconversion at weeks 28 through 36 with a younger age (per one-year decrease, OR = 1.08; 95% CI, 1.02-1.12) and undetectable plasma HIV RNA load (PVL) at vaccination (OR = 3.19; 95% CI, 1.32-7.68).

“Despite the delayed and suboptimal serologic response, HAV vaccination was still clinically effective in preventing acute HAV infections,” the researchers concluded. “Improved surrogates of immune status, such as higher CD4 counts, and suppressed PVL, enhanced the immunogenicity to the two-dose vaccine series.”

Lin KY, et al. Hepatol. 2017;doi:10.1002/hep.29780.

By Talitha Bennett

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Serological method could replace molecular for HCV testing http://www.eatg.org/news/serological-method-could-replace-molecular-for-hcv-testing/ Mon, 15 Jan 2018 21:27:33 +0000 http://www.eatg.org/?post_type=news&p=7196 Serologic detection of hepatitis C virus antigen (HCV-Ag) could replace the previous detection standard of molecular HCV-RNA in the era of direct-acting antivirals (DAAs), as DAA effectiveness in treating HCV is not predicted by baseline HCV-RNA levels, and successful treatment is no longer marked by absence of residual HCV-RNA.

“To simplify treatment monitoring, hepatitis C core antigen is emerging as a new tool for diagnosis and treatment monitoring in chronic HCV infection,” wrote principle investigator Pietro Andreone, MD, Department of Medical and Surgical Sciences, University of Bologna, Bologna Italy, and colleagues.

Andreone, and lead author Elisabetta Loggi, PhD, currently at the UOC Patologica Clinica, Fermo, Italy, elaborated on the advantages of applying the serologic testing of HCV-Ag in a statement to MD Magazine.

“Certainly, the main advantage is the general workflow simplification: the automated HCV-Ag testing doesn’t require sophisticated laboratory facilities, specialized technicians, has a much faster turnaround time and lower costs,” Andreone and Loggi said.

Although the HCV-Ag testing has a lower level of sensitivity than HCV-RNA detection, Andreone and Loggi posed the question of whether there is still a need for virological testing with high sensitivity in the DAA era.

The change to DAA treatment from pegylated interferon-based protocols has obviated the need for baseline levels of RNA in order to categorize the patient or to tailor therapy. Also, successful treatment is no longer marked by an absence of HCV-RNA, but by sustained virologic response (SVR).  In addition, there is no longer a “futility/stop treatment” measure from HCV-RNA that is used with DAA regimens.

“A residual viremia during the treatment is currently disregarded, as it does not imply a modification of treatment schedule,” Andreone and Loggi said.

To ascertain the clinical utility of the less costly and more accessible HCV-Ag detection method for monitoring treatment response compared to HCV-RNA, the investigators obtained both values periodically through DAA treatment of 96 consecutive, all-genotype patients with chronic HCV infection presenting to University of Bologna associated outpatient clinics between June 2013 and December 2015.

The investigators found expected patterns. There was a very rapid decrease in HCV-RNA, with negative detection increasing from mean of 16% after 2 weeks, to 55% after 4 weeks, and 99% after 8 weeks of treatment.  The kinetics of HCV-Ag was expectedly different, with 63% negative after 2 weeks and then a slower progression during treatment to 74% after 4 weeks and 83% after 8 weeks.

At the end of treatment, however, all patients except 1 with breakthrough viremia were negative for both HCV-RNA and HCV-Ag.

“Our recent work, in agreement with other similar experiences, showed a general clinical equivalence between HCV-Ag and HCV-RNA monitoring,” Andreone and Loggi said. “Both present a similar kinetic disappearance from serum during DAA treatment, despite the lower sensitivity of HCV-Ag, which does not seem to limit the performance of the test.”

The researchers opined that HCV-Ag is a strong candidate for simplified, cost-saving virological testing for HCV, and should be implemented “both as index of viral replication and to assess the response to pharmacological treatment.”

The study, “Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods,” was published online in PLOS one in November.

By Kenneth Bender

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Epidemiological update: hepatitis A outbreak in the EU/EEA mostly affecting MSM http://www.eatg.org/news/epidemiological-update-hepatitis-a-outbreak-in-the-eueea-mostly-affecting-msm-2/ Mon, 25 Dec 2017 17:47:17 +0000 http://www.eatg.org/?post_type=news&p=7129 Since the last epidemiological update on this multi-country hepatitis A outbreak published on 29 September 2017, 22 EU/EEA countries (Austria, Belgium, Croatia, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Luxembourg, Malta, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden and the United Kingdom-England & Wales) have reported 950 new outbreak-confirmed cases. Outbreak-confirmed cases are EU/EEA residents with laboratory-confirmed hepatitis A virus (HAV) genotype IA and a sequence with ≥99.3% homology to one of the three HAV genotype IA outbreak strains (VRD_521_2016; RIVM-HAV16-090; and V16-25801) based on overlapping fragments at the VP1-2a region.

Read the full ECDC update here.

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Treatment regimens and recommendations for HIV/HCV coinfection http://www.eatg.org/news/treatment-regimens-and-recommendations-for-hivhcv-coinfection/ Thu, 21 Dec 2017 04:45:19 +0000 http://www.eatg.org/?post_type=news&p=7118 Challenges in Treatment of HIV and HCV Coinfection

Coinfection with HIV and hepatitis C virus (HCV) is common. In the United States, up to one-third of those with HIV are coinfected with HCV and one-third of those with HCV are coinfected with HIV.1,2 The high prevalence of HIV and HCV coinfection is likely the result of shared modes of transmission for both types of infection, such as intravenous drug use, sexual contact, or mother-to-child transmission.3

“We need to be aggressively treating everyone with HCV, including and especially patients who are coinfected with HIV, because we know that patients who are coinfected are at higher risk for more rapid progression of liver disease,” Lisa Chirch, MD, FIDSA, Associate Professor of Medicine in the Infectious Diseases department at UConn Health in Connecticut, told Infectious Disease Advisor. Liver cirrhosis will develop in approximately one-third of patients with HCV and HIV coinfection within 20 years. Additionally, patients with coinfection are 3 times more likely to have progression to decompensated liver disease or cirrhosis than are patients with HCV infection alone.4

Previously, the only therapies available for HCV infection were pegylated interferon and ribavirin, which were often ineffective at disease control and poorly tolerated. The development of next-generation direct-acting antivirals (DAAs) for HCV has led to significantly improved sustained virologic response rates and better tolerability in people with both HIV/HCV coinfection and those with HCV alone.4 Consequently, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidelines for HCV treatment recommend that people with HCV and HIV coinfection be treated similarly to those with HCV monoinfection.5

Whereas the new oral DAAs make viral suppression of HCV an achievable goal in patients with HCV/HIV coinfection, the simultaneous use of HIV antiretroviral therapy (ART) presents new challenges regarding drug-drug interactions (DDIs). Infectious Disease Advisor spoke with Dr Chirch and with Oluwaseun Falade-Nwulia, MBBS, MPH, Assistant Professor of Medicine in the Infectious Diseases department at Johns Hopkins Medicine in Maryland, about the management of DDIs in patients receiving treatment for HIV and HCV coinfection.

Resources to Identify DDIs in HIV and HCV Regimens

“Providers who treat patients with HIV and HCV coinfection need to be aware of DDIs between HIV and HCV medications to prevent bad outcomes that are potentially avoidable,” Dr Falade-Nwulia said.

“We have so many options for HCV therapy now that we are in a position to treat any [patient coinfected with] HIV/HCV,” she added. However, with numerous potential HIV and HCV drug combinations, many DDIs are possible. Staying current on what DDIs may occur with all HIV and HCV medication combinations would be an impossible task.

Fortunately, several tools are available to aid clinicians in selecting HIV and HCV regimens that minimize DDIs. Dr Falade-Nwulia recommends consulting the user-friendly tables published in the AASLD/IDSA guidelines for the treatment of HCV infection. The tables can be found under the section, “Unique Populations: Patients with HIV/HCV Coinfection.”5 The tables are color coded to indicate which drug combinations are safe and which ones should be avoided because of DDIs.

Dr Chirch suggests additional resources, such as the HIV treatment guidelines issued by the US Department of Health and Human Services, which are updated at least once yearly and contain a section on drug-drug interactions.6 The AIDS Education & Training Center Program: Northeast/Caribbean has developed charts on DDIs for HIV medications as clinical support tools.7 In particular, Dr Chirch recommends the University of Liverpool’s HEP iChart website and mobile phone app, which may be used to identify DDIs between HIV ART agents and any other medication.8 “It’s really easy to use. I end up using this app very frequently,” she said. “If you plug in the medications that your patient is on and then plug in the medication that you want to use, it is difficult to miss any major problems.”

Important DDIs in HIV and HCV Treatment

Although resources are available to identify potential DDIs between HIV and HCV antiviral drugs, some general principles may help guide treatment selection. “The most recent iteration of the guidelines for the treatment of HIV recommend integrase inhibitor-based ART regimens as preferred regimens,” Dr Chirch said. DDIs are not as common with integrase inhibitors — which include dolutegravir, raltegravir, and elvitegravir — because they are metabolized by the uridine diphosphate glucuronosyltransferase pathway instead of by the CYP3A4 P450 system. However, Dr Chirch advised caution when using the integrase inhibitor elvitegravir because it requires boosting with cobicistat, which uses the CYP3A4 P450 enzyme, thus increasing the potential for DDIs.

According to Dr Chirch, some drug combinations should be avoided altogether. Protease inhibitors are widely used in the treatment of HCV and include grazoprevir, glecaprevir, and voxilaprevir. However, use of certain protease inhibitors for HCV with a boosted protease inhibitor for HIV that inhibits CYP3A4 P450 may elevate levels of the protease inhibitor for HCV, increasing the risk for liver toxicity in patients coinfected with HIV/HCV who already have some degree of liver disease. On the other hand, the ART agent efavirenz induces CYP3A4 P450, which may lead to lower levels of the co-administered drug, thereby potentially reducing its efficacy. “Efavirenz coadministration with most currently prescribed DAA regimens may be problematic, so that is one antiretroviral agent that you would consider switching off of if you were in that situation,” Dr Chirch said.

Tenofovir disoproxil fumarate (TDF), a nucleoside reverse transcriptase inhibitor commonly prescribed for HIV, is associated with renal toxicity. This risk may be further increased if TDF is used with some oral DAA therapies for HCV, according to Dr Falade-Nwulia. In particular, boosted protease inhibitor regimens may increase TDF exposure and raise the risk for renal toxicity. However, some combinations of TDF-based regimens plus oral DAAs for HCV present only a mild or moderate risk for renal toxicity, and therefore continuing treatment while closely monitoring kidney function may be an acceptable approach. A newer formulation of tenofovir, tenofovir alafenamide, is less nephrotoxic and has no DDIs with any of the oral DAA regimens for HCV.

Although no longer a preferred agent for HCV, ribavirin still sees use in combination with DAAs in patients who are treatment experienced or have liver cirrhosis. Using ribavirin-based regimens with some of the older nucleoside reverse transcriptase inhibitors — didanosine or zidovudine, for example — may lead to overlapping toxicities such as hepatic steatosis and lactic acidosis, and these combinations should be avoided, Dr Chirch said. Ribavirin can also cause dose-related hemolytic anemia, particularly when used with pegylated interferon. However, with newer agents available to treat HCV, anemia is now seen less frequently with ribavirin.

Managing DDIs in HIV/HCV Coinfection

The key principle to managing DDIs between HIV ART and HCV DAA therapy is to anticipate the problem before it occurs to prevent DDIs from happening, Dr Chirch said. In some cases, however, avoiding drug combinations that may lead to DDIs is not a feasible option. Some patients coinfected with HIV and HCV require a specific HCV regimen that is known to interact with their HIV regimen. If ribavirin must be used, for example, reducing the dose may help alleviate the risk for DDIs. The doses and dosing schedules of most other ART and DAA agents cannot be changed.

If the patient needs to be on a particular oral DAA regimen because of HCV genotype or severity of liver disease, their HIV ART treatment may need to be changed if the combination of regimens increases the risk for DDIs. “We are in a wonderful position now with so many options with ART that you can work with the patient to change their HIV regimen so that they are on a regimen that allows them to take an HCV oral DAA regimen,” Dr Falade-Nwulia said.

Before changing a patient’s HIV regimen, the clinician needs to ensure that the new regimen will maintain virologic suppression of HIV. Dr Chirch recommends obtaining a thorough history of prior ART regimens that have not worked for the patient and results of resistance testing to avoid using ART agents that may be ineffective and result in suboptimal outcomes.

Changing a patient’s HIV regimen also involves coordinated decision making with the patient. “You need to prepare the patient for the change,” Dr Falade-Nwulia said. “Sometimes [people with] HIV have been on their ART regimen for a really long time and they feel comfortable with this regimen.” Before starting HCV therapy, Dr Falade-Nwulia will switch the HIV regimen and monitor the patient for side effects and disease stability on the new regimen. She will then initiate HCV therapy once it becomes clear that the new HIV regimen is effective and the patient is comfortable with the treatment.

Modifying the HIV regimen to avoid DDIs with an HCV regimen is a complex and involved process. However, in a cohort study of 255 patients published in Hepatology, Dr Falade-Nwulia and colleagues found that only 30% of patients with HIV and HCV coinfection had to change their HIV regimens prior to starting DAAs for HCV.9 “Fortunately, the vast majority of patients with HIV/HCV coinfection do not require a switch in HIV therapy,” she said.

By Crystal Wong

References

  1. Scott JA, Chew KW. Treatment optimization for HIV/HCV co-infected patients. Ther Adv Infect Dis. 2017;4:18-36.
  2. Rice DP, Faragon JJ, Banks S, Chirch LM. HIV/HCV antiviral drug interactions in the era of direct-acting antivirals. J Clin Transl Hepatol. 2016;4:234-240.
  3. Qadir MI. Hepatitis in AIDS patients [published online: October 13, 2017]. Rev Med Virol. doi: 10.1002/rmv.1956
  4. Poizot-Martin I, Naqvi A, Obry-Roguet V, et al; Hepadat’AIDS Study Group. Potential for drug-drug interactions between antiretrovirals and HCV direct acting antivirals in a large cohort of HIV/HCV coinfected patients. PLoS One. 2015;10:e0141164.
  5. AASLD, IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Updated September 21,2017. Accessed November 28, 2017.
  6. US Department of Health and Human Services, AIDSinfo. Clinical Guidelines. Updated November 28, 2017. Accessed November 28, 2017.
  7. AETC Northeast/Caribbean. HCV drug interactions Guides—includes interactions with HIV and primary care medications. Updated 2017. Accessed November 28, 2017.
  8. University of Liverpool. HEP drug interaction checker. Reviewed November 28, 2017. Accessed November 28, 2017.
  9. Falade-Nwulia O, Sutcliffe C, Moon J, et al. High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center. Hepatology. 2017;66:1402-1412.
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New paper launched on hepatitis testing in community setting http://www.eatg.org/news/new-paper-launched-on-hepatitis-testing-in-community-setting/ Thu, 21 Dec 2017 03:35:15 +0000 http://www.eatg.org/?post_type=news&p=7100 Correlation Network announced the publication of a new paper on the importance of HCV testing in the Community! It includes background information, methods, good practices and much more.

Check out the paper here.

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MSF challenges Gilead’s patent application for hepatitis C combination treatment in China, to bring down prices http://www.eatg.org/news/msf-challenges-gileads-patent-application-for-hepatitis-c-combination-treatment-in-china-to-bring-down-prices/ Thu, 21 Dec 2017 03:32:21 +0000 http://www.eatg.org/?post_type=news&p=7108 Gilead recently launched one of these drugs for $100/pill in China

Geneva, 18 December 2017 – The international medical humanitarian organisation, Médecins Sans Frontières (MSF) has filed a legal patent challenge in China against US pharmaceutical corporation Gilead’s patent application for the combination of two crucial oral hepatitis C medicines, sofosbuvir and velpatasvir. This combination is the first direct-acting antiviral (DAA) treatment to be registered for use against all genotypes of the disease. Rejection of patents for this combination would pave the way towards the availability of affordable generic versions of this treatment that millions of people need in China and around the world.

The legal challenge, filed at the China State Intellectual Property Office (SIPO), offers technical grounds to show that the drug combination does not merit patenting under China’s Patents Law. If granted, the unjustified patent on the combination of these two medicines would give Gilead a monopoly over production and sale of the treatment in China. It would block Chinese generic companies from producing affordable versions, for use in China and globally.

“Despite the deadly toll the hepatitis C epidemic takes, pharmaceutical corporations like Gilead still have far too much control over who can access these lifesaving medicines, which is ultimately costing people their lives,” said Mickael Le Paih, Head of Mission for MSF in Cambodia. “In some high-burden countries where we work, hepatitis C treatment is not readily available due to high prices. Leveraging China’s ability to produce more affordable generics could significantly increase competition and bring prices down further, allowing many countries to get treatment to more people, faster.”

Globally, an estimated 71 million people have chronic hepatitis C infection and, without access to treatment, nearly 400,000 people die each year from its complications. With nearly nine million people infected, China has the highest prevalence of hepatitis C in the world. Yet access to these medicines that have proven to be a major breakthrough for the treatment of hepatitis C remains limited in China and many other middle-income countries due to exorbitant pricing.

In China, Gilead recently announced the market launch of sofosbuvir at a prohibitive price of US$8,937 per treatment course, or around $100 per pill. The price of the sofosbuvir and velpatasvir combination in China is still not known, as the treatment is not yet registered or available in the country; but using sofosbuvir at Gilead’s price, in combination with another DAA, daclatasvir, would cost about $12,000 for the 12-week treatment. Generic competition has driven the price of this same treatment combination to as low as $120 per 12-week treatment in countries where patent barriers do not exist.

“With this patent challenge, MSF hopes to prevent Gilead from getting unmerited patent rights on the combination of sofosbuvir and velpatasvir, which would allow them to charge unreasonably high prices,” said Yuanqiong Hu, Legal Advisor for MSF’s Access Campaign. “The world desperately needs more affordable sources of these essential hepatitis C medicines to save lives and contain this growing epidemic, and the best way to achieve this is to open the door widely to robust competition among generic producers.”

Gilead has applied for multiple patents in China for its hepatitis C medicines, and some of these are being opposed by other pharmaceutical companies and non-profit organisations based on similar grounds of being unmerited under China’s Patents Law. Since 2015, SIPO rejected two key patent applications for sofosbuvir in China. Gilead’s patent applications on sofosbuvir and its combinations have also been challenged in many other countries, including Brazil, India, Russia and the United States, as well as in the European Union. Some of the Gilead’s patent applications have been rejected in Argentina and Egypt.

MSF treats people with hepatitis C in 11 countries (Belarus, Ukraine, Pakistan, Uzbekistan, India, Myanmar, Cambodia, Uganda, Kenya, Mozambique and South Africa). Since 2015, MSF has provided DAA treatment to over 5,000 people with hepatitis C. Of those who have completed treatment to date, the overall cure rate – measured by ‘sustained viral response’ – is 94.9 per cent.

Information on currently available diagnostics and treatments for hepatitis C, including pricing and registration information from manufacturers of DAAs, can be found in MSF’s issue brief, Not Even Close.

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VBI Vaccines announces initiation of Phase 3 clinical program for Sci-B-Vac® hepatitis B vaccine http://www.eatg.org/news/vbi-vaccines-announces-initiation-of-phase-3-clinical-program-for-sci-b-vac-hepatitis-b-vaccine/ Thu, 21 Dec 2017 03:03:55 +0000 http://www.eatg.org/?post_type=news&p=7106 Patient dosing commenced on December 18, 2017
4,800 subjects across two Phase 3 studies: PROTECT and CONSTANT
15-month program – headline data expected Q2 2019

December 19, 2017: VBI Vaccines Inc. (Nasdaq: VBIV) (TSX: VBV) (“VBI”) announced today the initiation of the global Phase 3 clinical program for Sci-B-Vac®, its third-generation hepatitis B vaccine, with the commencement of patient dosing on December 18, 2017.

The Phase 3 program will be a global 15-month program consisting of two concurrent Phase 3 studies – a safety and immunogenicity study (PROTECT) and a lot-to-lot consistency study (CONSTANT), enrolling a total of approximately 4,800 subjects. The Phase 3 program will be conducted at approximately 40 sites across the U.S., Europe, and Canada.

Dr. Francisco Diaz-Mitoma, VBI’s Chief Medical Officer, commented, “The initiation of this Phase 3 program is a significant milestone for VBI. There is an extensive safety and efficacy data package that currently exists for Sci-B-Vac, with approximately 2,000 subjects in past clinical trials and over 500,000 subjects who have received the vaccine in the commercial setting. Pending data from this Phase 3 program, we expect to submit marketing authorization applications to U.S., European, and Canadian regulatory authorities in 2019. We believe there is a recognized need for an improved Hepatitis B vaccine and we are committed to advancing Sci-B-Vac through Phase 3 development as quickly as possible.”

Dr. Nathan Segall, a certified internal medicine, allergy, and immunology specialist at Clinical Research Atlanta and a Principal Investigator in the program, added, “Sci-B-Vac is the only commercially-available vaccine that contains the pre-S1 and pre-S2 surface antigens. The field is looking forward to seeing the results of this pivotal program, adding to the growing body of research which suggests that the inclusion of these two antigens may prove more immunogenic, especially in subjects that currently do not respond optimally to current standard of care.”

About PROTECT – Safety and Immunogenicity Study

PROTECT will be a double-blind, two-arm, randomized, controlled study. Approximately 1,600 adult subjects, 18 years of age and older, will be randomized in a 1:1 ratio to receive either a three-dose course of Sci-B-Vac 10μg or a three-dose course of the control vaccine, Engerix-B® 20μg. Enrollment will be stratified by age group.

The co-primary objectives of the study will be:

  • To demonstrate non-inferiority of the seroprotection rate induced by Sci-B-Vac vs. Engerix-B® four weeks after the third vaccination in adults age 18 and older.
  • To demonstrate superiority of the seroprotection rate induced by Sci-B-Vac vs. Engerix-B® four weeks after the third vaccination in adults older than 45 years of age.

The study will also include multiple secondary objectives to evaluate the speed to seroprotection, including assessment after two doses of Sci-B-Vac vs. three doses of Engerix-B®, and the overall safety and tolerability of Sci-B-Vac vs. Engerix-B®.

About CONSTANT – Lot-to-Lot Consistency Study

CONSTANT will be a double-blind, four-arm, randomized, controlled study. Approximately 3,200 adult subjects, age 18-45 years, will be randomized in a 1:1:1:1 ratio to receive one of four three-dose courses: Lot A of Sci-B-Vac 10μg, Lot B of Sci-B-Vac 10μg, Lot C of Sci-B-Vac 10μg, or the control vaccine Engerix-B® 20μg.

The primary objective of this study will be:

  • To demonstrate lot-to-lot consistency for immune response as measured by geometric mean concentration (GMC) of antibodies across three independent, consecutive lots of Sci-B-Vac four weeks after the third vaccination.

The secondary objective will be to evaluate safety and efficacy of Sci-B-Vac vs. Engerix-B®.

About Sci-B-Vac®

Sci-B-Vac® is a licensed third-generation hepatitis B vaccine that has demonstrated safety and efficacy in over 500,000 patients. Sci-B-Vac is currently approved for use in Israel and in 14 other countries. In contrast to second-generation hepatitis B vaccines, which contain only one surface antigen (the S antigen), Sci-B-Vac contains the S antigen and the pre-S1 and pre-S2 surface antigens. The composition of Sci-B-Vac may prove more immunogenic in subjects that currently do not respond optimally to second-generation vaccines.

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Should uninfected patients accept hepatitis C-infected livers to reduce waiting time? http://www.eatg.org/news/should-uninfected-patients-accept-hepatitis-c-infected-livers-to-reduce-waiting-time/ Wed, 20 Dec 2017 22:25:58 +0000 http://www.eatg.org/?post_type=news&p=7099 Study suggests that antiviral drugs may allow safe transplantation of HCV-positive livers into uninfected recipients.

A modeling study by Massachusetts General Hospital (MGH) investigators finds that the availability of directly-acting antiviral (DAA) drugs to treat hepatitis C virus (HCV) infection could allow the transplantation of livers from HCV-positive donors into HCV-negative recipients without posing undue risk. The team’s report will appear in the journal Hepatology and has been released online.

“The availability of donor livers continues to be the limiting factor in increasing the number of liver transplant surgeries,” says Jagpreet Chhatwal, PhD, of the MGH Institute for Technology Assessment, lead and corresponding author of the report. “Our study shows that transplanting HCV-positive livers into HCV-negative patients and treating with new antivirals can reduce waiting time to transplant and improve overall life expectancy.”

It is not uncommon for HCV-positive organs to be discarded and not utilized for transplant because of the risks associated with HCV infection after transplantation. The recent availability of DAA drugs to treat HCV-positive recipients has led to post-transplant cure rates greater than 90 percent, significantly improving overall transplant success. DAA drugs have also reduced the number of HCV-infected patients who progress to the point of requiring a transplant, increasing the proportion of patients needing a transplant for reasons other than HCV infection. At the same time, the persistent opioid epidemic has led to a greater number of potential donors infected with HCV, who are often young and otherwise healthy. All of these factors have led to increased interest in exploring the possibility of utilizing HCV-positive livers in HCV-negative patients on the transplant waiting list.

Since a randomized clinical trial of the use of HCV-infected donor livers in HCV-negative recipients would need to be large and conducted over several years, the MGH team decided to conduct a virtual trial by simulating the life courses of HCV-negative patients on the waiting list, and comparing probable outcomes under two scenarios – waiting for an HCV-negative liver or being open to accepting any appropriate liver, with the initiation of antiviral treatment if an HCV-positive liver was used. Based on the profiles of multiple patients on the liver transplant waiting list, the model included factors such as each patient’s probable waiting time, based on disease severity and geographic region; the supply of donor livers in each region, the risk of complications from an HCV-positive liver, and the efficacy of post-transplant antiviral treatment.

Their analysis revealed that the benefit of accepting an HCV-positive liver outweighs the risks in the majority of patients on the transplant waiting list. The magnitude of the benefits depended on the severity of a patient’s liver disease, which is measured by what is called a MELD score. Determined by a number of laboratory values, the MELD score ranges from 6 to 40, with a higher score indicating more severe illness. Patients can be referred for transplant evaluation with a score as low as 12, but the average MELD score for undergoing transplant is 28.

The MGH team found that HCV-negative patients with MELD scores of 20 or higher could benefit from receiving an HCV-positive liver, followed by antiviral treatment. The benefits were greatest for patients with scores of 28 and in regions hard hit by the opioid epidemic, such as the Northeast, that have greater numbers of HCV-positive donors.

“Prior to the availability of DAA drugs, the risks of transplanting HCV-positive livers into HCV-uninfected recipients were felt to be prohibitively high and not justifiable,” says Raymond Chung, MD, director of Hepatology, medical director of the MGH Liver Transplant Program and a co-author of the paper. “Every patient has extensive discussions with their care providers during the transplant listing process, part of which includes discussing the potential of accepting a ‘high-risk’ donor organ, such as one that tests positive for HCV. More clinical studies evaluating the use of HCV-positive donor livers and the efficacy and optimal treatment duration for antiviral drugs will be needed before this approach can be widely applied.”

Co-lead author Sumeyye Samur, PhD, of the MGH Institute for Technology Assessment says, “By simulating a virtual trial, we could assess the benefits and risks of transplanting HCV-positive organs into HCV-negative patients without putting patients at risk. Our study can thus inform efficient design of future trials and clinical practice in liver transplantation.”

Co-author Emily Bethea, MD, of MGH Gastroenterology and the Institute for Technology Assessment adds, “DAA treatment is expensive and is only covered by insurers for patients with documented HCV infection. If we hope to expand future coverage to HCV-negative patients on the transplant waiting list, we will need data on the cost-effectiveness of preemptive antiviral therapy to help payers recognize the importance and long-term success of this approach.”

Chhatwal stresses that, while the opioid epidemic has led to the increased availability of HCV-positive organs of all types, the trend should not be seen as beneficial. “The opioid epidemic is a major health crisis affecting communities across the country, and we want to reiterate our support for efforts to address the growing epidemic.”

Chhatwal is an assistant professor, Samur and Bethea are fellows, and Chung is an associate professor at Harvard Medical School. Additional co-authors of the Hepatology paper are Chin Hur, MD, MPH, MGH Institute for Technology Assessment; Turgay Ayer, PhD, Georgia Institute of Technology; Fasiha Kanwal, MD, MSHS, Baylor College of Medicine; Mark S. Roberts, MD, MPP, University of Pittsburgh School of Medicine; and Norah Terrault, MD, University of California San Francisco Medical Center. Support for the study includes American Cancer Society Research Scholar Grant RSG-17-022-01-CPPB, Health Resources and Services Administration contract 234-2005-37011C, National Institutes of Health grant DK078772, National Science Foundation award 1722665, and the MGH Research Scholars Program.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”

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Have your say: contribute to the UN’s work to end TB, HIV and viral hepatitis in the WHO European Region http://www.eatg.org/news/have-your-say-contribute-to-the-uns-work-to-end-tb-hiv-and-viral-hepatitis-in-the-who-european-region/ Fri, 15 Dec 2017 22:59:37 +0000 http://www.eatg.org/?post_type=news&p=7078 The WHO Regional Office for Europe is seeking input on a United Nations (UN) common position paper on ending tuberculosis (TB), HIV and viral hepatitis through intersectoral collaboration, drafted in collaboration with sister UN agencies. The consultation survey will remain available until 11 January 2018 and can be accessed here.

The paper illustrates the factors outside the health sector that influence the ongoing epidemics of TB, HIV and viral hepatitis in the WHO European Region, and sets a vision for cross-sectoral actions, highlighting principles and directions. It also looks at possible and practical means of implementation and evaluation.

The five questions in the survey focus on the sections that concern shared principles, directions for action, and accountability and operationalization.

The survey will take approximately 10 minutes and is anonymous.

The UN common position paper is a product of the Issue-based Coalition on Health and Well-being, a partnership initiative led by WHO Regional Office for Europe to support the achievement of UN Sustainable Development Goal (SDG) 3 and of the health-related targets present in other SDGs.

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Inclusive criteria, generic drugs effective for HCV in limited resource nations http://www.eatg.org/news/inclusive-criteria-generic-drugs-effective-for-hcv-in-limited-resource-nations/ Tue, 12 Dec 2017 20:36:10 +0000 http://www.eatg.org/?post_type=news&p=7055 Researchers from the University of Cairo analyzed the rates of sustained virologic response among patients with hepatitis C in Egypt since the introduction of direct-acting antivirals to share data on the planning and prioritization of treatment in a nation with limited resources and high prevalence of HCV.

Prioritization based on fibrosis stage was not effective and enrollment for DAA therapy increased once the program included all stages of fibrosis. Additionally, the availability of generic drugs reduced costs and helped increased enrollment in the program.

“Despite these successes and the high SVR rate with most treatment regimens used, the program faced several difficulties that caused backlogs and delays, were not anticipated, and had to be managed as they occurred,” Aisha Elsharkawy, MD, from the University of Cairo, and colleagues wrote. “The Egyptian national program for treating hepatitis C can thus send several messages and share several limitations with countries of similar settings. Avoiding them when starting treatment programs in similar settings would save time and resources.”

The study included 337,042 patients with hepatitis C who received treatment between October 2014 and March 2016. The researchers included patients with hepatitis B or HIV coinfection, those who had undergone liver transplantation, and those with severe extrahepatic manifestations.

In their analysis, the researchers categorized patients into three equal time periods of 6 months according to the standard DAA therapy in use:

Cohort 1: 120,407 patients treated between October 2014 and March 2015;

Cohort 2: 159,750 patients treated between April 2015 and 2015; and

Cohort 3: 56,885 patients treated between October 2015 and the end of March 2016.

From October 2014 to May 2015, the available DAA regimens included sofosbuvir with ribavirin or sofosbuvir with ribavirin and pegylated interferon.

“With limited financial resources, limited initial supply of medication, and limited capacities of treatment centers to handle the huge number of patients living with the diagnosis,” the researchers wrote, “there was a need to initially prioritize treatment to include patients with advanced fibrosis and to postpone treatment for patients with less advanced disease.”

After May 2015, however, it became apparent that the prioritization of patients by fibrosis stage resulted in a large backlog of patients waiting for treatment. This led to administrative and moral difficulties, according to the researchers. Additionally, more drugs became available, including simeprevir and daclatasvir.

At this time, the program shifted to include all patients regardless of fibrosis stage. The new protocol categorized patients into two groups. “Easy-to-treat” patients without cirrhosis who were treatment naive received sofosbuvir and daclatasvir, whereas “difficult-to-treat” patients with cirrhosis and treatment experience received sofosbuvir and daclatasvir with ribavirin.

Final outcomes

Patients in cohort 1 were more likely to have received treatment with interferon than those in cohort 2 or 3 (18.9% vs. 6.8%; P < .01) and had higher levels of baseline alanine aminotransferase, aspartate aminotransferase, bilirubin, international normalized ratio and alpha-fetoprotein, and lower levels of platelets and albumin.

The SVR rate for all 337,042 treated patients was 28%. The rate increased from 15.1% in cohort 1 to 67.7% in cohort 3. Among a subgroup analysis of 94,258 patients treated in the two months after cohort 3’s time period, the SVR rate increased up to 75.4%.

The combination of sofosbuvir with ribavirin for 24 weeks had the lowest SVR rate at 12 weeks (82.6%) compared with sofosbuvir with ribavirin and PEG-IFN (93.3%), sofosbuvir with simeprevir (97.4%), sofosbuvir with daclatasvir (97.8%) and sofosbuvir with daclatasvir and ribavirin (97.6%).

The presence of diabetes, hypertension, HBV surface antigen or HIV coinfection, and history of hepatocellular carcinoma, chemotherapy or liver transplantation did not impair therapy response.

The researchers also observed that generic drugs correlated with higher SVR rate (98.4%) compared with the brand medications.

“Cheap generic alternatives are effective, were the reason for the large number of patients treated, and are a suitable option for countries of similar limited resources,” the researchers wrote.

“The program has been cost-driven, and guidelines were repeatedly modified with the availability of cheaper and generic medications. The cost of diagnostics, on the other hand, remains an important part of the total cost to the program, and will remain a problem as long as there are no cheaper or generic alternatives,” Elsharkawy and colleagues concluded. “Simplifying the current testing schedule is essential and will result in significant saving.”

Elsharkawy A, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.11.034.

By Talitha Bennett

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Harm reduction approaches predicted to reduce rates of new hepatitis C infection for people who inject drugs http://www.eatg.org/news/harm-reduction-approaches-predicted-to-reduce-rates-of-new-hepatitis-c-infection-for-people-who-inject-drugs/ Mon, 11 Dec 2017 21:45:24 +0000 http://www.eatg.org/?post_type=news&p=7021 A combination of providing clean needles and syringes and offering safer oral therapy, such as methadone, reduced the predicted risk of becoming infected with hepatitis C virus by 71%. Providing both services to people who inject drugs was likely to be cost-effective and has the potential to be cost-saving in some parts of the UK, depending on the size of the local population of people who inject drugs and underlying rates of infection.

Current services are estimated to save up to £54 million in costs of treating hepatitis C infection. This is in addition to the savings made from reducing the incidence of HIV infections. This study suggests that if such programmes are decommissioned, the number of new hepatitis C infections would at least double.

This NIHR-funded study combines a review of international evidence with analysis of current usage data from three UK sites, and models the impact of withdrawing or increasing services. The evidence is based on observational studies and modelling so should be interpreted with caution. However, given the nature of the subject, it would be difficult to gather higher quality evidence.

Why was this study needed?

In 2015/16, nearly 150,000 adults seeking help for substance misuse were opiate dependent. About a quarter of those seeking help for opiates were currently injecting. Amongst those injecting almost half have hepatitis C – a virus that, if left untreated, can cause cirrhosis and liver failure. The risk of contracting this blood-borne virus increases with reuse of contaminated needles or syringes.

Key interventions to reduce infections are needle and syringe programmes which minimise the use of contaminated equipment, and opioid substitution therapy. Opioid substitutes are oral medications such as methadone, buprenorphine and naloxone which are usually given under supervision and provide a route to stopping or reducing the frequency of injecting.

Although there is good evidence that these interventions have an impact on the spread of HIV, there is little evidence of their impact on the incidence of hepatitis C. This study aimed to fill that knowledge gap, as well as assess costs and cost-effectiveness of these ‘harm reduction’ programmes.

What did this study do?

This research included a systematic review and meta-analysis of 28 studies reporting the effects of needle and syringe programmes and opioid substitution therapy on rates of new hepatitis C infection. The researchers also analysed data from eight surveys of a total of 14,734 people to calculate the risk of infection according to the level of exposure (how often people used the clean equipment or substitutes). Finally, data on the costs of needle and syringe programmes from three cities in the UK were collated for the financial year 2013-14. A mathematical model was used to estimate the effect on the spread of hepatitis C infection if interventions were withdrawn or increased, and to assess their cost-effectiveness.

Only five of the 28 studies in the review were from the UK, and the majority were observational studies, rated as low-quality evidence. Other limitations include the difficulty in measuring how often people swapped their injecting equipment.

What did it find?

  • Oral substitutes reduced the risk of being infected with hepatitis C by 50% after taking into account numerous potential confounding factors (adjusted rate ratio [aRR] 0.50, 95% confidence interval [CI] 0.40 to 0.63); 12 studies, 6,234 participants). For example, this would reduce a base line rate of 20 new hepatitis C infections per 100 users per year to 10. In other words, 10 people would need to enrol in opioid substitution for a year for one case of hepatitis C to be prevented.
  • According to European studies, mostly in the UK, when people used clean needles each time they injected (100% coverage) there was a 56% reduction in the risk of hepatitis C infection (RR 0.44, 95% CI 0.24 to 0.80; four studies, 3,994 participants). Modelling suggests that increasing the coverage of exchange programmes from existing low rates so that 80% of injections are with a clean needle/syringe, could decrease the number of new hepatitis C infections overall by 10 to 26% by 2031.
  • A combination of high usage of exchange programmes and oral substitutes resulted in a 71% reduction in the risk of hepatitis C infection (RR 0.29, 95% CI 0.13 to 0.65; four studies, 3,360 participants).
  • Costs of the exchange programmes vary around the UK, but are highly likely to be cost-effective at any willingness-to-pay threshold and were found to be cost-saving in some areas. It was estimated that maintaining current services could save up to £54 million in costs of treating hepatitis C. There was insufficient cost data to assess the cost-effectiveness of opioid substitution.
  • The modelling suggests that removing either or both harm reduction schemes would lead to an increase in hepatitis C infections over the next 15 years. It predicted that removing opioid substitution (current coverage 81%) and needle exchange (current coverage 56%) from Bristol would increase annual hepatitis C infection incidence by 329% (95% credible interval 110% to 953%) by 2031, and at least double the number of new infections.

What does current guidance say on this issue?

NICE’s 2014 guideline on needle and syringe programmes recommends that a mix of services should be provided to meet local needs. These services should be coordinated so that testing for hepatitis B and C is available to everyone who uses a needle and syringe programme. It also says that services offering opioid substitution should make needles and syringes available to their service users.

What are the implications?

Needle and syringe exchanges and opioid substitution are likely to prevent considerable rates of hepatitis C infection in the UK, particularly when the services are offered together. Needle and syringe exchange appears to be cost-effective, especially if considering the health gains from preventing HIV transmission too. Although the evidence is from observational studies, and the extent of the benefit might uncertain, the nature of the topic makes it difficult to gather evidence in any other way and compared to the cost of treating the consequences of hepatitis later, seems good value.

NICE guidance already suggests that needles and syringes should be offered with opioid substitution. This study strengthens those recommendations and could inform future updates. Barriers preventing these services being offered together need to be examined.

Citation and Funding

Platt L, Sweeney S, Ward Z, et al. Assessing the impact and cost-effectiveness of needle and syringe provision and opioid substitution therapy on hepatitis C transmission among people who inject drugs in the UK: an analysis of pooled data sets and economic modelling. Public Health Res. 2017;5(5).

This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme (project number 12/3070/13).

Bibliography

Health and Safety Executive. Hepatitis C virus (HCV). London: Health and Safety Executive.

NHS Choices. Hepatitis C. London: Department of Health; updated 2015.

NICE. Drug misuse in over 16s: opioid detoxification. CG52. London: National Institute for Health and Care Excellence; 2007.

NICE. Needle and syringe programmes. PH52. London: National Institute for Health and Care Excellence; 2014.

Public Health England. Adult substance misuse statistics from the National Drug Treatment Monitoring System (NDTMS); 1st April 2015 to 31st March 2016. London: Public Health England; 2016.

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Liver cancer incidence after HCV therapy linked to risk factors, not treatment http://www.eatg.org/news/liver-cancer-incidence-after-hcv-therapy-linked-to-risk-factors-not-treatment/ Sun, 10 Dec 2017 20:55:31 +0000 http://www.eatg.org/?post_type=news&p=7008 Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline.

“There was no increased risk for HCC as a result of having received DAA therapy whatsoever,” Raymond T. Chung, PhD, director of Hepatology and Liver Center at Massachusetts General Hospital, told Healio Gastroenterology and Liver Disease. “The risk was related to their preexisting likelihood of developing HCC. The fact that HCC developed post-DAA, we think, is more likely to be an accident of timing than the idea that it’s related to receipt of DAA — these persons were at risk for HCC whether they received DAAs or not.”

“The initial reports put physicians into a state of concern about treating such patients,” Chung continued, “but ours and several other studies all align in the respect that the DAAs themselves do not appear to be independently associated with an increased risk for HCC.”

Chung and colleagues conducted a retrospective study using patient data from the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database to assess the development of incident HCC 3 months or more from baseline.

The 17,836 patients with HCV included in the study had previously received treatment with pegylated interferon and ribavirin, DAAs, or were untreated.

Patients treated with DAAs received one of the following with ribavirin: Harvoni (sofosbuvir/ledipasvir, Gilead Sciences); combination Olysio (simeprevir, Gilead Sciences) and Sovaldi (sofosbuvir, Gilead Sciences); Viekira Pak (ombitasvir/paritaprevir/ritonavir; dasabuvir, AbbVie); or combination sofosbuvir and daclatasvir.

Most patients were men and had clinically similar median HCV RNA levels and BMI. Compared with patients treated with interferon, those treated with DAAs were significantly older (62 vs. 54 years; P < .01), more often had cirrhosis (19.9% vs. 13.1%; P < .01) and diabetes (30.9% vs. 17.6%; P < .01), had higher median alpha-fetoprotein levels (4.3 vs. 3.2 IU/mL; P < .01) and statin use (33% vs. 17.7%; P < .01), and higher rates of sustained virologic response (96.2% vs. 66.6%; P < .01).

During a mean follow-up of 2,719.2 days for IFN-treated patients and 396.4 days for DAA-treated patients, the researchers observed 196 and 50 incident cases of HCC, respectively.

HCC incidence

Chung and colleagues performed their primary analysis in patients with cirrhosis and found no significant difference in HCC incidence between those who received DAA or IFN therapy. However, untreated patients with cirrhosis had a significantly higher rate of HCC compared with treated patients (45.31 per 1,000 person-years; P = .03).

Similarly, treated patients with cirrhosis who did not achieve SVR had higher rates of HCC, though this did not differ between treatment with DAAs or IFN. Treated patients with cirrhosis who achieved SVR had a significantly lower risk for HCC (P = .0004).

Among patients with FIB-4 data within 12 months of baseline, DAA treatment correlated with a significantly lower HCC rate compared with IFN among patients with cirrhosis (17.9 vs. 31.99 per 1,000 person-years; P < .01), though not between treatment groups in patients who achieved SVR.

“It’s always important to stage our patients with hepatitis C as they embark on a course of antiviral therapy because of the implications for what follow-up care those patients require,” Chung said. “Patients with advanced fibrosis require continued screening for HCC, whether they get treated with DAAs or not.”

“Clinicians should not be deterred in treating those patients with advanced fibrosis because they are already in a state of advanced liver disease,” Chung continued. “This is a group that most merits therapy to interrupt their natural history.”

During an analysis of all patients who achieved SVR with DAA therapy, the researchers found a higher rate of HCC compared with IFN-treated patients (7.41 vs. 3.48 per 1,000 person-years; P < .01). However, HCC rates between treatment groups did not differ among those who did not achieve SVR.

Another subgroup analysis of HCC rates in patients treated with IFN-free DAA therapy showed that patients treated with simeprevir or sofosbuvir had higher baseline rates of cirrhosis compared with those treated with IFN (39.6% vs. 13.1%; P < .01) or sofosbuvir/ledipasvir (39.6% vs. 18.9%; P < .01).

Final analysis

Among patients with cirrhosis, DAA treatment did not correlate with a higher risk for HCC compared with IFN treatment (HR = 1.07; 95% CI, 0.55-2.08).

The risk for incident HCC was higher, however, among patients with known HCC risk factors such as older age (HR =1.76 per 10-year increase; 95% CI, 1.26-2.46) and AFP levels higher than 20 at baseline (HR = 4.1; 95% CI, 2.75-6.1). Statin use correlated with a lower risk for HCC (HR = 0.5; 95% CI, 0.31-0.8), whereas PPI use correlated with a higher risk (HR = 1.65; 95% CI, 1.07-2.55).

There was no difference in HCC-free survival between the two treatment groups.

While successful SVR did not correlate with a significantly lower HCC rate in the primary analysis, the researchers found that SVR was statistically significant after a multivariable analysis that limited the baseline FIB-4 to within a 12-month period prior to baseline (HR = 0.6; 95% CI, 0.38-0.93).

“We don’t want to dissuade physicians from treating people with advanced fibrosis and cirrhosis who have hepatitis C from getting therapy which can provide numerous downstream benefits in terms of interrupting and essentially stopping disease progression unleashed by hepatitis C in the first place,” Chung concluded. “We should overcome any hesitation in treating this group of patients who definitely warrant treatment.”

Li DK, et al. Hepatol. 2017;doi:10.1002/hep.29707.

By Talitha Bennett

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HCV antiviral properties found in South American plant compounds http://www.eatg.org/news/hcv-antiviral-properties-found-in-south-american-plant-compounds/ Sun, 10 Dec 2017 20:50:09 +0000 http://www.eatg.org/?post_type=news&p=7009 Compounds derived from a South American plant showed antiviral properties in a study investigating the substances’ effects on the hepatitis C virus (HCV).

The findings support that the natural flavonoid isolates from Brazilian plants possess anti-HCV potential, corresponding author Ana Carolina Gomes Jardim, PhD, told MD Magazine.

“They could represent different approaches or be used as template to the development of drugs for future HCV therapy,” Jardim said.

Jardim, along with biologists, chemists and pharmacists from Brazil and the UK, investigated 2 flavonoids found in Pterogyne nitens, a member of the legume family. P. nitens is commonly known as cocal, bálsamo, and tipa colorado in its native Brazil, Paraguay, Bolivia and Argentina.

Previous studies investigating these flavonoids — called sorbifolin and pedalitin — have shown that they possess antiproliferative effects against melanoma cells. The compounds also have demonstrated antioxidant and antifungal activity, the authors said.

“We showed that these 2 compounds already previously described in the literature posses anti-HCV activity,’’ Jardim, Professor in Virology, Federal University of Uberlândia, in Minas Gerais, Brazil, said. “This was the first description of antiviral activity for these flavonoids.”

Flavonoids represent an important class of compounds in medical research. The substances are produced by plants as a response to microbial infections. Epigallocatechin derived from green tea and naringenin from grapefruit have been reported to possess antiviral activities, including against HCV.

Citing promising past research and the cost and drawbacks of current HCV therapies, the team set out to investigate the potential impact of the 2 P. nitens compounds on the HCV replication cycle.

Researchers from the Federal University of Uberlandia and São Paulo State University in Brazil, and the University of Leeds in the UK contributed to the work.

The team used dried P. nitens leaves to extract the compounds for study. After testing for potential toxicity, the researchers found that sorbifolin inhibited hepatitis C virus entry up to 45% and pedalitin inhibited entry by 78.7%.

Pedalitin blocked entry by both direct action on the virus particles and interference with the host cells. The activity of sorbifolin was restricted to its viruscidal effect, the team found.

“The results showed that flavonoids from P. nitens inhibited HCV entry in vitro,’’ researchers wrote. “Further analyses are necessary to clarify the mechanisms of how these flavonoids act against HCV infection.’’

Neither flavonoid had an effect HCV replication or release, the team found.

“We came to this conclusion after biochemical studies and several antiviral assays, which allowed us to understand and evaluate the potential of these compounds,’’ Jardim said. “Our findings support that the natural flavonoids isolates from Brazilian plants possess anti-HCV potential.’’

While the results are promising, more tests are needed to ensure that these compounds can be used to help patients with HCV infections, Jardim said.

“These findings strengthen the theory that natural compounds may be an alternative pathway in the treatment of hepatitis C,’’ she said. “The benefits are not immediate but can help to improve future therapy against HCV.’’

The study, “Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry,” was published online in Nature last month.

By Gail Connor Roche

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Resistance analysis of Epclusa shows patients may retreat with sofosbuvir http://www.eatg.org/news/resistance-analysis-of-epclusa-shows-patients-may-retreat-with-sofosbuvir/ Thu, 07 Dec 2017 19:00:20 +0000 http://www.eatg.org/?post_type=news&p=6987 Treatment with Epclusa for 12 weeks resulted in high sustained virologic response rates among patients with hepatitis C genotypes 1 through 6, irrespective of baseline NS5A resistance-associated substitutions, according to recently published data.

The researchers detected NS5A inhibitor resistance, but not resistance to sofosbuvir, in the few patients who did not achieve SVR.

“Treatment with [Epclusa] for 12 weeks was effective across highly diverse HCV subtypes,” Christophe Hézode, MD, PhD, from the Université Paris-Est, France, and colleagues wrote. “Most of the few patients who experienced virologic failure after treatment with [Epclusa] for 12 weeks had single class resistance to NS5A inhibitor velpatasvir, but not to the NS5B inhibitor sofosbuvir allowing for a possible retreatment with sofosbuvir-containing regimens.”

The researchers conducted resistance analyses of six phase 3 clinical trials of Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) for 12 weeks in a total of 1,778 patients with chronic HCV genotypes 1 through 6. Trials included the ASTRAL 1, 2, 3 and 5 studies and POLARIS-2 and POLARIS-3 studies.

The overall SVR across the studies was 98.9%. The SVR rates by genotype were 99% for genotype 1, 100% for genotype 2, 97.5% for genotype 3, 99.5% for genotype 4, and 100% for genotypes 5 and 6.

The overall prevalence of NS5A RASs was 28% in patients with available NS5A sequencing data (n = 1773). The lowest prevalence was 9% in patients with genotype 5 and the highest prevalence was 61% among patients with genotype 2.

Among patients with genotypes 1a, 1b, 2, 4, 5 or 6, the presence of NS5A RASs at baseline had no impact on SVR rate.

Twelve percent of patients with genotype 3 had NS5A RASs at baseline. Compared with those without NS5A RASs at baseline, patients with genotype 3 and NS5A RASs had a lower SVR rate at 12 weeks (93% vs. 98%).

Prevalence of baseline NS5A velpatasvir-specific RASs among the whole cohort was 8% (n = 138) with the lowest prevalence in patients with genotype 5 (0%) and the highest prevalence among patients with genotype 6 (52%).

“The lower prevalence of NS5A velpatasvir-specific RAS compared to NS5A class RASs is due to the improved resistance barrier of velpatasvir,” according to the researchers. The SVR rates for patients with genotypes 1 through 6 and velpatasvir-specific RASs ranged from 93% to 100% compared with 98% to 100% in patients without velpatasvir-specific RASs.

Twenty of the 1,778 patients treated with sofosbuvir/velpatasvir for 12 weeks did not achieve SVR. Of those, seven had HCV genotype 1, 12 had genotype 3, and one had genotype 4.

Hézode C, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.11.032.

By Talitha Bennett

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Elevated HBV surface antigen, viral load increases liver cancer risk http://www.eatg.org/news/elevated-hbv-surface-antigen-viral-load-increases-liver-cancer-risk/ Thu, 07 Dec 2017 18:57:33 +0000 http://www.eatg.org/?post_type=news&p=6983 Elevated levels of hepatitis B DNA and hepatitis B surface antigen correlated significantly with an increased risk for liver cancer, according to recently published data.

“Increasing evidences have suggested that a lower HBsAg level is associated with better clinical outcomes, including a higher likelihood of HBsAg loss, lower risk of [hepatitis B e antigen-negative] hepatitis, cirrhosis and [hepatocellular carcinoma],” the researchers wrote. “Clinical therapy of [chronic HBV] to simultaneously lower serum levels of both HBV DNA and HBsAg may be suggested to lower the risk of liver cancer, especially for those high-risk persons.”

The researchers conducted a nested case-control study within two large population-based cohorts in Shanghai to prospectively assess the risk for liver cancer by combining quantitative HBsAg level and viral load.

The study comprised 211 patients with liver cancer and 221 controls who were seropositive for HBsAg and followed for cancer occurrence every 2 to 3 years from 2000 to 2011.

Compared with controls, patients with liver cancer had lower family income (P = .05) and education level (P < .01), less vegetable intake (318.2 vs. 361.2 g/day; P = 0.2), and were more likely to have a history of chronic liver disease (48.34% vs. 15.84%; P < .01), family history of liver cancer (15.17% vs. 6.33%; P < .01), and a positive HBeAg status (37.91% vs. 5.88%; P < .01).

In three adjusted models, risk for liver cancer correlated positively with increased levels of HBV DNA (all, P < .01) and HBsAg (P < .01 to P = .03) in dose-response manners.

Compared with patients with HBV DNA less than 2,000 IU/mL, liver cancer risk increased among those with HBV DNA between 2,000 IU/mL and 19,999 IU/mL (OR = 2.11; 95% CI, 0.99-4.5) and those with HBV DNA higher than 20,000 IU/mL (OR = 3.12; 95% CI, 2.19-4.44).

Similarly, compared with patients with HBsAg levels of 0.05 IU/mL to 99 IU/mL, liver cancer risk increased among those with HBsAg levels of 100 IU/mL to 999 IU/mL (OR = 1.82; 95% CI. 0.9-3.68) and those with HBsAg levels higher than 1,000 IU/mL (OR = 2.21; 95% CI, 1.1-4.43).

The researchers stratified HBsAg cut-off levels by HBV DNA for liver cancer risk. Among patients with HBV DNA less than 2,000 IU/mL, those with HBsAg levels of 100 IU/mL or higher (OR = 1.98; 95% CI, 0.96-4.11) and those with HBsAg levels of 1,000 IU/mL and higher (OR = 1.05; 95% CI, 0.42-2.59) both had an increased risk for liver cancer.

Additionally, among patients with HBV DNA higher than 2,000, liver cancer risk increased among those with HBsAg levels higher than 100 IU/mL (OR = 3.72; 95% CI, 1.17-11.82) compared with less than 100 IU/mL and among those with HBsAg levels higher than 1,000 IU/mL (OR = 2.6; 95% CI, 1.11-6.05) compared with those with less than 1,000 IU/mL.

“We observed a positive correlation between HBV DNA and HBsAg levels,” the researchers concluded. “Previous studies indicated that the correlation changed during the natural history of HBV infection, higher at HBeAg-positive phase, lower at HBeAg-negative phase and the lowly replicative phase, which was consistent with our findings.”

Yang Y, et al. J Gastroenterol Hepatol. 2017;doi:10.1111/jgh.14032.

By Talitha Bennett

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New clinical data on RNAi therapy in hepatitis B patients http://www.eatg.org/news/new-clinical-data-on-rnai-therapy-in-hepatitis-b-patients/ Wed, 06 Dec 2017 20:58:57 +0000 http://www.eatg.org/?post_type=news&p=6975 Arrowhead presents new clinical data demonstrating a sustained host response in hepatitis B patients following RNAi therapy

— Up to 5.0 log10 reduction in HBsAg observed; data presented at HEP DART 2017 —

PASADENA, Calif., Dec 6, 2017 — Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) presented new data from the company’s Phase 2 clinical study in patients that received multiple doses of ARC-520, the company’s prior generation RNAi-based clinical candidate against chronic hepatitis B infection (HBV). A maximum reduction from baseline in HBV surface antigen (HBsAg) of 5.0 log10 was achieved seven months following the administration of the last dose of ARC-520, with the lowest absolute level observed being just above the lower limit of HBsAg quantitation. These data, presented at the 22nd biennial HEP DART meeting held in Kona, Hawaii, from Dec. 3-7, indicate that multiple doses of an RNAi-based therapy may lead to a host response that is sustained after therapy is concluded.

Bruce D. Given, M.D., chief operating officer and head of R&D for Arrowhead Pharmaceuticals, said: “We believe that achieving a functional cure of chronic hepatitis B infection will require a sustained host response, which is likely to be immune mediated. In our Phase 2 study of ARC-520, multiple patients saw continued reductions in key HBV markers long after ARC-520 treatment ceased. These data represent the first clinical evidence that an RNAi-based approach can lead to the type of favorable sustained host response that we have always believed is possible. Achieving this result with ARC-520, which was not designed for activity against HBV s-antigen produced by integrated DNA, provides us with further confidence that our new RNAi-based compound, ARO-HBV, which is designed to silence the production of all HBV gene products, including transcripts derived from integrated DNA, has a good chance of being a backbone therapy for combinations intended to cure chronic HBV.”

In an oral presentation titled, “Looking Back to Move Forward – Designing Next Gen RNAi for HBV,” Dr. Given showed key evidence for the first time that 2 of 3 (66.7%) HBV e-antigen (HBeAg) positive patients and 2 of 5 (40%) HBeAg negative patients treated with an RNAi-based therapy achieved a sustained host response off therapy. This was characterized by continued reduction of multiple HBV viral markers, including HBsAg, and coinciding with an increase in circulation of liver enzyme alanine aminotransferase (ALT), indicative of host response. The new data from Heparc-2001, the company’s Phase 2 open-label extension study of ARC-520 in combination with entecavir in 8 patients, follows patients over 7 months after the last ARC-520 dose was administered, which is the last time point currently available.

In the 4 patients that appeared to have a sustained host response, observed reductions in HBsAg were 5.0, 3.1, 2.4, and 0.6 log10 from baseline. In addition, these patients achieved absolute levels of HBsAg of 58, 2.6, 0.36, and 0.051 IU/ml. The lower limit of quantitation for this measurement of HBsAg is 0.05 IU/ml, below which would be deemed seroclearance. These patients also achieved reductions in HBV DNA to below the level of quantitation, and deep reductions in core-related antigen (HBcrAg), and HBeAg, with many at or below their respective lower limits of quantitation.

Dr. Given also presented select preclinical data on ARO-HBV, a new therapy for patients with chronic HBV that utilizes the company’s next generation Targeted RNAi Molecule (TRiM™) platform. Notably, 3 doses of ARO-HBV in wild type pHBV mice led to reductions in HBV DNA of 3.44 log10 and both HBsAg and HBeAg dropped below the lower limit of quantitation (reductions of greater than 3.0 log10 and greater than 2.2 log10, respectively).

In addition, Arrowhead created a mutated pHBV mouse model that eliminates the HBx trigger site to simulate HBV patients with high levels of integrated HBV DNA relative to cccDNA. In this model, a single dose of ARO-HBV led to a reduction in HBsAg of 2.95 log10. The duration of effect was long, with a HBsAg reduction of approximately 2.0 log10 still observed 8 weeks after the dose.

ARO-HBV is designed to silence the production of all HBV gene products, including transcripts derived from integrated DNA, with the goal of getting to a level where patients’ immune systems can reconstitute, leading to a sustained host response and ultimately a functional cure. Arrowhead’s learnings from multiple clinical studies of prior generation compounds, ARC-520 and ARC-521, and the extensive non-clinical research completed in multiple species, including long-term treatment of chimpanzees, have guided the rapid development of ARO-HBV. The results presented with respect to ARC-520 are not necessarily predictive of ARO-HBV results.

GLP-toxicology studies are being conducted and Arrowhead is manufacturing the drug supply necessary to begin clinical studies of ARO-HBV. The company anticipates filing a Clinical Trial Application by the second quarter of 2018.

Slides from Dr. Given’s presentation may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/alerts.cfm.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

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Dibenzoazepine defender: Drug found to be effective against resistant hepatitis C http://www.eatg.org/news/dibenzoazepine-defender-drug-found-to-be-effective-against-resistant-hepatitis-c/ Wed, 06 Dec 2017 19:53:07 +0000 http://www.eatg.org/?post_type=news&p=6974 Osaka University researchers identify class of chemicals that can combat resistant strains of the hepatitis C virus, as well as parasites that cause malaria and toxoplasmosis

Osaka, 2017-11-28 – Hepatitis C is caused by a highly infectious virus affecting millions across the globe and can lead to a variety of liver ailments. While the hepatitis C virus (HCV) can sometimes be fought off and cleared by the immune system during the first few months of acute infection, up to 80% of those with HCV develop a chronic infection. This can lead to serious liver illnesses, including inflammation, cirrhosis, and hepatocellular carcinoma – the third leading cause of cancer death worldwide.

While highly effective treatments for HCV have become available in recent years, drug-resistant viral strains can still lead to treatment failure for a sizable proportion of patients. Now, in a recent study published in PNAS Plus, a compound has been reported that may eventually prove effective against drug-resistant HCV.

A team of researchers centered at Osaka University infected human liver cells with HCV, then treated the infected cells with different drugs to see which might prevent the virus from spreading. One compound, innocuously named YO-01027, stood out above the rest.

“For HCV to propagate in a host cell, the proteins that make up the virus particle need to be cleaved into their mature form,” lead author Junki Hirano explains. “We tested several compounds we thought may inhibit this cleavage process, and found that YO-01027 prevents a key HCV protein from undergoing cleavage and maturation. We correspondingly found the drug is very effective at suppressing HCV infection.”

Importantly, resistant strains of HCV did not emerge over time when the infected cells were treated with YO-01027. This may owe to the unique way the compound prevents the virus from maturing.

Patients with HCV are currently given direct-acting antivirals, which (as their name suggests) directly target and disrupt HCV proteins themselves. The drug tested in this study, however, inhibits one of the host cell’s proteins – signal peptide peptidase (SPP) – that HCV hijacks during an infection.

“Direct-acting antivirals have made tremendous progress in treating HCV,” corresponding author Yoshiharu Matsuura explains. “The difficulty is that HCV shows quite high genetic diversity, even within a single patient. Antivirals produce a strong selective pressure that can cause HCV strains with resistant forms of the target protein to spread. By inhibiting the host’s own SPP protein, we can largely bypass this selection problem.”

Through a combination of computer simulations and in vitro tests, the researchers identified the chemical signature of YO-01027 responsible for its effectiveness, a structure called dibenzoazepine. With this and other molecular details in hand, the researchers may now be able to modify YO-01027 and other dibenzoazepine-containing drugs to develop novel therapies for drug-resistant HCV – and, serendipitously, to potentially develop therapies against a variety of other diseases.

“Now that we know some of the key structural features that make YO-01027 effective at inhibiting SPP, we can start the chemical fine tuning,” Matsuura adds. “Ultimately, the goal is to make highly selective drugs to combat pathogens that need SPP to survive and spread. This includes not only viruses like HCV, but also parasites such as Plasmodium falciparum and Toxoplasma gondii that are responsible for malaria and toxoplasmosis. The possible applications are very exciting.”

To learn more about this research, view the full research report entitled “Characterization of SPP inhibitors suppressing propagation of HCV and protozoa” at this page of Proceeding of the National Academy of Sciences of the United States of America.

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Time to galvanize efforts to combat hepatitis C http://www.eatg.org/news/time-to-galvanize-efforts-to-combat-hepatitis-c/ Tue, 05 Dec 2017 22:50:22 +0000 http://www.eatg.org/?post_type=news&p=6953

In the first few years of this century, the country of Georgia, in the Caucasus region between Europe and Asia, was plagued by civil war, economic instability and a number of severe aftershocks—including a surge of hepatitis C infections. Today, its hepatitis C elimination programme, the first of its kind in Europe, is becoming an example of an effective approach to beating back the epidemic at the country level.

Georgia has the third highest hepatitis C infection rates in the world. But in working with Gilead Sciences, the producer of the drug sofosbuvir, through an innovative public-private partnership, the government has provided new treatment to 40,000 people, curing 84 percent of them. As part of this programme, which included improvements in monitoring, surveillance and screening, the country was able to gain a better understanding of the prevalence of the disease. Previous estimates were based on data captured 15 years ago.

Georgia, however, is an exception. Although we have new hepatitis C treatments that can be up to 100% effective for a 12-week course, they simply are not getting to those who need them. Why? Well for starters, more than 70% of estimated 71 million suffering with hepatitis C live in low- and middle-income countries where access to testing, let alone treatment, is limited. Hepatitis C also is a disease of poverty; the easiest ways to become infected involve sharing needles while injecting drugs or being treated with outdated medical equipment—often found in locations with underfunded health systems. Intravenous drug users do not often have consistent access to medical services—even for a three-month stretch—and underfunded health systems do not often provide consistent care.

The initial, extremely high price of new drugs has been a major barrier to access, but there are some bright spots on the horizon. Egypt, with the world’s highest hepatitis C burden, is supplying locally-produced hepatitis C drugs to its patients, and has achieved impressive coverage rates. Gilead Sciences signed licensing agreements with 11 Indian manufacturers to locally produce sofosbuvir for developing countries, and 10 generic companies are working through the Medicines Patent Pool to develop low-cost versions of Bristol-Myers Squibb’s daclatasvir, which works best when paired with sofosbuvir. One hundred and twelve countries stand to benefit from the MPP deal, one of them Indonesia. The government just approved the treatment for its 1.3 million hepatitis C patients and expects to rollout these affordable curative regimens in early 2018.

As a result of generic competition, prices are dropping. At the end of October, Médecins Sans Frontières announced it had secured a price of $120.00 for a three-month course of sofosbuvir-daclatasivr, a dramatic cut from a $147,000 price point for the medicines in 2013.

Of course, treatment gains only go so far. Without proper systems in place to prevent and detect the disease, we cannot hope to eliminate hepatitis C in this generation. Countries are making good progress in keeping blood supply safe and improving injection safety. Hepatitis C diagnostics costs such as laboratory based tests for HCV antibodies are relatively low, but they require trained personnel and modern equipment. An estimated 57 million people are unknowingly living with the disease. Reaching them must be part of an international effort to stop hepatitis C in its tracks.

The picture of hepatitis C today looks similar to that of HIV/AIDS at the end of the last century, with some remarkable differences. HIV and hepatitis C affect marginalized populations, and both are challenging to pinpoint, with silent infections that can lie dormant for decades. In both HIV and hepatitis C, new better regimens revolutionized the field—from HAART for HIV in the mid-1990s to hepatitis C direct-acting antivirals of today. However, it took between five and 10 years before new HIV drugs reached low and middle-income countries as quality-assured generics. In contrast, countries like Egypt, Pakistan and India are already benefiting from low-cost options of new hepatitis C technologies.

While there is no cure for HIV, which remains a chronic illness, we have at our disposal effective remedies for hepatitis C if we can deliver them to all patients in need. Unlike HIV treatment which requires a life-time commitment, the battle against hepatitis C can be won over the course of a season. Community involvement and commitments from national governments to eliminate the disease through coordinated prevent, screen, treat and monitor programmes are the way forward. If countries like Georgia are any proof, this is doable.

By Marie-Paule Kieny
Chair of the Medicines Patent Pool Governance Board

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High treatment uptake is possible for HCV patients coinfected with HIV http://www.eatg.org/news/high-treatment-uptake-is-possible-for-hcv-patients-coinfected-with-hiv/ Tue, 05 Dec 2017 20:17:33 +0000 http://www.eatg.org/?post_type=news&p=6955 The current gold standard for treatment of chronic hepatitis C virus (HCV) infection is direct-acting antiviral (DAA) therapy, which has proven to be safe and highly efficacious. However, DAA therapy is quite costly and this limitation has led to its use being restricted in many countries.

In the Netherlands, DAA regimens became available initially for patients with severe liver fibrosis as well as patients coinfected with HIV. In a study published by the Oxford University Press, lead co-investigators, Anne Boerekamps, PhD, and Astrid Newsum along with their colleagues examined HCV treatment uptake in HCV and HIV coinfected patients in the Netherlands.

The study utilized the AIDS Therapy Evaluation in the Netherlands (ATHENA) database which includes information on more than 98% of the HIV-positive patients in care in the Netherlands. There are 26 designated treatment centers in the Netherlands which provide care for HIV patients. The ATHENA cohort is responsible for collecting demographic and treatment data as well as data on patients coinfected with HIV and viral hepatitis. Out of the 23,574 HIV patients registered in the ATHENA cohort as of the February 1, 2017, 2503 patients had at least one positive HCV RNA test. The authors excluded patients who spontaneously cleared their HCV infection as well as patients who died or were lost to follow-up, resulting in 1471 patients who were coinfected with HIV and HCV. Ninety-percent of the patients included in the study were male and the most commonly reported route of HIV transmission was MSM (69%). In addition, HIV transmission occurred for the remaining 15% either through drug use or other routes.

Of the 1471 patients that were included in the study, 1284 had sought treatment for HCV between the years of 2000 and 2017. Out of these patients, 702 previously received or were still receiving a DAA regimen and the other 582 were treated with older HCV regimens, such as interferon-alpha.

The authors note that as of February 2017—which is only 15 months after the Netherlands made DAAs available to all chronic HCV patients—76% of patients coinfected with HIV and HCV have achieved a sustained virologic response (SVR), indicating that they were successfully treated. Furthermore, an additional 6% were expected to achieve treatment success. The authors also found that HCV cure rates were highest in the MSM category of coinfected patients.
This work demonstrates after only 15 months of unrestricted access to DAAs, a high treatment uptake is possible for patients coinfected with HIV and HCV.

One of the limitations of this study was that there was no data on patients who were lost to follow-up, which comprised 6% of the HIV and HCV coinfected patients. However, the strengths of this study lie in the use of the ATHENA cohort which is highly representative of the HIV infected patient population in the Netherlands. In addition, this work represents the first study that examined the effect on unrestricted DAA access for HIV and HCV coinfected patients. If unrestricted access is continued, it may be possible to eliminate HCV among co-infected patients in the Netherlands.

By Samar Mahmoud

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HCV patients SVR with Mavyret after previous DAA failure http://www.eatg.org/news/hcv-patients-svr-with-mavyret-after-previous-daa-failure/ Tue, 05 Dec 2017 19:20:09 +0000 http://www.eatg.org/?post_type=news&p=6956 Patients with the hepatitis C virus (HCV) who received a 16-week regimen of glecaprevir and pibrentasvir (Mavyret) achieved high sustained virologic response (SVR) rates after previous treatments had failed, new findings show.

An international team of researchers studied 91 individuals with chronic HCV — 87 with genotype 1, and 4 with genotype 4. These patients had prior failures when treated with direct-acting antiviral (DAA) therapies that consisted of at least 1 NS3/4A protease and/or NS5A inhibitor-containing medication.

With glecaprevir and pibrentasvir (G/P), the SVR rate was 89% after 12 weeks and 91% after 16 weeks. The patients received a 3-pill, once-a-day dose of 300 mg/120 mg.

“The few patients who fail a primary treatment attempt with direct acting antivirals have over a 90% chance of cure using a 16-week regimen of the newly approved glecaprevir and pibrentasvir,’’ author Fred Poordad, MD, Professor of Medicine at University of Texas Health, San Antonio, told MD Magazine. “This means we should be able to cure over 99% of all hepatitis C patients.’’

The US Food and Drug Administration (FDA) approved Mavyret on August 3 to treat adults with chronic HCV genotypes 1-6 who have no cirrhosis or mild cirrhosis and may have moderate to severe kidney disease.

Mavyret was also approved for adults with HCV genotype 1 who have undergone therapy with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor.

Previously, patients who experienced virologic failure after therapy that contained an NS5A inhibitor had limited retreatment options, the researchers wrote.

To determine the efficacy and safety of ribavirin (RBV)-free glecaprevir and pibrentasvir in this population, the team looked at individuals who had prior virologic failure on at least one NS3/4A protease and/or NS5A inhibitor-containing therapy.

Poordad explained that individuals who fail to be cured with their first attempt may have baseline resistant variants, which render the medications less effective.

“The combination of glecaprevir and pibrentasvir is a very potent, well tolerated regimen, which covers most of the resistant variants that other regimens cannot cover,” Poordad said. “Hence, failure with other regimens does not mean the patient cannot be cured. This regimen offers another hopeful option.”

Poordad noted that compliance with medications is always critical.

“Patients will fail if they do not comply with the medication regimen,’’ he said.

The researchers reported 1 treatment virologic failure and 4 relapses in the 12-week group. Those treated for 16 weeks had 4 on-treatment virologic failures, the team found.

Prior treatment history with 1 class of inhibitor (protease or NS5A) had no impact on SVR12, while prior treatment with both classes of inhibitors was associated with lower SVR12 rate, they wrote.

The most common adverse event was headache, which was experienced by at least 10% of patients.

“There were no serious adverse events (AEs) assessed as related to study drugs or AEs leading to discontinuation,’’ the researchers wrote.

Poordad said he was not surprised by the findings.

“Based on the in vitro laboratory results of the potency of the G/P regimen, I expected high cure rates in these difficult to cure patients,” he said.

G/P is an excellent option and is less costly than many regimens on the market, Poordad said.

AbbVie sponsored the study, contributed to the collection, analysis, and interpretation of data, and participated in the writing, review, and approval of the manuscript.

The study, “Glecaprevir/Pibrentasvir in Patients with HCV Genotype 1 or 4 and Prior Direct-acting Antiviral Treatment Failure,” was published online in Hepatology last month.

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Ireland not on track to eliminate hepatitis C http://www.eatg.org/news/ireland-not-on-track-to-eliminate-hepatitis-c/ Mon, 04 Dec 2017 22:33:18 +0000 http://www.eatg.org/?post_type=news&p=6931 Nov 30, 2017 – Ireland has one of the highest rates of hepatitis C infection among vulnerable groups in Europe, an international seminar in Dublin has been told.

Speaking at the seminar, Charles Gore, who is CEO of the World Hepatitis C Alliance, noted that 73% of people who inject drugs in Ireland have the virus, while 35% of homeless people here are also infected.

Hepatitis C is an infection of the liver caused by the hepatitis C virus. An estimated 30,000 people are infected, however many of these may be unaware they have the virus because they do not have any symptoms, or they have fju-like symptoms that can be mistaken for something else.

A person can become infected if they come into contact with the blood of an infected person. Drug users who share needles are at particular risk. While there is no vaccine against hepatitis C, it can be successfully treated. However, if left untreated, it can lead to significant liver damage.

Up to 20% of people with the virus will develop irreversible cirrhosis, which can result in liver failure. Those with cirrhosis also have an increased risk of developing liver cancer.

The seminar was told that there are indications that there may be up to 750 new infections of hepatitis C in the first nine months of 2017. This signals a worrying increase in the number of people contracting the virus and is already higher than 2016’s total figure of 652.

According to Mr Gore, Ireland is one of the few countries in Europe that is not on track to eliminate hepatitis C by 2030 based on current policy.

He said that drug costs for the virus could be, on average, three times the cost in the UK and he noted that other countries who are further along in this journey have secured elimination deals with drug companies. This means that pharmaceutical costs are reduced as treatment rates increase.

However, aside from prescription costs, he emphasised the importance of focusing on diagnosis, outreach, and prevention.

“Working proactively to eliminate the virus will also eliminate much of the cost associated it. People won’t get liver cancer because of the virus, they won’t be progressing to cirrhosis. There won’t be the same need for drug treatment. It makes sense, from a health and cost point of view, that Ireland sets its sights on making this disease a rare disease, moving with the rest of Europe,” Mr Gore commented.

Also speaking at the seminar, Dr Jack Lambert, a consultant in infectious diseases at the Mater Hospital in Dublin, pointed out that the Government allocates €30 million to the Hepatitis C programme, however this is mostly for the purchase of drugs.

“The money is there, that’s not the issue. What is the problem is that there is a disconnect between what needs to be done and what is being done. We, the people on the ground, need to be able to decide how the money is used. It should not be used for drug treatment almost exclusively,” he insisted.

He said that his patients need much more than just drugs, such as ‘care and outreach in homeless services, drug treatment services in methadone GP practices and peer support’.

“We’re not prioritising these and so we are not doing the right things to make elimination a reality,” he said.

Dr Lambert also pointed out that there is a discrepancy between accepted notification figures for the virus and the reality of the situation on the ground. This has led to a big gap between treatment numbers and those actually infected.

“At its lowest estimate, we have 30,000 with the virus in the country. So far we have treated over 2,000 people and we have another 1,000 left waiting to be treated. That adds up to 3,000 people. So where are the remaining 27,000? We have to seek and treat, not just wait for people to come to us,” he said.

The seminar, ‘A Vision of Elimination: Stop Hepatitis C’, was held in Buswell’s Hotel in Dublin city.

By Deborah Condon

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Ukraine: People co-infected with HIV to receive hepatitis C treatment in Mykolaiv region http://www.eatg.org/news/ukraine-people-co-infected-with-hiv-to-receive-hepatitis-c-treatment-in-mykolaiv-region/ Mon, 04 Dec 2017 20:50:40 +0000 http://www.eatg.org/?post_type=news&p=6943 Médecins Sans Frontières (MSF) has begun treatment for hepatitis C with people who are co-infected with hepatitis C and HIV in Mykolaiv region, in southern Ukraine, where prevalence of HIV is two times higher than the average across the country.

People living with HIV are extremely vulnerable to contracting the hepatitis C virus, which is the fifth leading cause of death of people living with HIV in Europe.

In a joint effort with the Ministry of Health of Ukraine and the Mykolaiv Regional Centre of Palliative Care and Integrated Services, 750 people living with HIV and hepatitis C, who are under antiretroviral therapy, will receive free effective treatment provided by MSF for chronic hepatitis C, using the medications sofosbuvir and daclatasvir. A further 250 people, consisting of those who formerly injected drugs and are on opioid substitution therapy, or are healthcare workers infected with hepatitis C, will also receive treatment.

MSF medical activity manager in Mykolaiv, Dr Marcelo C. M. Naveira, said: “There will be no true progress in the public health response to HIV/AIDS if hepatitis C-related deaths continue to affect people living with HIV.

“Stigma and discrimination directed at people who are co-infected must also be tackled. This project is meant to not only provide treatment for hepatitis C for people living with HIV, but also to improve access to medicines, and education and support for both diseases in Ukraine.”

A course of the treatment MSF is providing can be completed with oral medication in around three months, whereas for more than a decade, treatment options for hepatitis C have been restricted to 48 weeks or more. These older regimens have been known for their injections with high toxicity, severe adverse effects and poor success rates, preventing people living with HIV from receiving such treatment due to complications with antiretroviral therapy. New oral HCV treatment with sofosbuvir and daclatasvir has very few side effects and a cure rate of more than 95% after 12 weeks of treatment.

As people living with HIV worldwide have faced a battle to obtain affordable generic versions of antiretrovirals, those living with hepatitis C in Ukraine are blocked by a lack of generic versions of the most effective medications. Currently, the US pharmaceutical corporation Gilead Sciences maintain a patent monopoly on sofosbuvir in Ukraine and even went as far as to sue the government, forcing them to de-register a generic version of sofosbuvir that could have been used.

Gilead has recently announced the inclusion of Ukraine in the voluntary licence deal which would allow up to 11 Indian generic pharmaceutical companies to register the drug. However, there is still no access to affordable generic versions. Daclatasvir remains unregistered in the country.

“For many years, Gilead viewed Ukraine and many other middle-income countries having high burden of hepatitis C as commercial markets, and kept them out of any ‘access’ initiatives like voluntary licenses that would have allowed the availability of affordable generic versions in the country”, said Jessica Burry, pharmacist for MSF’s Access Campaign. “Finally, after considerable pressure, Gilead has eventually caved in and included Ukraine in the territory of their licence with generic companies. We really hope that the generic companies will start applying for registration soon in Ukraine resulting in competition, which would enable the Ukrainian Government to negotiate and bring the prices down to as low as US$100.”

Patients in MSF’s programme will also be supported with counselling and health education, in order to improve adherence to treatment and help them manage social issues as a result of their diagnosis. By providing information about hepatitis C and strengthening patients’ skills on seeking health services, MSF hopes will it be possible to overcome stigma and properly address patients’ needs.

When untreated, hepatitis C can lead to liver failure and liver cancer – complications that kill more than 700,000 people each year worldwide and symptoms of the virus may not display until it has reached a chronic stage. For people living with HIV, the disease progression is faster and time is vital in diagnosing hepatitis C.

MSF has also provided highly advanced diagnostic equipment to the centre in Mykolaiv, where testing began in November.

At the Mykolaiv Regional Centre of Palliative Care and Integrated Services, out of 1,940 people presenting co-infection of HIV and HCV, only 52 cases have been confirmed. A total of 8,819 people living with HIV are registered at the centre.

It has been 18 years since MSF began providing medical assistance in Ukraine, beginning in 1999 when the organisation worked in Mykolaiv, Odessa and Simferopol providing treatment for HIV/AIDS, as well as prevention of mother-to-child transmission of the disease. Now MSF is tackling one of the highest causes of death for this population – the hepatitis C virus co-infection.

In April 2017, MSF signed a Memorandum of Cooperation with the Ministry of Health in Ukraine, to improve hepatitis C treatment and reduce the morbidity and mortality of the virus among a cohort of 1,000 patients, including people living with HIV and hepatitis C, people who have injected drugs and have hepatitis C and around 100 healthcare workers infected with the virus. In May 2017, MSF signed a Memorandum of Cooperation with Mykolaiv Regional State Administration.

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Argentina: Sofosbuvir patent rejected http://www.eatg.org/news/argentina-sofosbuvir-patent-rejected/ Mon, 04 Dec 2017 20:35:24 +0000 http://www.eatg.org/?post_type=news&p=6939 Hepatitis C: In Argentina INPI rejected a key patent on sofosbuvir

Argentina has made an important step forward to protect local production of generics of an essential medicine to treat Hepatitis C. This brings significant advantages for Public Programs which procure the medicines.

Buenos Aires, December 4, 2017. In Argentina, the INPI (National Institute of Industrial Property) rejected GILEAD PHARMASSET LLC patent application on Sofosbuvir prodrug, an essential medicine to treat HepC.

The resolution PN 066898 of INPI that rejects the patent, is based on the same arguments filed by FGEP in the oppositions. In May, 2015, FGEP filed an opposition in which we highlighted Gilead does not comply with the legal requirements of Argentine patent Law. The article 4 requires novelty, inventive step and industrial application. In addition, the Law in articles 12 and 20 requires the invention must be described in the application in a sufficiently clear and complete manner. All requirements that were not met by Gilead application.

GEP and other CSOs stated and proved Gilead intended to claim a patent over an active ingredient of an already known product, that according to the regulation it is not patentable. Sofosbuvir was developed based on knowledge already known and the scientific techniques used to develop Sofosbuvir are routine for chemical-pharmaceutical practices. These arguments were used in the INPI resolution to reject  the patent seek by Gilead.

 In Argentina there are three generic local versions that obtained registration from ANMAT, the Regulatory Authority. “These generics guarantee price competition in the tenders of the Ministry of Health and they should be protected”, highlighted Lorena Di Giano, Executive Director of FGEP, who is working in the filling as a Lawyer and Agent of Industrial Property.

The exorbitant price of the medicines for HepC is the main barrier for access, many people are in waiting lists to get the treatment. Some of them may not make it. This is unacceptable”, stated Pablo García, President of FGEP.

 The file of the application on Sofosbuvir prodrug was also opposed by local producers who  in spite of this application and others, invested to develop the product and obtained ANMAT registration.

 Today there is a public tender opened by the Ministry of Health in which some of the local producers have offered significantly lower prices than Gilead. The rejection of this patent is a step forward to protect local production and procurement of generics” added Lorena Di Giano.

 In the first purchase of DAAs made by the Ministry of Health in March 2015, the Argentinian company Richmond offered a 4 times lower price than Gilead who intended to get several patents on Sofosbuvir, most of them are pending.

We hope the pending patents over Sofosbuvir are rejected by INPI soon. The unsolved patent applications create monopolies and insecurity in the market to produce generics”, said José María Di Bello, Secretary of FGEP.

Gilead intends to illegally obtain the rights on Sofosbuvir through patent applications that do not meet the requirements of the law. The treatment for Sofosbuvir combined with other DAAs  has a proven effectiveness of 95% in patients with HepC.

 In Argentina, it is estimated that there are 400.000 people living with HepC, many of them are in an advanced stage of the illness and do not have access to the treatment due to the high prices. The existence of generics has a direct impact on the Ministry of Health Budget and allows more people to obtain the cure.

FGEP Campaign to promote Universal Access to Hepatitis C treatment.

https://youtu.be/CP5p75BAWiE

https://youtu.be/G5OagLqY3dc

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New guidelines target HBV as public health priority http://www.eatg.org/news/new-guidelines-target-hbv-as-public-health-priority/ Mon, 04 Dec 2017 20:15:07 +0000 http://www.eatg.org/?post_type=news&p=6942 Screening, vaccinating and providing health-care services and resources to individuals infected with the hepatitis B virus (HBV) are US public health priorities.

To make that message clear, the American College of Physicians (ACP) and US Centers for Disease Control and Prevention (CDC) have released new best practice guidelines to address the liver-attacking virus.

About 847,000 people in the US are living with chronic HBV, with 14,000 deaths in the country attributable to the virus each year, researchers from the ACP and CDC reported in a recent study.

“Prior recommendations have not accomplished the critical goals of screening high risk populations, vaccinating those who are at risk, and referring for care those who are already infected,’’ Jack Ende, MD, MACP, President, ACP, told MD Magazine. “The current guidelines are straightforward and should be of great value for clinicians, health-care workers and patients.’’

The authors examined literature on clinical guidelines, systematic reviews, randomized trials and intervention studies involving HBV vaccination, screening and linkage to care published between January 2005 and June 2017.

They concluded that vaccination is the most effective way to prevent HBV infection and its complications.

All adults, including pregnant women, who are at risk for infection because of sexual, percutaneous or mucosal exposure should be vaccinated, the guidelines recommend. In addition, health care and public safety workers at risk for blood exposure; adults with chronic liver disease, end-stage renal disease, or human immunodeficiency virus (HIV) infection; travelers to HBV-endemic regions; and adults seeking protection from HBV infection should also get the vaccine.

“Vaccination confers 90% protection in adults younger than 40 who receive the complete vaccination series. Immunity lasts at least 30 years,” Ende said. “This is extraordinary. Now we need to do all we can to implement these guidelines.”

Screening for HBV in high-risk persons is crucial to stem the virus, the guidelines advise. Pregnant women and infants born to HBV-infected mothers are among those who require screening.

“Many of the risk factors for hepatitis B also portend non-adherence,’’ Ende said, citing injection drug users, prison inmates and people at risk of sexual exposure. “But with public health efforts, these important populations can be reached, and proper screening, vaccination and care provided.”

Other high-risk groups where screening is recommended include people born in countries with 2% or higher HBV prevalence; those living with HIV or hepatitis C (HCV); persons requiring immunosuppressive therapy; those with end-stage renal disease; blood and tissue donors; and people with elevated alanine aminotransferase levels, the researchers wrote.

Screening is important because two-thirds of people chronically infected with HBV are unaware of their status, a situation that contributes to ongoing transmission, the authors noted.

The third step in the new guidelines advises clinicians to provide post-test counseling and HBV-directed care — or to refer all patients identified with HBV to professionals who can help them.

Between 15% and 40% of persons with chronic HBV infection develop cirrhosis, hepatocellular carcinoma, or liver failure, and 25% die prematurely of these complications, the authors wrote.

“We need all the oars in the water,’’ said ACP’s Ende, whose organization is the largest medical specialty group in the US with members in more than 145 countries.

Efforts to implement the guidelines begin with primary care practices, correctional facilities and public health sites that administer care, he said.

“But given that patients with liver disease and renal disease, as well as pregnant women, are candidates for screening and vaccinations, specialists need to be involved as well,’’ Ende said.

The study, “Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention,” was published online in Annals of Internal Medicine last month.

By Gail Connor Roche

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Hepatitis publications http://www.eatg.org/news/hepatitis-publications/ Mon, 04 Dec 2017 19:19:22 +0000 http://www.eatg.org/?post_type=news&p=6948
  • Healio: HCC rates after interferon-free HCV treatment linked to baseline risk factors
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    Sofosbuvir/ledipasvir for 8 weeks cures acute HCV in people with HIV http://www.eatg.org/news/sofosbuvirledipasvir-for-8-weeks-cures-acute-hcv-in-people-with-hiv/ Tue, 28 Nov 2017 21:21:50 +0000 http://www.eatg.org/?post_type=news&p=6863

    An 8-week course of sofosbuvir/ledipasvir (Harvoni) led to a sustained response in all people with HIV and genotype 1 or 4 hepatitis C virus (HCV) in the SWIFT-C study, according to a report at the AASLD Liver Meeting last month in Washington, DC.

    The advent of direct-acting antivirals (DAAs) has made treatment for chronic hepatitis C shorter, better tolerated and much more effective, even for people – such as those with HIV/HCV co-infection – who were considered difficult to treat with interferon-based therapy. The recommended duration of sofosbuvir/ledipasvir for genotype 1 or 4 chronic HCV is 12 weeks, though some easy-to-treat people do well with 8 weeks.

    Acute hepatitis C, meaning the first 6 months after infection, is generally easier to treat than chronic infection. Studies to date have shown that an 8-week course of sofosbuvir/ledipasvir is adequate for treatment of genotype 1 HCV during acute infection in HIV-negative people, and one study found that even a 6-week course works well for this group. But stopping at 6 weeks led to an unexpectedly high relapse rate for people with HIV/HCV co-infection, and some experts have recommended treating this group for a full 12 weeks.

    Susanna Naggie of Duke University Medical Center and colleagues conducted the AIDS Clinical Trials Group SWIFT-C trial to evaluate the efficacy of 8 weeks of sofosbuvir/ledipasvir for people with HIV who had acute HCV co-infection.

    The study enrolled 27 HIV-positive participants with acute HCV infection at multiple sites in the US. Acute HCV was defined as a newly positive HCV RNA (viral load) or antibody test within 6 months after a prior negative test, or recent liver enzyme elevation and detectable HCV RNA. Participants waited until 12 weeks after infection to see if spontaneous or natural clearance would occur without treatment, which happens around 25% of the time.

    All study participants were men, the median age was 46 years, two-thirds were white and a third were Hispanic. More than 80% said they had never injected drugs and it was assumed they may have acquired HCV through sexual transmission. All had HCV genotype 1, except one person with genotype 4. About one in five had a high HCV RNA viral load (over 6 million IU/ml) at baseline.

    All participants were on antiretroviral therapy (ART) with undetectable HIV viral load. They had well-preserved immune function, with a median CD4 count of 561 cells/mm3. They were on various ART regimens, with about half using an HIV integrase inhibitor. Nine people were taking a regimen that included tenofovir disoproxil fumarate (DF) (Viread) and either ritonavir or cobicistat as a booster. Sofosbuvir/ledipasvir may increase tenofovir levels when co-administered with a ritonavir-boosted protease inhibitor, with elvitegravir boosted by cobicistat or with efavirenz or rilpivirine. Unusually high levels of tenofovir DF may cause kidney problems and bone loss in some people.

    Everyone in this single-arm study received sofosbuvir/ledipasvir for 8 weeks; there was no control arm. The primary study endpoint was sustained virological response, or continued undetectable HCV RNA at 12 weeks after the end of treatment (SVR12).

    All participants completed treatment and achieved SVR12 – a cure rate of 100%. This compares favourably to a historical cure rate of 60% using pegylated interferon plus ribavirin for 24 to 48 weeks.

    Sofosbuvir/ledipasvir was generally safe and well tolerated. There was only one serious adverse event, which was not considered related to treatment. A third of participants experienced moderate or worse adverse events. Two people who used tenofovir DF in a boosted regimen met the criteria for kidney toxicity.

    Based on these findings, the researchers concluded, “These data support an 8-week duration of [sofosbuvir/ledipasvir] in the treatment of acute HCV infection in HIV-infected persons.”

    In response to a question from Jürgen Rockstroh, who conducted the study that showed a high relapse rate with only 6 weeks of sofosbuvir/ledipasvir for people with co-infection, Naggie acknowledged that people with higher viral load took longer to reach an undetectable level, and doctors might consider 12 weeks of treatment for people with very high baseline HCV RNA.

    Given the difficult side-effects and comparatively low cure rate of interferon-based therapy, treatment guidelines used to advise waiting a few months after HCV infection to see if spontaneous clearance would occur without treatment. But given the good tolerability and excellent response rate with DAAs, a growing number of experts recommend prompt treatment of acute infection, which not only relieves symptoms of acute infection and prevents liver damage, but also halts HCV transmission at a time when viral load may be high.

    People with acute infection are potential HCV transmitters, and if you let patients leave to wait for possible spontaneous clearance, they are less likely to come back, Naggie said. “Once you have them in your clinic, you should treat them,” she advised.

    By Liz Highleyman

    Reference

    Naggie S et al. Sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C). The Liver Meeting, abstract 196, 2017.

    View the abstract.

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    Low skeletal muscle mass improves after successful HCV treatment http://www.eatg.org/news/low-skeletal-muscle-mass-improves-after-successful-hcv-treatment/ Thu, 23 Nov 2017 20:18:02 +0000 http://www.eatg.org/?post_type=news&p=6834 Skeletal muscle mass increased significantly among patients with hepatitis C and low skeletal muscle mass after achieving sustained virologic response with direct-acting antiviral therapy, according to recently published data.

    “Changes in body composition, such as the accumulation of visceral fat or thinness, are known to effect patients with chronic HCV including liver cirrhosis,” Ryosuke Sugimoto, MD, PhD, from the Mie University Graduate School of Medicine, Japan, and colleagues wrote. “An understanding of the various measurements of body composition, such as the amount of body fat and skeletal muscle mass, is required to properly examine liver disease patients.”

    The researchers enrolled 30 patients who achieved sustained virologic response after treatment with direct-acting antiviral therapy and had available body composition measurements.

    At the start of DAA therapy, 14 patients had chronic HCV, 16 had compensated cirrhosis, three had visceral obesity and nine had low skeletal muscle mass. Those with low skeletal muscle mass (LSM) had significantly lower BMI (20.3 vs. 22.9 kg/m2; P < .01) compared with the other patients.

    The patients had received nutritional counseling to address chronic liver disease for more than 6 months prior to DAA therapy. Researchers advised patients to engage in 20 minutes of aerobic exercise two to three times per week, though they did not confirm adherence.

    Among those with LSM, serum albumin levels increased significantly at 48 weeks after DAA therapy (P < .05) and skeletal muscle mass index (SMI) increased at both 24 and 48 weeks (P < .05). Two patients exceeded the SMI reference value, which placed them outside the clinical range of LSM.

    At 48 weeks post-DAA therapy, change in SMI correlated significantly with change in weight (r = 0.403; P < .05) among those with LSM. The researchers found that an increase in SMI correlated with an increase in body weight (regression coefficient beta = 0.172; 95% CI, 0.14-0.204) and a decrease in visceral fat area (regression coefficient beta = –0.044; 95% CI, –0.052 to –0.035).

    “The increase in skeletal muscle mass was only observed in HCV patients who exhibited LSM before DAA therapy. Notably, skeletal muscle mass in two patients (14%) completely returned to normal levels, thus overcoming LSM, indicating the possibility that more patients may overcome LSM given a longer observation period.”

    Sugimoto R, et al. Hepatol Res. 2017;doi:10.1111/hepr.12999.

    By Talitha Bennett

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    Clinical guideline on HBV released by ACP, CDC http://www.eatg.org/news/clinical-guideline-on-hbv-released-by-acp-cdc/ Wed, 22 Nov 2017 22:40:21 +0000 http://www.eatg.org/?post_type=news&p=6829 A new clinical guideline on hepatitis B virus (HBV) urges physicians to vaccinate all unvaccinated adults who are at risk for infection, including pregnant women, and routinely screen at-risk adults.

    The American College of Physicians (ACP) and the Centers for Disease Control and Prevention (CDC) published the clinical guideline online on November 20 in Annals of Internal Medicine. The authors also direct clinicians to refer all HBV-infected individuals for appropriate care and counseling.

    “Although these topics have been addressed previously in clinical guidelines from the CDC, the U.S. Preventive Services Task Force (USPSTF), the American Association for the Study of Liver Diseases (AASLD), and the Advisory Committee on Immunization Practices, their recommendations vary and implementation has been suboptimal,” Winston E. Abara, MD, PhD, from the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, and colleagues report. “Most persons who are at risk for, are susceptible to, or have HBV infection are not screened, vaccinated, or linked to care,” they write. “Recent studies have suggested additional at-risk groups that should receive HBV screening, treatment, or vaccination that were not in previously published clinical guidelines.”

    “The majority of people who are at risk for hepatitis B are not being appropriately screened or if they do have the disease, they are not being referred and linked to care. This is a cost-effective measure and the uptake is way too low,” Jack Ende, MD, president of the ACP, said in a video statement accompanying the report. “Chronic hepatitis B can lead to cirrhosis, liver failure, or primary liver cancer. About 25% of infected patients will die premature[ly] from one of these complications. The HBV vaccination is the most effective way to prevent this illness and therefore its complications,” he said.

    The authors reviewed the literature on evidence for HBV vaccination, screening, and linkage to care and integrated new evidence with consensus across guidelines, using a high-value care framework developed by the ACP.

    With respect to vaccination, the evidence supports universal vaccination for adults seeking protection from HBV infection and those deemed to be at increased risk for infection as a result of the following:

    • Sexual exposure;
    • Percutaneous or mucosal exposure to blood;
    • Chronic liver disease;
    • End-stage renal disease;
    • HIV infection;
    • Infection risk behaviors during pregnancy; or
    • International travel to regions with high or intermediate levels of endemic HBV infection.

    Some of these individuals — particularly those who are immunocompromised or who have end-stage renal disease — may warrant higher vaccine dosages than dosages achieved through the typical three- or four-dose HBV vaccine series to ensure optimal protection, the authors write. Further, they note, “[t]hese persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg [hepatitis B surface antigen] level < 10 mIU/mL) should be revaccinated.”

    Adverse effects from HPV vaccine are rare and mild, the authors stress. “[T]he most common are soreness at the injection site (3% to 29%) and mild fever (1% to 6%),” they write, noting that postvaccination anaphylaxis is rare, occurring once per 1.1 million doses.

    Screening for HBV, via seromarkers for hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen should be conducted in high-risk populations, including

    • Individuals born in countries with 2% or higher HBV prevalence;
    • Men who have sex with men;
    • Intravenous drug users;
    • HIV-positive individuals;
    • Individuals with household and sexual contacts to HBV-infected persons;
    • Individuals requiring immunosuppressive therapy;
    • Individuals with end-stage renal disease;
    • Blood and tissue donors;
    • Individuals infected with hepatitis C virus;
    • Persons with elevated alanine aminotransferase levels (≥19 IU/L for women and ≥30 IU/L for men);
    • Incarcerated individuals;
    • Pregnant women; and
    • Infants born to HBV-infected mothers.

    Although current guidelines from the CDC, the USPSTF, and the AASLD recommend screening for persons born in regions with intermediate-to-high prevalence of HBV infection or with other known HBV-related risks, as well as prevaccination testing for healthcare personnel at increased risk for HBV infection and those who perform exposure-prone procedures, “screening in these groups is suboptimal,” the authors write.

    The advice also extends to linking HBV-infected individuals to care and counseling as necessary. “Although not all patients with chronic HBV infection require treatment, they all should be routinely evaluated for hepatocellular carcinoma and treatment eligibility through history and physical examination,” the authors state, pointing to evidence indicating that such linkages can significantly reduce HBV-associated morbidity and mortality.

    “However, most persons with chronic HBV infection are not linked to care because they are unaware of their infection or are not referred despite their diagnosis,” the authors report. This means that many of the 20% and 40% of individuals with chronic HBV infection who require treatment are not getting it, nor are their liver aminotransferase and HBV DNA levels being monitored, which is recommended for all HBV-infected individuals, they add.

    In addition, “[o]nly 10% to 15% of eligible persons receive antiviral therapy, demonstrating that many who could benefit from therapy do not receive it,” the authors explain. “Linkage to care ensures that patients with chronic HBV infection receive treatment when they become eligible (elevated HBV DNA and liver aminotransferase levels), hepatocellular carcinoma surveillance, behavioral risk reduction counseling, and vaccination of susceptible sexual and household contacts,” they state.

    For these reasons, all patients identified as HBsAg-positive should be referred for post-test counseling and HBV-directed care.

    Multiple patient-, clinician- and system-level barriers prevent optimal uptake of HBV vaccination recommendations, the authors note. Examples include lack of knowledge or information about HBV infection and the benefits of the vaccine in the general public, as well as limited health literacy in certain populations. At the clinician level, lack of awareness of clinical care guidelines or population-specific risks for HBV infection, inadequate screening, and vaccine storage challenges are cited as obstacles. System-level barriers include inadequate funding and challenges associated with specialty referrals, the authors write.

    Various strategies for overcoming these barriers are offered, including targeted patient and clinician education, universal screening and vaccination protocols, and culturally sensitive outreach and support.

    “The burden and costs associated with chronic HBV infection in the United States are high. Vaccination of susceptible adults is important to prevent infection and reduce ongoing transmission,” the authors state.

    However, the existing, risk-based vaccination strategy may be insufficient for increasing HBV vaccine coverage. “Because the administration schedule typically includes 3 vaccine doses over 6 months, the vaccine series needs to be started and completed before exposure to the risk factor to protect persons at greatest risk,” the authors explain. “Furthermore, the multitude of factors constituting an indication for adult hepatitis B vaccination can create implementation challenges for vaccine providers.” For this reason, “[a]n adult vaccination strategy that is not based on risk may be the next step toward achieving elimination.”

    One author  reports receiving research grants from Gilead Sciences for hepatitis C treatment and seeing patients who receive free hepatitis C medications supplied by Gilead Sciences in the course of his patient care duties. One author is the treasurer of the ACP. One author reports personal fees from Takeda Pharmaceuticals outside the submitted work and is a member of the ACP Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. The remaining authors have disclosed no relevant financial relationships.

    Ann Intern Med. Published online November 20, 2017. Full text

    By Diana Phillips

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    Hepatitis increases mortality rates in HIV patients http://www.eatg.org/news/hepatitis-increases-mortality-rates-in-hiv-patients/ Wed, 22 Nov 2017 20:05:30 +0000 http://www.eatg.org/?post_type=news&p=6828 Patients with HIV coinfected with hepatitis B (HBV) or hepatitis C (HCV) have a significantly greater risk of all-cause or liver-related mortality than those individuals who are HIV mono-infected, a study in AIDS reports.

    Alicia C. Thornton, PhD, of the Research Department of Infection and Population Health at University College London in the UK, and colleagues compared all-cause, liver-related, and AIDS-related mortality rates in mono-infected HIV patients with those rates in co-infected HBV and HCV patients.

    A total of 25,486 HIV patients across 11 UK-based clinics were tested for HBV using a hepatitis B surface antigen (HBsAg) test and HCV using an antibody or HCV RNA test. Causes of death were labeled liver-related, AIDS-related, or neither (all-cause). Liver-related death was defined as death due to decompensated liver disease, hepatocellular carcinoma and liver failure, and metastasized liver cancers.

    Patients were categorized in AIDS-related deaths if AIDS was stated as a cause of death or if the cause of death included AIDS-defining illnesses (using the list of conditions from the CDC).

    Of the patients who were HIV-positive before 2004 (121,814 person-years), 4.2% died during their follow-up time (median follow-up time was 4.6 years per person). Once test results were received, patients were grouped as HIV-monoinfected (89%), HIV/HBV-coinfected (47%), HIV/HCV-coinfected (5.5%), or HIV/HBV/HCV-triple-infected (0.49%).

    The researchers found that all categories of hepatitis-coinfection are significantly associated with an increased risk of all-cause mortality, namely patients with triple infection, who have a 2.29 times greater risk of death than HIV-monoinfected patients. Also significant, HIV/HBV patients (ARR, 1.6) and HIV/HCV patients (ARR, 1.42) have a greater risk of death than HIV-monoinfected patients.

    Liver-caused deaths were much more significant than all-cause rates in all three infection categories. Compared with HIV-monoinfection, the highest risk of mortality was associated with HIV/HBV/HCV (ARR, 15.19), followed by HIV/HBV (ARR, 10.42), and HIV/HCV (ARR, 6.2).

    Hepatitis coinfection was not significantly involved in increasing mortality associated with AIDS, as HBV is not associated with an increase progression of HIV to AIDS. In addition, HIV/HCV-coinfected patients had a significantly lower risk of AIDS-related mortality compared with HIV-monoinfected patients (ARR, 0.4).

    The findings emphasize the needs for primary prevention and effective hepatitis treatments for HIV-positive patients.

    “Directly acting agents for treatment of HCV infection are now available, which have high rates of cure,” stated the authors. “If patients are able to access these treatments the increased risk of mortality from HCV infection may be mitigated.”

    By Rita Aghjayan

    Reference

    Thornton AC, Jose S, Bhagani S, et al. Hepatitis B, hepatitis C, and mortality among HIV-positive individuals. AIDS. 2017;31(18):2525-2532. doi: 10.1097/QAD.0000000000001646

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    Reduced risk of hepatic steatosis in HIV/HCV coinfection with cannabis use http://www.eatg.org/news/reduced-risk-of-hepatic-steatosis-in-hivhcv-coinfection-with-cannabis-use/ Sun, 19 Nov 2017 16:51:12 +0000 http://www.eatg.org/?post_type=news&p=6796 Daily cannabis use was shown to be associated with a reduced risk for liver steatosis among individuals co-infected with HIV and hepatitis C, according to the results of a recent study published in the Journal of Viral Hepatitis.

    In this analysis of patients from a French cohort of people co-infected with HIV and hepatitis C, the association of steatosis and cannabis use was evaluated. Ultrasound examination was used to determine the presence of steatosis, and self-administered questionnaires collected sociobehavioral data, including cannabis use frequency.

    A total of 40.1% (n=336/838) of study participants had liver steatosis. Most participants did not use or only occasionally used cannabis (74.7%), followed by daily use (14.0%) or regular use (11.7%).

    Daily cannabis use was more common among patients who were negative for steatosis compared with those who were positive (16.1% vs 10.7%; P =.08). After adjusting for body mass index, hazardous alcohol consumption, and current or lifetime use of lamivudine or zidovudine, daily cannabis use was correlated with a lower risk for steatosis (adjusted odds ratio [OR] 0.64; 95% CI, 0.42-0.99; P =.046).

    Other factors associated with liver steatosis included high body mass index (adjusted OR 1.93; P =.02), current or lifetime exposure for lamivudine or zidovudine (adjusted OR 1.51; P =.01), and hazardous alcohol consumption (adjusted OR 1.73; P =.03).

    In an interview with Infectious Disease Advisor, Patrizia Carrieri, epidemiologist at the French National Institute of Health and Medical Research INSERM UMR 912, Marseilles, France, and senior author on the study, concluded that, “although we hypothesize that the association between lower steatosis risk and cannabis use may be attributable to the anti-inflammatory properties of cannabis, we must remain cautious about causality.”

    By Jessica Martin

    Reference

    Nordmann S, Vilotitch A, Roux P, et al; ANRS CO13 HEPAVIH Study Group. Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus co-infected patients (ANRS CO13-HEPAVIH) [published online October 6, 2017]. J Viral Hepat. doi: 10.1111/jvh.12797

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    DAAs produce cure rates in HCV/HIV co-infection similar to monoinfection http://www.eatg.org/news/daas-produce-cure-rates-in-hcvhiv-co-infection-similar-to-monoinfection/ Sun, 19 Nov 2017 16:49:24 +0000 http://www.eatg.org/?post_type=news&p=6794 Using direct-acting antiviral therapies demonstrated similarly high rates of sustained virologic response for hepatitis C virus infection in patients with and without HIV infection as compared with rates for HCV mono-infected patients, according to findings published in Hepatology.

    “Because of low [sustained virologic response] rates associated with interferon-based therapies, the accelerated progression of HCV related liver disease, and barriers to receiving treatment, the [FDA] identified those infected with HIV and HCV co-infection as being a specific population with unmet medical needs,” Cameron Sikavi, third-year resident from the department of medicine at Harbor-University of California at Los Angeles Medical Center, and colleagues wrote. “With the advent of [DAA] therapies, HCV treatment has resulted in higher cure rates with short treatment duration in comparison to pegylated-interferon and ribavirin based therapies, in addition to improved safety and tolerability profiles.”

    Prior research has shown that DAA treatment can improve life expectancy and SVR rates. Using clinical databases, researchers performed a systematic review of the treatment for chronic HCV infection in patients infected with HIV to determine whether using DAA agents addresses an unmet medical need in these patients and results in similar SVR rates as HCV mono-infected persons. In their review, the investigators included studies dated between January 2004 and July 2017, searching the keywords “hepatitis C,” “HIV,” “coinfection” and “direct-acting antiviral.”

    Patients with HCV and HIV coinfection treated with interferon-based treatments had substantially lower SVR rates compared with rates seen in HCV mono-infected patients. Mono-infected persons who started taking DAA agents had similar SVR rates as compared with co-infected persons, with SVR greater than 93%. In comparison to interferon-based regimens, DAA medications have been shown to have improved the safety, efficacy and tolerability in both co-infected and mono-infected patients. Sikavi and colleagues also note that physicians should be aware of antiretroviral medications for HIV before starting a patient on HCV treatment, and of comorbidities that may impact SVR.

    “Given the success of DAA therapy, it is imperative that future research be aimed at identifying programs and interventions that reduce the risk of reinfection among this population,” Sikavi and colleagues wrote. “Clinicians must remain vigilant, especially with regard to identifying drug-drug interactions, negative predictors or SVR, and barriers to care. By doing so, the improvements in SVR rates afforded with DAAs can address an unmet medical need among the coinfected population, with significant clinical implications.”

    Sikavi C, et al. Hepatology. 2017doi:10.1002/hep.29642.

    By Savannah Demko

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    FDA approves hepatitis C drugs label updates http://www.eatg.org/news/fda-approves-hepatitis-c-drugs-label-updates/ Sun, 19 Nov 2017 16:47:00 +0000 http://www.eatg.org/?post_type=news&p=6780 FDA recently approved changes to the labels of:

    • Sovaldi (sofosbuvir), Harvoni (ledipasvir and sofosbuvir), Epclusa (sofosbuvir and velpatasvir) and Vosevi (sofosbuvir, velpatasvir, and voxilaprevir). The approved changes are detailed here.
    • VIEKIRA PAK™ (ombitasvir, paritaprevir, and ritonavir tablets, 12.5 mg/75 mg/50 mg; dasabuvir tablets, 250 mg), VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) and TECHNIVIE (ombitasvir, paritaprevir, and ritonavir). The approved changes are detailed here.
    • OLYSIO (simeprevir), DAKLINZA (daclatasvir) and ZEPATIER (grazoprevir/elbasvir). The approved changes are detailed here.
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    Eliminating viral hepatitis: time to match visions with action http://www.eatg.org/news/eliminating-viral-hepatitis-time-to-match-visions-with-action/ Sat, 11 Nov 2017 22:43:28 +0000 http://www.eatg.org/?post_type=news&p=6750 Viral hepatitis caused an estimated 1·4 million deaths in 2015—similar to tuberculosis and more than either HIV or malaria, yet historically these diseases have received insufficient attention from donors and policy makers. In May, 2016, the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis, 2016–20, which aims to eliminate viral hepatitis as a major public health threat by 2030. The strategy set global targets to reduce new viral hepatitis infections by 90% and to reduce deaths due to viral hepatitis by 65%, focusing mainly on hepatitis B virus (HBV) and hepatitis C virus (HCV), which are responsible for most of the global burden. Last week, politicians, policy makers, researchers, and members of civil society met in São Paulo, Brazil, at the World Hepatitis Summit to take stock, with new data indicating that only a handful of countries are set to meet the 2030 targets.

    Practices associated with increased risks of contracting HBV and HCV have contributed to stigma and discrimination against patients, especially prisoners and people who inject drugs. Prevention of both diseases involves reducing the risks of exposure to the viruses, and, for hepatitis B, vaccination. Acute HBV and HCV infection tend to be asymptomatic; however, chronic infections can lead to cirrhosis and hepatocellular carcinoma. Antiviral treatment for hepatitis B is not curative, but can slow disease progression and improve survival, whereas direct-acting antiviral (DAA) therapy for hepatitis C can cure around 95% of cases.

    New data from WHO, released at the summit, showed the number of people who were newly treated for hepatitis C increased from 1·1 million in 2015 to 1·76 million in 2016. Likewise, 2·8 million people began treatment for hepatitis B in 2016, up from 1·7 million in 2015. Despite these improvements, data from the Polaris Observatory indicated that although 82 countries now have viral hepatitis plans, only nine (Australia, Brazil, Egypt, Georgia, Germany, Iceland, Japan, the Netherlands, and Qatar) are on track to reach their 2030 elimination goals for hepatitis C. Globally, a major challenge is diagnosis, with many countries “running out” of patients with hepatitis C to treat, according to the World Hepatitis Alliance. Indeed, new Polaris data indicate that just 20% of people with HCV have been diagnosed, ranging from around 44% in high-income countries to 9% in low-income countries.

    The price of DAAs, especially in high-income countries, is a barrier to providing effective treatment, with the list price of a 12-week course of sofosbuvir and daclatasvir ranging from US$78 in India to $77 000 in the UK and around $96 000 in the USA. Like many high-income countries, Australia initially restricted access to DAAs. But in March, 2016, following the implementation of a risk-sharing agreement with pharmaceutical companies, Australia initiated universal access. On a background of high diagnosis rates, this led to the treatment of over 30 000 patients in 2016. Challenges for the USA include the opioid crisis, which has caused some states to see steep increases in new HCV infections through injection drug use. Stretched prison budgets mean that although an estimated one in six prisoners has hepatitis C, few are treated.

    Children represent a particular challenge. The Polaris Observatory estimates that 52 million children were living with viral hepatitis in 2016—4 million with HCV and 48 million with HBV. Whereas new HBV infections are declining in children owing to vaccine use, new HCV infections are on the rise. Mother-to-child transmission was the main source of paediatric HCV infection, pointing to the need for comprehensive prevention programmes for women of childbearing age. Worryingly, treatment options are limited, with DAAs not recommended for pregnant women or children younger than 12 years. Writing in a recent Series paper for The Lancet Gastroenterology & Hepatology, Wendy Spearman and colleagues argue that prevention of mother-to-child transmission through screening and treatment is a key priority for HBV elimination in sub-Saharan Africa.

    Several innovations could accelerate progress towards 2030 targets, including improved point-of-care diagnostics, establishing better treatment options for young children and pregnant women with hepatitis C, developing a functional cure for hepatitis B, improving access to generic DAAs, raising awareness and combating stigma, and developing sustainable financing models as part of progress towards universal health coverage. Yet, fundamentally, the tools needed to move towards elimination targets already exist—an effective vaccine for hepatitis B and a curative treatment for hepatitis C. What is needed now more than anything else is the political will to scale up prevention, diagnosis, and treatment programmes.

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    Dynavax announces FDA approval of HEPLISAV-B(TM) for prevention of hepatitis B in adults http://www.eatg.org/news/dynavax-announces-fda-approval-of-heplisav-btm-for-prevention-of-hepatitis-b-in-adults/ Sat, 11 Nov 2017 22:07:14 +0000 http://www.eatg.org/?post_type=news&p=6752 First and only two-dose vaccine in United States for prevention of hepatitis B in adults
    First new hepatitis B vaccine in United States in more than 25 years

    BERKELEY, CA — 11/09/17 — Dynavax Technologies Corporation (NASDAQ: DVAX) today announced that the U.S. Food and Drug Administration (FDA) has approved HEPLISAV-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)] for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. HEPLISAV-B is the first new hepatitis B vaccine in the United States in more than 25 years and the only two-dose hepatitis B vaccine for adults.

    Hepatitis B is an extremely infectious and potentially deadly virus affecting a wide range of adults in the United States. There is no cure for hepatitis B, and infections are on the rise. In 2015, new cases of acute hepatitis B increased by more than 20 percent nationally.(i) Hepatitis B can be prevented through effective vaccination. Current hepatitis B vaccines require three shots over a six-month period, however, almost half of adults fail to complete the series within one year.(ii)

    “Prevention of hepatitis B in adults through vaccination is more important than ever given the increase in the rate of infections,” said William Schaffner, M.D., professor of Preventive Medicine, Vanderbilt University Medical Center. “Too many at-risk adults remain unprotected against this virus. A two-dose schedule with higher rates of protection, along with other strategies, may help us move closer to the goal of eliminating hepatitis B as a public health problem in the United States.”

    The approval of HEPLISAV-B was based on data from three Phase 3 non-inferiority trials of nearly 10,000 adult participants who received HEPLISAV-B. The pivotal studies compared HEPLISAV-B administered in two doses over one month to Engerix-B administered in three doses over a six-month schedule. Results from the largest Phase 3 trial, which included 6,665 participants, showed that HEPLISAV-B demonstrated a statistically significantly higher rate of protection of 95% compared with 81% for Engerix-B. In a subgroup analysis of 961 participants with Type 2 diabetes, HEPLISAV-B demonstrated a statistically significantly higher rate of protection of 90% compared to 65% for Engerix-B. Across the three clinical trials, the most common local reaction was injection site pain (23% to 39%). The most common systemic reactions were fatigue (11% to 17%) and headache (8% to 17%).

    “HEPLISAV-B is the first FDA-approved product for Dynavax and demonstrates our ability to develop innovative products and progress them from discovery to commercialization,” said Eddie Gray, chief executive officer of Dynavax. “We would like to thank the many study participants and clinical trial investigators who contributed to the development of HEPLISAV-B. We expect that it will become an essential tool in the public health community’s fight to prevent hepatitis B, and we look forward to making HEPLISAV-B available to clinicians and their adult patients.”

    Dynavax expects to commercially launch HEPLISAV-B in the United States in the first quarter of 2018. In preparation for launch, Dynavax has been building commercial infrastructure and optimizing manufacturing processes to meet anticipated demand.

    About Hepatitis B

    Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer and death. The hepatitis B virus is 50 to 100 times more infectious than HIV,(iii) and transmission is on the rise. There is no cure for hepatitis B, but effective vaccination can prevent the disease. In adults, hepatitis B is spread through contact with infected blood and through unprotected sex with an infected person. The CDC recommends vaccination for those at high risk for infection due to their jobs, lifestyle, living situations and travel to certain areas.(iv) Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults age 19 to 59 with diabetes as soon as possible after their diagnosis, and for people age 60 and older with diabetes at their physician’s discretion.(v) Approximately 20 million U.S. adults have diabetes, and 1.5 million new cases of diabetes are diagnosed each year.(vi)

    About HEPLISAV-B

    HEPLISAV-B is an adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary Toll-like Receptor (TLR) 9 agonist to enhance the immune response. Dynavax has worldwide commercial rights to HEPLISAV-B.

    Indication and Use
    HEPLISAV-B is indicated for active immunization against infection caused by all known subtypes of hepatitis B virus. HEPLISAV-B is approved for use in adults 18 years of age and older.

    Important Safety Information (ISI)
    Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast.

    Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B.

    Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B.

    Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

    The most common patient reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%) and headache (8% to 17%).

    For full Prescribing Information for HEPLISAV-B, click here.

    About Dynavax

    Dynavax is a commercial-stage biopharmaceutical company focused on leveraging the power of the body’s innate and adaptive immune responses through toll-like receptor (TLR) stimulation. Dynavax discovers and develops novel vaccines and immuno-oncology therapeutics. The Company’s first commercial product, HEPLISAV-B, a hepatitis B vaccine for adults, is approved in the United States. Dynavax’s lead immunotherapy product, SD-101, is an investigational cancer immunotherapeutic currently being evaluated in Phase 1/2 studies and its second cancer immunotherapeutic, DV281, is in Phase 1 development. For more information, visit www.dynavax.com.

    Forward-Looking Statements

    This press release contains forward-looking statements, including statements regarding the commercial launch and manufacturing of HEPLISAV-B. These statements are subject to a number of risks and uncertainties that could cause actual results to differ materially, including whether the company will be able to build the commercial infrastructure required to launch HEPLISAV-B; whether we will launch HEPLISAV-B in the first quarter of 2018; whether we will be able to ramp up manufacturing activities to meet demand for HEPLISAV-B; whether the CDC’s Advisory Committee on Immunization Practices (ACIP) will add HEPLISAV-B to its adult vaccination schedule during its February 2018 meeting, or at all; whether potential claims against us, including those based on patent rights of others, will result in an injunction against sales or otherwise impact commercialization and sales; and the results of clinical studies of Dynavax’s product candidates, such as SD-101, and the impact of those results on the initiation or continuation of subsequent studies for those product candidates, and issues arising in the regulatory process; and other risks detailed in the “Risk Factors” section of our most recent current periodic report filed with the SEC. These statements represent our estimates and assumptions only as of the date of this press release. We do not undertake any obligation to update publicly any such forward-looking statements, even if new information becomes available. Information on Dynavax’s website at www.dynavax.com is not incorporated by reference in our current periodic reports with the SEC.

    (i) CDC. https://www.cdc.gov/hepatitis/statistics/2015surveillance/index.htm#tabs-5-8. Fig 3.2

    (ii) Nelson J, et al. Compliance with multiple-dose vaccine schedules among older children, adolescents and adults: results from a Vaccine Safety Datalink Study. American Journal of Public Health. 2009;99:S2.

    (iii) CDC. https://www.cdc.gov/hepatitis/hbv/bfaq.htm.

    (iv) CDC. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm.

    (v) CDC. https://www.cdc.gov/diabetes/pubs/pdf/hepb_vaccination.pdf.

    (vi) CDC. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf.

    Image Available: http://www.marketwire.com/library/MwGo/2017/11/8/11G147587/Images/hepb-fab984ddaa4ebb00a1a5ba03aca78e61.jpg
    Image Available: http://www.marketwire.com/library/MwGo/2017/11/8/11G147587/Images/Dynavax_Building-54e93584329dbdfcbf1f312d8737f6cd.jpg

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    FDA guidance for industry on DAA development for hepatitis C http://www.eatg.org/news/fda-guidance-for-industry-on-daa-development-for-hepatitis-c/ Thu, 09 Nov 2017 20:20:12 +0000 http://www.eatg.org/?post_type=news&p=6742 FDA published a final guidance on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. The guidance can be found at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm225333.pdf

    This guidance assists sponsors in the clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) from the pre-investigational new drug application stage through the new drug application and post-marketing stages.  This guidance finalizes the draft guidance of the same name issued in May 2016.  Major changes from the draft include the following:

    • Modification of several sections to focus on interferon-free DAA regimens.
    • Additional clarification on trial designs for combinations of investigational DAAs with or without ribavirin.
    • Additional clarification on the recommended trial population to include patients with clinical or laboratory evidence of CHC disease.
    • Additional details on DAA drug development in patients with decompensated cirrhosis.
    • Additional clarification on efficacy endpoints.
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    Promising new drug for hepatitis B tested http://www.eatg.org/news/promising-new-drug-for-hepatitis-b-tested/ Wed, 08 Nov 2017 21:02:20 +0000 http://www.eatg.org/?post_type=news&p=6718 Promising new drug for hepatitis B tested at Texas Biomedical Research Institute

    San Antonio, Texas (November 7, 2017) – Research at the Southwest National Primate Research Center (SNPRC) on the campus of Texas Biomedical Research Institute helped advance a new treatment now in human trials for chronic hepatitis B virus (HBV) infection. Testing at SNPRC provided proof this novel therapeutic approach and drug delivery mechanism would be safe and effective, as recently published in the international journal Science Translational Medicine.

    The World Health Organization characterizes hepatitis B as a major global health problem. An estimated 250 to 400 million people are chronically infected with the virus. More than 800,000 people a year die from complications of cirrhosis of the liver and liver cancer. A vaccine that is 95% effective in preventing hepatitis B infections has been available since 1982, but there is currently no cure for the millions already chronically infected.

    The novel therapy by Arrowhead Pharmaceuticals uses a mechanism called RNA interference to reduce the surface antigens created by chronic HBV infections. Surface antigens (called HBsAg) are small molecules involved in virus entry into liver cells. In chronic infection, they may prevent the immune response from clearing the virus. For example, a high level of HBsAg can lead to a greater risk of long-term, chronic infection with hepatitis B and life-threatening complications like cirrhosis and liver cancer. In this setting, reducing HBsAg by RNA interference will have beneficial effects.

    Much of the groundbreaking work lies in the technology Arrowhead developed for delivering this small interfering RNA precisely to the liver. Experiments involving chimpanzees at the SNPRC from 2013-2015 provided the proof that this technology works and is safe for humans, laying the groundwork for the patient clinical trials that have followed. Trials of targeted HBV intervention in non-human primates showed the experimental drug was safe and effective enough to be tested in people.

    The Director of the SNPRC, Robert Lanford, Ph.D., explained this novel treatment — in combination with conventional HBV therapy — could empower the immune system to kill the HBV-infected cells and potentially cure people of the disease.

    “We now have a drug that can knock down hepatitis B surface antigen and determine whether or not we can actually cure people with that,” Dr. Lanford said.

    The drug is delivered by subcutaneous (under the skin) injection. Scientists designed a molecule that delivers the medicine directly to the liver where it binds to a receptor. Then, another molecule that’s derived from bee venom, helps break through membranes in the liver cells to deliver the medicine directly into the cytoplasm of the cells where it takes effect. The siRNA interferes with the expression of the HBV messenger RNA that produces the surface antigen.

    “The idea is if you could knock the levels of surface antigens down far enough, the immune system would kick back in,” Dr. Lanford said. “This technology is pretty specific for the liver right now, but there are a lot of problems in the liver that you can fix with this besides hepatitis B.”

    This kind of targeted therapy may someday be used to develop drugs for other chronic liver conditions like a genetic disorder called Alpha-1 antitrypsin deficiency, caused by mutated inherited genes, which can cause cancer.

    The paper outlining the phase two clinical trials in people and the previous studies involving non-human primates was published in the September 27, 2017 edition of the journal Science Translational Medicine, an interdisciplinary medical journal established by the American Association for the Advancement of Science.

    Although the SNPRC no longer uses chimpanzees for biomedical research, studies conducted with these non-human primates over decades continue to yield significant scientific information that will advance human health.

    ###

    Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world’s leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. The Institute is home to the Southwest National Primate Research Center (SNPRC) and provides broad services in primate research. SNPRC contributes to a national network of National Primate Research Centers (NPRCs) with specialized technologies, capabilities and primate resources, many of which are unique to the SNPRC. The Center also serves investigators around the globe with research and technical procedures for collaborative projects. For more information on Texas Biomed, go to www.TxBiomed.org or for more information on SNPRC, visit www.SNPRC.org.

    Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com.

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    ACHIEVE Coalition sends open letter to Romanian MoH http://www.eatg.org/news/achieve-coalition-sends-open-letter-to-romanian-moh/ Tue, 07 Nov 2017 22:59:07 +0000 http://www.eatg.org/?post_type=news&p=6699 The ACHIEVE Coalition sent this open letter to the Minister of Health of Romania today. The letter, co-signed by EATG as a member of ACHIEVE, calls the Romanian government to prioritise viral hepatitis in health policies of the European Union when acting as the President of the EU Council in 2019.

    “Your support would be invaluable in helping the European Union, its Member States and countries across Europe to deliver on their commitments to eliminate hepatitis B and C by 2030 as set out in the WHO Global Strategy and WHO Europe Action Plan. Action in this area will also complement implementation of the EU’s UN Sustainable Development Goals’ (SDG) commitments to end the epidemics of AIDS, tuberculosis and combat hepatitis” – states the open letter.

    Read the full letter here: 171107 ACHIEVE letter Minister Bodog on priorities for Romanian Council Presidency

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    Worldwide 52 million children living with viral hepatitis http://www.eatg.org/news/worldwide-52-million-children-living-with-viral-hepatitis/ Tue, 07 Nov 2017 22:55:59 +0000 http://www.eatg.org/?post_type=news&p=6706 New data presented at this year’s World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) show that 52 million children are living with viral hepatitis worldwide, compared to 2.1 million children living with HIV/AIDS.

    An estimated 325 million people were living with viral hepatitis worldwide in 2016. Of these, 4 million were children living with hepatitis C (under 19 years) and 48 million (under 18 years) were children living with hepatitis B. Both viruses can lead to liver disease, liver cancer and deaths.

    “Children are suffering a huge burden of viral hepatitis worldwide, and the public health implications of this are enormous,” says Raquel Peck, CEO of World Hepatitis Alliance. “Most infected infants and children are not diagnosed, prioritised or treated effectively.”

    According to new analysis on hepatitis C in children, from Manal El-Sayed, Professor of Pediatrics at Ain Shams University, Cairo, Egypt, and Dr Homie Razavi and his team from the Polaris Observatory, the Center for Disease Analysis (CDA) Foundation, Lafayette, CO, USA, just 21 countries* are responsible for around 80% of these pediatric hepatitis C infections, with the highest prevalence rates generally found in developing countries.

    Mother to Child Transmission is one of the main causes of hepatitis C in children. However, neither pregnant women nor young children with this cancer-causing illness can be treated with the highly-effective direct-acting antiviral (DAA) medications. Various regulatory agencies such as the US FDA and the European Medicines Agency have now approved DAAs for use in children aged 12 years and over*. But in high-income countries, there is as yet little evidence they are being used in this age group. WHO is also yet to recommend DAA in any children regardless of age.

    As a result, almost all children are only treated with older pegylated interferon regimens, which often have severe side effects including stunting growth, influenza-like symptoms, anaemia and weight loss, and do not always cure the virus. Trials of DAA drugs in children under 12 years are also ongoing, but they have not been approved yet in any country for these younger children.

    “Currently, 4 million children are living with hepatitis C, which can be cured and 48 million with hepatitis B, which has a vaccine”, said Charles Gore, President of the World Hepatitis Alliance. “Enough is enough. Governments and global health organisations must ensure all children are vaccinated for hepatitis B and provided with DAAs for hepatitis C, and that all pregnant women are screened.”

    Compared to hepatitis C, new hepatitis B infections among children are declining -from approximately 4.7% prevalence in the pre-vaccination era of the early 1980s to 1.3% – due to scaled-up efforts to prevent mother-to-child transmission and global coverage with the three doses of hepatitis B vaccine. Currently, 84% of countries offer hepatitis B vaccinations. However, coverage with the initial birth dose vaccination needed to provide protection to newborns, is still low at 39%.

    Cases of hepatitis C in children are, however, likely to continue growing for years to come, given the lack of prevention and control programs for pregnant women living with hepatitis C and women of child bearing age. This is exacerbated by the absence of a public health approach for case definition and management of expectant mothers or children.

    “We must act and treat as many children as possible. The economic and social benefit of early hepatitis C treatment in children is substantial,” Professor El-Sayed explains. “This includes avoiding disease progression, removing social stigma and improving activity and school performance, and reducing fatigue. However, the fundamental principle is to avoid transmission by adopting ‘cure as prevention’ at an early age and before high risk behaviours emerge that enable transmission.”

    “Children are the future.” Peck concluded. “It’s imperative that we get it right from the beginning and give them the best possible start in life. Without eliminating viral hepatitis amongst children, its elimination will be impossible”.

     

    Read also:

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    Hepatitis C buyers’ clubs grow worldwide as a way to obtain affordable treatment http://www.eatg.org/news/hepatitis-c-buyers-clubs-grow-worldwide-as-a-way-to-obtain-affordable-treatment/ Tue, 07 Nov 2017 22:50:34 +0000 http://www.eatg.org/?post_type=news&p=6714 Hidden amongst the thousands of Facebook pages given over to holiday snaps and gossip are groups of patients who have hepatitis C, a disease that affects more than 70 million worldwide and kills around 400,000 people a year.

    But importantly, these groups of patients from Russia to Australia have got together to help each other import a relatively new class of drug that is able to cure most of the patients who take it.

    These buyers’ clubs, as they’re called, are reminiscent of a Hollywood film Dallas Buyers’ Club, where a group establishes to access cheaper HIV drugs.

    Dr James Freeman, who was behind the first hepatitis C buyers’ club in Australia and has consulted for others, said in an interview, “There are around a hundred of these around the world and the least one in every [high-income] country.”

    The reason that these buyers’ groups have popped up is because many of the hepatitis C drugs on offer in their own countries are extremely expensive. Most can’t access these drugs through their health systems and have now, controversially, taken to importing them from cheaper sources abroad.

    The originator companies that first brought these blockbuster drugs to market have offered them for has much as $84,000 for a 12-week course.

    Of course, many countries have now negotiated much lower prices with the companies that make the drugs.

    The problem is, prices are still not low enough to pay for everybody who has hepatitis C, according to governments, activists and many patients. As a result, only the sickest patients access the drugs, which are heavily rationed in many countries.

    And that’s why buyers have now begun to get together to import them from countries where they are much cheaper, said Dr Andrew Hill, a pharmacology expert from the University of Liverpool, United Kingdom. He spoke last week at the World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) and was to present data on the hugely varying cost of a 12-week course of sofosbuvir and daclatasvir, a common combination of such drugs, from $78 in India and $174 in Egypt, and US$6000 in Australia. but it is still $77,000 in the UK, and a staggering $96,404 the USA.

    “The negotiated prices of the drugs from originators are still far higher than prices available from generic companies, so there is still a big incentive for people to import the drugs,” he said. “Very few people are aware that this is legal in a range of countries such Australia and the UK.”

    Prices are so much lower in India and Egypt because generic companies sell them at close to cost price, according to Hill. They cannot sell their drugs within Europe, for example, because there is a patent.

    Speaking from Tasmania, FixHepC’s Freeman said buyers’ groups help individual patients source and buy from drug suppliers in India, Algeria and Egypt, often accessing laboratory tests to confirm their consignments are acceptable, and provide advice on taking the course of medication.

    Personal Use

    Buyers’ groups are relying on a loophole that allows them to import small amounts of medication for personal use from generics abroad.

    These so-called personal importation rules, were designed to allow patients to bring in small amounts of medication even if that medication has not been registered in the country; tourists can visit a country and bring their own medication, or foreign visitors can use their usual medication from home while working and living overseas.

    The buyers’ groups are basing their actions on a few elements of the TRIPS agreement (World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights). The most important, Article 60, states that small quantities of goods of a non-commercial nature contained in travellers’ personal luggage or sent in small consignments are permitted.

    Freeman said the size of “a small consignment” is not precisely defined within TRIPS but is usually interpreted within many national rules as under 2 kg.

    How such consignments are bought and paid for, however, must be managed extremely carefully. “If I bought the medications and sold them to patients that would be illegal. Only licensed pharmacists can sell medications,” he said.

    They work something like this: Buyers’ clubs act in the role of the patient’s agent. The buyer is the patient and they are exercising their rights, the seller is in the country of the medication’s origin and is operating within their laws, said Freeman. “Buyers’ clubs link the two – this is legal and no different from any other agent helping a person exercise a transaction,” he added. “So what buyers’ clubs do is de-risk the process, which is, after all a pretty uncommon way of getting a medication.”

    Interestingly, several governments from Uruguay to Denmark are relaxing or have relaxed their personal import rules to help patients access drugs from abroad. Switzerland, for example, allowed just one month’s worth of medication to be imported. That has been extended to 3 months.

    And at the end of March, Italian Minister of Health Beatrice Lorenzin issued a circular stating that patients and their doctors are allowed to import medicines authorised for sale in other countries for personal use when there is no therapeutic alternative authorised in Italy or when a treatment authorised in Italy is not accessible to patients due to restrictive prescription criteria or because it is too expensive for the patient.

    “She did this with only a veiled reference to the high-priced hepatitis C (HCV) medicine sofosbuvir, marketed under the trade name Sovaldi,” Ellen ‘t Hoen at the Global Health Unit Department of Health Sciences, UMCG Groningen, said on her Medicines Law and Policy blog at the time.

    But not all countries allow personal imports, however. The US is one example.

    That said, individual US states are understood to be discussing strategies to access hepatitis C drugs, some related to personal importation. Louisiana, for example, is mooting the idea of using an old federal law known as 28 USC 1498, which permits the government to directly purchase drugs without regard to their patent status.

    “The importation debate is really happening in the US as well, because the states cannot afford these hepatitis C treatments for their people,” said Tahir Amin, a lawyer at I-MAK, which is challenging the hepatitis C drug patents in various countries including the US.

    Gilead said it has been working with national healthcare systems toward the goal of enabling unrestricted access to its curative HCV treatments. “Patients in most developed countries have access to our curative HCV medicines via their national healthcare system and do not need to resort to unregulated and uncontrolled buyer’s clubs to receive treatment,” said a spokesperson.

    It said it is concerned with patient safety and that the patients cannot be sure what they are receiving through the clubs. “The source and quality of hepatitis C medicines secured through medical tourism and buyers’ clubs are unknown,” the spokesperson said.

    Nevertheless, patients worldwide are looking at alternative methods to access the drugs; Irish citizens unable to import drugs are getting on the ferries to buy them in the UK, said FixHepC’s Freeman. Before the import rules changed, Italians were nipping over to Vatican City for cheaper drugs too, said Paolo Corciulo, of Cure-HepC, a company that provides hepatitis C treatment services.

    He welcomes the changes, but says there are some drawbacks. For example, quite a bit of paperwork is required beforehand – such as an import request from an Italian doctor. “The main problem is that most of the doctors refuse to fill up the form. They don’t know the generic brand or they just don’t want responsibility,” he said.

    Additionally, there are no guidelines on how to deal with reputable dealers, which may expose unsuspecting patients to unscrupulous criminals, he warned. Corciulo has opted instead to take patients to the drugs – 200 have already been on Hep C holidays to India. Here patients can buy the drugs at source and are treated by doctors at reputable Indian hospitals.

    But many believe a more wide-reaching strategy is necessary. Countries such as Malaysia recently announced that it will override the patent, and issue a compulsory licence (CL) to import generics medicines so that more of its citizens can be treated.

    It is unclear which countries may follow, said the University of Liverpool’s Hill, although Thailand and Brazil have historically issued the most CLs.

    “The first step is for these countries to understand how much they could save by going down this path. Few countries realise just how cheaply these drugs can be made, and how much extra they are paying,” he said.

    By Tatum Anderson

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    Australia: Gonorrhoea and syphilis on the rise, HIV stable, and some good news on hepatitis http://www.eatg.org/news/australia-gonorrhoea-and-syphilis-on-the-rise-hiv-stable-and-some-good-news-on-hepatitis/ Tue, 07 Nov 2017 21:50:48 +0000 http://www.eatg.org/?post_type=news&p=6710 Australia’s annual report card on STIs and blood-borne viruses finds that gonorrhoea has increased by 63% over the past five years.

    Gonorrhoea and syphilis diagnoses are increasing in Australia, HIV is stable, and more than 30,000 Australians have been cured of hepatitis C, according to the latest Annual Surveillance Report on HIV, viral hepatitis and sexually transmissible infections (STIs) in Australia, released today (November 6) by the Kirby Institute at UNSW Sydney.

    The latest data shows that gonorrhoea has increased by 63% over the past five years, with particular rises among young heterosexual people in major cities.

    “Up until recently, gonorrhoea had been uncommon in young heterosexual people living in major cities. Rising rates in this group highlight the need for initiatives to raise awareness among clinicians and young people about the importance of testing,” said Associate Professor Rebecca Guy, head of the Surveillance, Evaluation and Research Program at the Kirby Institute. “With the national strategies for HIV, hepatitis and STIs up for review, reducing STIs in young people will be an important target.”

    Among Aboriginal and Torres Strait Islander peoples, chlamydia and gonorrhoea rates were three and seven times higher than in the non-Indigenous population and the gaps were greater in regional and remote areas. Since 2011, there has been a resurgence of infectious syphilis among young Aboriginal and Torres Strait Islander people living in regional and remote areas of Northern Australia.

    “Initiatives underway to address the syphilis resurgence include enhanced testing and treatment, and culturally appropriate health promotion campaigns,” said Associate Professor James Ward, head of Infectious Diseases Research, Aboriginal Health Infection and Immunity, South Australian Health and Medical Research Institute. “Comprehensive strategies are needed to reduce STIs in Aboriginal and Torres Strait Islander peoples.”

    HIV diagnoses stable for fifth year in a row

    The report shows that HIV diagnoses have remained stable in Australia for the past five years, with 1,013 new diagnoses in 2016.

    Associate Professor Guy said these results are due to high levels of testing and treatment in Australia. “We’re seeing increased uptake of HIV testing, particularly among gay and bisexual men, who are the population most affected by HIV in Australia,” said Associate Professor Guy. “It is also encouraging that 86% of people diagnosed with HIV were on treatment in 2016.”

    However, gaps in testing remain, particularly among heterosexual people, where one in five HIV diagnoses occurs. Nearly half of heterosexual people diagnosed with HIV were diagnosed late, meaning they were likely to have acquired HIV at least four years before diagnosis.

    “For HIV to decline nationally, we must focus on a combination of prevention strategies, including enhancing our testing and treatment efforts, making HIV self-testing available and ensuring equitable access to pre-exposure prophylaxis (PrEP) across Australia,” said Associate Professor Guy. PrEP is a treatment which prevents people at risk from acquiring HIV, but is currently only accessible through clinical trials.

    “A recent announcement from NSW Health shows early evidence of the impact of this combination of strategies, with a 31% reduction in new HIV diagnoses in gay and bisexual men in the first half of 2017 compared to the previous five years, the lowest count on record,” said Associate Professor Guy.

    In contrast, the report indicates that HIV diagnoses among Aboriginal and Torres Strait Islander people have increased by 39% since 2012, with a greater proportion of diagnoses due to injecting drug use and heterosexual sex, compared to non-Indigenous populations.

    Associate Professor Ward said that this disparity highlights the need for culturally relevant HIV prevention programs for Aboriginal people. “We need enhanced community education, targeted testing and treatment initiatives – including access to PrEP, and greater access to sterile needle and syringes, and drug dependence treatment for people who inject drugs.”

    Some good news on hepatitis, but more work to be done

    Between March and December 2016, an estimated 30,434 people have been cured of hepatitis C due to the availability of new direct acting antiviral therapy for hepatitis C.

    “The new therapies have been game-changing for hepatitis C in Australia”, said Associate Professor Jason Grebely from the Viral Hepatitis Clinical Research Program at the Kirby Institute.

    “Our estimates indicate that the number of people with hepatitis C who have advanced liver disease has fallen for the first time in 10 years. This is excellent news, but to achieve hepatitis C elimination in Australia we must sustain our efforts to ensure all people living with hepatitis C are tested and have access to these cures.”

    The report also shows that over the past five years hepatitis B diagnoses have declined by 27% in people aged less than 25 years, reflecting the impact of the infant and adolescent vaccination programs. However, only 63% of the estimated 230,000 people living with chronic hepatitis B in Australia by the end of 2016 were diagnosed. Of those, only 27% were having appropriate clinical monitoring tests for their infection.

    “The significant gaps in diagnosis and care highlight the need for better strategies to reach people living with hepatitis B in Australia,” says Associate Professor Ben Cowie, director of the WHO Collaborating Centre for Viral Hepatitis, Doherty Institute.

    The decline in hepatitis B diagnoses is also evident in younger Aboriginal and Torres Strait Islander peoples. “It is encouraging to see that immunisation programs for hepatitis B have had a clear benefit in reducing the gap in hepatitis B between Aboriginal and Torres Strait Islander people and the non-Indigenous population,” said Associate Professor Ward. “However, hepatitis B diagnoses in the population over 30 years remain high and a continued focus on testing and vaccination among this population is needed.”

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    Treating HCV in HIV-coinfection: still a therapeutic dilemma? http://www.eatg.org/news/treating-hcv-in-hiv-coinfection-still-a-therapeutic-dilemma/ Tue, 07 Nov 2017 19:36:51 +0000 http://www.eatg.org/?post_type=news&p=6702 All patients with HIV infection should be screened at least once for HCV. In patients with continued risk factors, such as injecting drug use or men who have sex with men, HCV screening should be repeated. Consequently, there are several treatment sensitivities that need to be taken into account when treating coinfected individuals.

    Read the full publication here.

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    HCV: Miracle cure costs less than a budget airline flight http://www.eatg.org/news/hcv-miracle-cure-costs-less-than-a-budget-airline-flight/ Mon, 06 Nov 2017 22:45:42 +0000 http://www.eatg.org/?post_type=news&p=6696 The revolution in generic drugs means that a 12-week course of drugs to cure hepatitis C can be manufactured for just US$50 – as low as the cost of a plane ticket on many low-cost airlines. Furthermore, new data shows that these generic copies are just as effective as the branded medicines. Yet restrictions and patent issues around the world mean that hardly any patients can access the drugs at these low costs, say experts speaking at the World Hepatitis Summit in Sao Paulo, Brazil (1-3 November).

    “As there are around 70 million people infected with hepatitis C worldwide, the basic cost of the drugs to treat everyone infected globally, at $50 each, would be around US $3.5 billion,” explains Dr Andrew Hill, a pharmacology expert from the University of Liverpool, UK. This represents less than a fraction of 1% of the global health budget of some US$ 8 trillion. “Much more must be done to enable all countries — but especially developing countries — to produce or buy drugs for these lower prices. Without significant changes to pricing structures, the battle against the global hepatitis C epidemic simply can’t be won.”

    In his presentation, Dr Hill will present data on the hugely varying cost of a 12-week course of sofosbuvir and daclatasvir, a common combination of the new directly acting antiviral drugs (DAAs) that have revolutionised hepatitis C treatment by providing rapid cure with few or no side effects. The list price for this combination of drugs ranges from close to cost price in India ($78) and Egypt ($174) to $6,000 in Australia, $77,000 in the UK, and a staggering $96,404 the USA. Yet the basic cost of the active ingredients, including formulation and packaging costs and even allowing a small profit margin for the generic companies brings the basic cost down to under $50 per course.

    In high-income countries, most of which have treatment restrictions allowing only those with advanced disease to be treated first, some infected patients have resorted to buying generic drugs from international buyers’ clubs (who buy in bulk from developing countries) or directly from countries where they are manufactured. For example, in the UK, those not wanting to wait for advanced disease to be treated have been able to legally purchase a 12-week generic course for prices ranging from US $1000 to $1200. Research studies on these patients show that cure rates are as high as for the branded medicines, ranging from 90% to 95%.

    An analysis presented at the summit on the efficacy of generic DAAs looked at 1160 patients who have imported DAAs for personal use into 88 countries on 5 continents. Data from these patients show that cure rates are well over 90%, the same as for the branded products, but at a fraction of the cost.

    “In 2016, for every person cured of hepatitis C globally (1.76 million), another person was newly infected (1.5 million). We simply cannot eliminate this epidemic unless we treat more people. And we can only do this if the prices of the drugs come down,” explains Dr Hill.

    He adds that the manufacturers of DAAs must do more to provide voluntary licences in countries that do not currently have them for generic companies to produce cheaper (but just as effective) generic DAAs. This is what has happened in Egypt, which had nearly 7 million people to treat, but now have fewer than 5 million. However, more than half of those people infected globally live in countries with no voluntary licence to allow generic production. “For example, China and Russia, two countries with very large hepatitis C epidemics, have no voluntary licence in place to produce cheap generic drugs,” explains Dr Hill.

    However, Dr Hill makes clear that any efforts to reduce drug prices and enable mass generic DAA production worldwide will be futile unless countries also step up their efforts to find and diagnose their infected populations. “We cannot treat people if we do not know who they are,” explains Dr Hill. “Countries must massively step up their screening efforts, or they will simply run out of people to treat – a diagnostic ‘burn-out’. The proportion of patients with hepatitis C who know they have it ranges from 44% in high-income countries to just 9% in low-income countries.”

    He concludes that lessons can and should be learned from the HIV epidemic to successfully end the hepatitis C epidemic worldwide. “It has taken the world 15 years to get 19 million people globally on antiretroviral treatments for HIV,” he says. “We already have the drugs necessary to eliminate hepatitis C. Let’s learn from the past, and repeat the medical success story of global HIV treatment.”

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    CoPE Call for Applications http://www.eatg.org/news/cope-call-for-applications/ Fri, 03 Nov 2017 09:25:11 +0000 http://www.eatg.org/?post_type=news&p=6645 We are pleased to announce a special CoPE call for hepatitis, addressing the need for access to hepatitis prevention, testing, treatment and care services by co-infected key populations. Please find below detailed information on how to apply for this grant. The submission deadline is Monday 30 November 2017 (23:59 CET).

    What is CoPE?
    The CoPE project is a funding mechanism that enables the production and translation of patient education materials, brochures and other resources related to HIV/AIDS & co-infections in multiple languages. More information about CoPE can be accessed here: www.eatgtrainingacademy.com/cope.

    Who can apply and receive a grant?

    Any community-based organisation in the European and Central Asian region dealing with prevention and treatment of HIV/AIDS and co-infections can submit an application to CoPE. The selection is based on the soundness of the proposed project and available funding.

    What type of publications are supported?
    CoPE supports publications which:

    • Promote necessary, objective, reliable and up-to-date knowledge and skills about HIV/AIDS and co-infections among patients, patient groups, groups at-risk, and healthcare providers;

    • Raise awareness and appreciation of facts and issues related to HIV/AIDS treatment among PLWH (such as women, men who have sex with men, injecting drug users, sex workers, migrant communities and other groups at-risk);

    • Offer objective, scientifically-accurate, high-quality, patient-focused and user-friendly overview and summary of relevant health and treatment information on specific and generic HIV-related topics and issues;

    • Engage, support and empower local HIV-positive community for the preparation and development of necessary and relevant treatment materials.

    • The final format of the resource may be a printed brochure, booklet, handout etc. or an online document/website.

    Specific focus for this call
    This call is specifically focused on the topic below. Applications dealing with other topics will not be considered during the selection process.

    • Applications addressing the need for access to hepatitis prevention, testing, treatment and care services by co-infected key populations. This includes publications that support the local community in better understanding HCV and HBV as co-infections.  

    Application procedure
    Please fill in and submit an application form online via this link:
    www.eatgtrainingacademy.com/application-form.
    Please fill in all the sections of the application form in English. Incomplete applications will not be considered.

    Submission Deadline
    The deadline for submission is Monday 30 November 2017 (23:59 CET).

    Notification of selection outcome
    The outcome of your application will be announced five weeks after the submission deadline.

    Before applying

    • Map the existing resources in the local language and in English/other languages. An archive of the materials previously funded by CoPE is available here.

    • Define if you would like to translate an existing publication or develop something entirely new.

      • For a translation, ask for authorization from the original author for the use of the material. Specify the eventual changes you would like to make to the original (adapting it to the local context).

      • For a new publication, develop a summary of the main topics and themes covered. Make sure you have access to leading expert(s) in the field who can guarantee the accuracy of the information.

    • Make a detailed cost estimate of the cost of production of the publication, including writing/translating, proofreading, design & layout, printing and dissemination. The estimate should be based on actual quotes from different service providers. Please note that, if accepted, the CoPE grant is paid in two instalments: first 50% when a print-ready document is submitted and the remaining amount upon receipt of financial and narrative reports (incl. copies of all invoices and receipts).

    • Please note that the maximum amount that is available for this call is 1,100 EUR. Applications requesting lower amounts will be considered favourably in the selection process.

    • Make a realistic timeline for the production process. Please note that, if accepted, the project should be finalized within 3 months (for translations) or 6 months (for new publications) from the signing of the grant agreement. The final grant amount may be decreased in case of delay caused by the grantee. Therefore, make sure you and your collaborators are ready to start working instantaneously if your application is approved.

    • Draft a dissemination plan. The publication should be widely promoted (locally, regionally and nationally) via different channels.

    Questions:
    If you have any questions regarding the CoPE project or the application form please contact Maria Dutarte (EATG Project Manager) at projects@eatg.org.

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    World Hepatitis Summit – Declaration of the Hepatitis Community http://www.eatg.org/news/world-hepatitis-summit-declaration-of-the-hepatitis-community/ Thu, 02 Nov 2017 22:52:18 +0000 http://www.eatg.org/?post_type=news&p=6638 The World Hepatitis Summit passed and published the Declaration of the Hepatitis Community “NO ELIMINATION WITHOUT DECRIMINALIZATION!” today. The Declaration calls for the decriminalization of people who use drugs, and the global upscale and support of prevention, harm reduction and treatment services available to them.

    It urges states “to remove all barriers to the uptake of the full range of prevention services by people who use drugs by reforming laws, law enforcement procedures and discrimination that hinder access, including the criminalization of minor, non-violent drug offences and to adopt an approach based overwhelmingly on public health promotion, respect for human rights and evidence”.

    The consortium of signatories was led by Medecins du Monde, and EATG has also been a member.

    Declaration website: http://www.medecinsdumonde.org/en/actualites/hepatite-c/2017/10/31/hepatitis-no-elimination-without-decriminalization

    Declaration in French: Hepatitis-declaration-FR

    Declaration in English: Hepatitis-declaration-EN

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    Global progress towards hepatitis C elimination still blocked by cost of treatment, lack of diagnosis http://www.eatg.org/news/global-progress-towards-hepatitis-c-elimination-still-blocked-by-cost-of-treatment-lack-of-diagnosis/ Wed, 01 Nov 2017 22:50:10 +0000 http://www.eatg.org/?post_type=news&p=6625

    Nine countries — Australia, Brazil, Egypt, Georgia, Germany, Iceland, Japan, the Netherlands and Qatar — are on course to eliminate hepatitis C by 2030, according to data released at the World Hepatitis Summit in São Paulo, Brazil, this week.

    The World Health Organization’s elimination target challenges countries to aim for a 90% reduction of new hepatitis B and C infections and a 65% reduction in hepatitis B and C related mortality by 2030.

    Estimates presented by the Polaris Observatory, developed from all available national data, show a stark contrast in progress towards HCV elimination in two of the world’s wealthiest countries, Australia and the United States.

    Low awareness and barriers to care in the United States

    According to the Polaris Observatory estimates just over half of people with hepatitis C in the United States are aware of their infection. Although rates of diagnosis are high in New York state (81%) and California (71%), other states are doing less well, and the United States is also experiencing a sharp increase in new hepatitis C infections in young adults and adolescents as a result of sharing of injecting equipment.

    In 2015, the USA treated around 256,000 patients and some 230,000 in 2016. Polaris’s latest projections suggest that without new initiatives to boost treatment and diagnosis rates the annual number treated across the USA will fall to just 130,000 per year by 2020. To reach the WHO 2030 elimination target, treatment levels must be sustained at 250,000 per year leading up to 2030. The USA is also unlikely to meet the targets set out in its own national plan, some of which are even more ambitious – such as a 60% fall in both hepatitis B and hepatitis C new infections by 2020.

    In two thirds of states, treatment on Medicaid programs has been restricted to people with advanced disease, preventing treatment access for those without private insurance. However, the outlook is not entirely bleak — recent developments have meant the approval of new and cheaper hepatitis C drugs, which can be used to treat all types of the virus (genotypes 1-6), requiring just 8 weeks of treatment to achieve cure.

    These lower prices are allowing states such as Delaware, which previously restricted treatment to the sickest patients, to open up Medicaid coverage to all hepatitis C patients from January 2018. Delaware joins 16 other states (including Alaska and Georgia) that will open up restrictions (or never had them).

    At the recent Liver Meeting in Washington, DC (October 28) all states and Puerto Rico were graded on how easy it is to obtain Medicaid treatment for hepatitis C. States receiving the best grade of A were Alaska, Connecticut, Massachusetts, Nevada, and Washington. States that received an “F”, the worst grade, were Arkansas, Louisiana, Montana, Oregon, and South Dakota.

    Australia

    The Australian government responded to the call for universal access to the hepatitis C DAAs with an AUS $1billion dollar investment over 5 years. This risk-sharing agreement with pharmaceutical companies provides government-funded treatment to all adults without restriction and has paved the way for the elimination of hepatitis C by 2030. More than 30,000 patients with hepatitis C were treated and cured in 2016.

    Following this agreement, huge numbers of people came forward for treatment immediately (some 5,000 in March 2016 alone). However, the number treated each month has steadily declined, from over 5,000 in March 2016 to less than 2,500 in March 2017, with signs the number will decrease further still.  The Polaris estimate shows that Australia must treat around 20,000 patients with hepatitis C per year to reach the WHO elimination target it endorsed (a reduction of new hepatitis B and C infections by 90% and mortality by 65% by 2030). Polaris predicts annual treatment numbers for HCV could fall to 14,000 by 2018.

    “Australia set off at a cracking pace on the journey to elimination of hepatitis C due to our unrestricted and easy access to treatment,” says Helen Tyrell, Chief Executive Officer, Hepatitis Australia. “From March 2016, when the cures became available, to December of that year around 14% of all people living with hepatitis C commenced treatment. However, the pace has slowed dramatically over time.”

    She adds: “Worryingly, the latest estimates from the Polaris Observatory should be taken as a clear warning that the elimination of hepatitis C is unlikely to be achieved by 2030 if we continue ‘business as usual’. What we need now is a rapid scale up of a suite of programs to help connect all people with hepatitis C to the new cures while also continuing to prioritise evidence-based prevention. Provided Australia invests in this work and maintains a strong partnership approach across government, the community, clinicians and researchers, we can reach the goal of elimination of hepatitis C by 2030.”

    By Keith Alcorn

     

    Read also:

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    Countries risk ‘running out’ of hepatitis C patients to treat, says World Hepatitis Alliance http://www.eatg.org/news/countries-risk-running-out-of-hepatitis-c-patients-to-treat-says-world-hepatitis-alliance/ Wed, 01 Nov 2017 22:45:52 +0000 http://www.eatg.org/?post_type=news&p=6630 The latest data on the global hepatitis C epidemic, released at the World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) reveal that most countries (especially high-income countries) are running out of patients to treat because of the low diagnosis rates worldwide.

    Globally, just one in five patients with hepatitis C knows they are infected (14 million out of 69 million). The proportion ranges from 44% across high-income countries down to just 9% across low-income countries. And while a record 1.76 million people with hepatitis C were treated in 2016, countries cannot hope to achieve elimination without boosting diagnosis rates.

    “Hepatitis C is a silent killer and there are nearly 70 million people worldwide who need treatment, but we must find them,” said Charles Gore, President of the World Hepatitis Alliance. “Yet, because of the historic lack of national and international investment in viral hepatitis programmes, the vast majority of patients with hepatitis C – some 80% –remain undiagnosed, and less than 5% are able to access treatment.”

    The data, released by the CDA Foundation’s Polaris Observatory* (led by Dr Homie Razavi in Lafayette, CO, USA), show that new diagnoses of hepatitis C must triple from 1.5 million to 4.5 million each year and treatment rates from 1.76 million to 5 million in order achieve WHO’s elimination targets by 2030.

    “We have the right to know if we are living with a cancer-causing virus” said Raquel Peck, CEO of World Hepatitis Alliance. “In addition to the need for people to be diagnosed to access treatment, a high proportion of the 1.5 million new hepatitis C infections last year could have been avoided if people were aware of their health status.”

    To confront this challenge a number of countries are using innovative strategies to improve their diagnosis rates, from testing at dental appointments and in hospital emergency rooms to screening entire villages, alongside offering financial incentives.

    In Egypt, the entire village of El Othmanya (population 3,500 people) was screened, with 215 cases of hepatitis C detected. So far, this same methodology has now been extended to 50 villages in 26 regions of Egypt, as the country targets screening 30 million of its 90 million population by the end of 2018.

    In New Zealand’s remote Northland region, the local health board provided NZ$300 to general practices for each patient successfully diagnosed and treated for hepatitis C infection, allowing them to waive the co-payment fees that patients are required to pay for doctors’ appointments. The New Zealand government has also recently announced a nationwide programme to pay the medical transport costs of all people with hepatitis C.

    In Chicago, USA, Mount Sinai Hospital ran a program up to March 2017 that automatically screened any patient over 16 years entering the emergency department and needing blood tests. This resulted in a diagnosis of nearly 200 patients with hepatitis C in the six-month program.

    Emergency room screening is also helping detect some 70% of new cases in the Cherokee Nation American Indian Tribe in Oklahoma, USA, which has its own elimination plan. All patients visiting the doctor or the dentist are also offered a test for hepatitis C.

    “Only with a combination of political will, increased access to diagnostics and greater awareness of the disease can we vastly improve diagnosis rates,” says Dr Razavi. “Unless we crack this diagnosis challenge, the ambitious elimination targets for hepatitis set by WHO will remain out of reach for decades to come.”

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    UK elimination of hepatitis C in jeopardy unless more patients found http://www.eatg.org/news/uk-elimination-of-hepatitis-c-in-jeopardy-unless-more-patients-found/ Wed, 01 Nov 2017 22:40:19 +0000 http://www.eatg.org/?post_type=news&p=6624 New data show that more than 100,000 people living with hepatitis C in the UK are undiagnosed

    Just one in three people with hepatitis C in the United Kingdom have been diagnosed according to the latest estimates released at this year’s World Hepatitis Summit in São Paulo, Brazil (1-3 November).

    The estimate comes from a global synthesis of data on hepatitis C prevalence and diagnosis carried out by the Polaris Observatory, led by Dr Homie Razavi. The Polaris Observatory study shows that out of an estimated 162,000 people living with hepatitis C in the UK, only 62,200 (38%) are diagnosed.

    “Even these numbers overestimate how many people are available for treatment because the majority of the ‘diagnosed’ are not in touch with services for a variety of reasons”, says Charles Gore, CEO of the national hepatitis C charity, The Hepatitis C Trust, and also President of the World Hepatitis Alliance.

    “Many were diagnosed years ago. They were never informed how deadly hepatitis C can be and they do not know about the new drugs and how extraordinarily effective and easy to take they are.”

    The poor rates of diagnosis in the United Kingdom call into question the possibility of achieving the World Health Organization target of hepatitis CV elimination by 2030, according to Dr Razavi.

    “To make the 2030 elimination target, at least 10,000 patients need to be treated each year, and there are already signs that it is becoming harder to find diagnosed patients to treat” said Dr Razavi. “Although in 2016 some 10,000 people were treated and in 2017 this could reach 12,500, the projections suggest the annual total will drop to an estimated 5,000 patients treated per year by 2020 without better diagnosis and linkage to care.”

    When direct-acting antivirals were introduced in the United Kingdom treatment was tightly rationed in order to contain costs. As a result of large price reductions negotiated with pharmaceutical companies it has been possible to expand the number of people treated, but according to the World Hepatitis Alliance, some areas are already running out of patients to treat. Having vetoed 2 years ago a Hepatitis C Improvement Framework designed to improve diagnosis and linkage to care, the NHS is now scrabbling to put in place initiatives to do just that.

    According to Public Health England’s most recent report on hepatitis C, the number of tests carried out for hepatitis increased by around 20-25% between 2011 and 2015. Public Health England suggests that the World Health Organization’s European target of diagnosing 50% of people with hepatitis C by 2020 has already been met in England and Wales, and points to a high rate of testing among people who have ever injected drugs, the group with the highest HCV prevalence in England and Wales.

    But, although HCVB prevalence is high among people who have injected drugs, anyone exposed to blood in the past could be infected. People who received blood transfusions or blood products prior to the introduction of screening in the United Kingdom in 1992, and people who have received blood or undergone medical procedures in countries with lower infection control standards, could be living with undiagnosed hepatitis C.

    “We have at least 100,000 people to find,” says Charles Gore. “If we don’t find them, not only will we never reach the goal of elimination, but significant numbers will die. To be honest, with these new drugs available, if anyone dies of hepatitis C, it should be viewed as an appalling failure of the system.”

    By Keith Alcorn

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    Only half of people in USA living with curable cancer-causing disease are aware http://www.eatg.org/news/only-half-of-people-in-usa-living-with-curable-cancer-causing-disease-are-aware/ Wed, 01 Nov 2017 19:34:51 +0000 http://www.eatg.org/?post_type=news&p=6631 New data released at this year’s World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) show that out of an estimated 2.7 million (1) people now living with hepatitis C in the US, only just over half (55%) are aware, contributing to increasing infection rates and poor treatment outcomes. This means that the US is very unlikely to meet either the WHO hepatitis elimination target* or its own national targets set out in the National Viral Hepatitis Action Plan 2017-2020 (2).

    Hepatitis C is a ‘silent killer’, accounting for around 23,000 deaths across the US in 2016, a figure that is rising each year. In 2007, mortality related to hepatitis C surpassed that of HIV in the US; and since 2012, hepatitis C-related deaths have surpassed deaths from all the other 60 nationally reportable infectious diseases combined. Only half of people living with the disease are aware of their condition, largely due to the disease being mostly asymptomatic and the lack of routine screening. The result for many is a missed opportunity to access the highly effective cures that can stop them succumbing to liver disease, cirrhosis and liver cancer and can cure them of the virus entirely.

    Risk factors for hepatitis C infection include injection drug use past or present, including steroids, medical or dental procedures abroad, unsterile tattoos and piercings, and blood transfusions for any reason before 1992 when the US began screening all donated blood for hepatitis C.

    These latest data from The Polaris Observatory, Center for Disease Analysis Foundation, Lafayette, CO, USA (led by Dr Homie Razavi and his team) reveal that, like other high-income countries, the USA is facing a problem with diagnosis, although state level data from the six states for which Polaris has data show that diagnosis rates are above the national estimate of 55%: Rhode Island (60%); Ohio (61%); Louisiana (64%); California (71%); Washington (76%) and New York (81%). However, even these are not high enough to enable enough patients to enter treatment.

    “Despite the different levels of diagnosis across the US, there are also problems linking people to care,” said Dr Homie Razavi. “The fact is that even when people are diagnosed, they are not being referred and often don’t get treated,” adding that “there are many possible reasons for patients not accessing treatment.”

    Among these reasons are that, in two thirds of states (3), treatment on Medicaid programs has been restricted to people with advanced disease, preventing treatment access for those without private insurance. Some patients (and doctors) may not view treatment as a priority due to lack of symptoms and disease progression. Some people may not be aware of the short and generally side effect-free treatment (direct acting antivirals [DAAs]) now available. And others may be lost in the system or out of reach of care providers, including injection drug users.

    In 2015, the USA treated around 256,000 patients and some 230,000 in 2016. Polaris’s latest projections suggest that without new initiatives to boost treatment and diagnosis rates the annual number treated across the USA will fall to just 130,000 per year by 2020. To reach the WHO 2030 elimination target, treatment levels must be sustained at 250,000 per year leading up to 2030. The USA is also unlikely to meet the targets set out in its own national plan, some of which are even more ambitious – such as a 60% fall in both hepatitis B and hepatitis C new infections by 2020.

    Another issue facing the USA is the explosion of new infections faced by certain states caused by the opioid crisis, with steep increases in young white men and women in certain urban areas. As a result, the CDC reports a 250% increase in new HCV cases from 2011-2014, and reported infections are now at a 15-year high. However, most people do not know they are infected and thus many new infections go unreported. The new data from Polaris suggests almost 38,000 people contracted hepatitis C in 2016 alone. All states are at risk in the opioid crisis, which has just been declared a national public health emergency by US President Donald Trump.

    “Policymakers are starkly aware of the heroin-fentanyl epidemic sweeping America,” said Michael Ninburg, President Elect of the World Hepatitis Alliance. “They also need to be aware of the resulting ballooning hepatitis C infections in certain states, most notably amongst young adults and adolescents, and be proactive about diagnosing and treating those in need.”

    Across the USA, certain populations continue to face an enormous struggle to access hepatitis C drugs, including prisoners and people who inject drugs. An estimated 1 in 6 prisoners has HCV, but access to new treatments is severely restricted by prison budgets. And although some critics may argue that people who inject drugs may not be suitable for hepatitis C treatment that requires a daily pill, recent studies3 have reported cure rates equal to those in other people with HCV. Thus the central issue for people who inject drugs is to be diagnosed and start treatment, not whether or not treatment works.

    However, the outlook is not entirely bleak — recent developments have meant the approval of new and cheaper hepatitis C drugs, which can be used to treat all types of the virus (genotypes 1-6), requiring just 8 weeks of treatment to achieve cure. At $26,400 per course, this combination of 2 drugs glecaprevir and pibrentasvir (made by AbbVie) is cheaper than courses of similar hepatitis C medications ($55,000-95,000).

    These lower prices are allowing states such as Delaware, that previously restricted treatment to the sickest patients, to open up Medicaid coverage to all hepatitis C patients from January 2018. Delaware joins 16 other states (including Alaska and Georgia) that will open up restrictions (or never had them). At the recent Liver Meeting in Washington, DC (October 28) all states and Puerto Rico were graded on how easy it is to obtain Medicaid treatment for hepatitis C. States receiving the best grade of A were Alaska, Connecticut, Massachusetts, Nevada, and Washington. States that received an “F”, the worst grade, were Arkansas, Louisiana, Montana, Oregon, and South Dakota (4).

    For patients with private insurance, it has generally (but not always) been much easier to obtain hepatitis C treatment. However, as many of these patients may have already accessed care and been cured, the pool of patients to treat is rapidly declining.

    Similarly, at a state level, various initiatives are ongoing to boost diagnosis rates. In New York State, a 2014 law required primary care providers to test all people born 1945-1965 for hepatitis C. This increased the number of tests in this age group from 538,229 in 2013 to 813,492 in 2014, a 51% rise. The proportion of newly diagnosed patients who were then linked to care also increased by a third state-wide.

    In Chicago, USA, Mount Sinai Hospital automatically tested anyone over 16 needing blood tests in the emergency room for 6 months, resulting in 200 new diagnoses. Emergency room screening is also helping detect some 70% of new cases in the Cherokee Nation in Oklahoma, which has its own hepatitis C elimination plan. All patients visiting the doctor or the dentist are also offered a test for hepatitis C.

    Ninburg concludes: “We have the tools to eliminate hepatitis C in the US. We have effective cures for hepatitis C, and also effective vaccination to prevent hepatitis B. Now we just have to make ending hepatitis a political priority and prevent hundreds of thousands of needlessly premature deaths.”

    ###

    Notes to editors:

    1 2.7 million is the latest estimate of total chronic HCV cases requiring treatment in 2016 across the whole of the USA, produced by the Polaris Observatory, continuing on from their 2015 estimate. The Polaris Observatory is the source used by WHO for regional and global estimates on hepatitis C, based on the latest modelling and data available. Although this is considerably lower than the US CDC estimate of 3.5 million in 2010 (source Edlin 2015), the new Polaris estimate also incorporates the changing population after 2010 due to deaths*, new infections*, and cure (an estimated 684,000 cured from 2010-2016, based on treatment data from IMS Health and standard SVR rates).

    For USA data and projections, see: http://tonykirby.com/hepatitis/PolarisDataUSA2017.xlsm

    2 For details of the US National Viral Hepatitis Action Plan 2017-2020, see: https://www.hhs.gov/hepatitis/action-plan/u-s-viral-hepatitis-action-plan-overview/index.html

    3 the PREVAIL sand SIMPLIFY studies have been recently presented at scientific meetings and are due for publication. Both show cure rates above in injectiob drugs users of 90-95%, similar to those in other persons with HCV.

    4 the latest Medicaid report card, released at the Liver Meeting in Washington, DC, on Monday October 23, shows the latest situation regarding treatment restrictions in all states. Please see: https://stateofhepc.org/report/

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    Close to 3 million people access hepatitis C cure http://www.eatg.org/news/close-to-3-million-people-access-hepatitis-c-cure/ Tue, 31 Oct 2017 19:20:05 +0000 http://www.eatg.org/?post_type=news&p=6615 World Hepatitis Summit 2017 calls for accelerated action to eliminate viral hepatitis

    31 October 2017 | São Paulo, Brazil On the eve of the World Hepatitis Summit in Brazil, WHO reports increasing global momentum in the response to viral hepatitis. A record 3 million people were able to obtain treatment for hepatitis C over the past two years, and 2.8 million more people embarked on lifelong treatment for hepatitis B in 2016.

    “We have seen a nearly 5-fold increase in the number of countries developing national plans to eliminate life-threatening viral hepatitis over the last 5 years,” says Dr Gottfried Hirnschall, Director of WHO’s Department of HIV and Global Hepatitis Programme. “These results bring hope that the elimination of hepatitis can and will become a reality.”

    Hosted by the Government of Brazil, the World Hepatitis Summit 2017 is being co-organized by WHO and the World Hepatitis Alliance. The Summit aims to encourage more countries to take decisive action to tackle hepatitis, which still causes more than 1.3 million deaths every year and affects more than 325 million people.

    “We cannot lose sight of the fact that last year 194 governments committed to eliminating viral hepatitis by 2030. For sure we are still a long way from this goal but that doesn’t mean it’s some unattainable dream. It’s eminently achievable. It just requires immediate action,” says Charles Gore, President of World Hepatitis Alliance. “The World Hepatitis Summit 2017 is all about how to turn WHO’s global strategy into concrete actions and inspire people to leave with a ‘can do’ attitude.”

    “Brazil is honored to host the World Hepatitis Summit 2017 – and welcomes this extraordinary team of experts, researchers, managers and civil society representatives to discuss the global health problem posed by viral hepatitis,” says Dr Adele Schwartz Benzaken, Director of the Brazilian Ministry of Health’s Department of Surveillance, Prevention and Control of STIs, HIV/AIDS and Viral Hepatitis.”Brazil is committed to taking recent advances in its response to hepatitis forward – on the road to elimination.”

    Progress in treatment and cure

    Many countries are demonstrating strong political leadership, facilitating dramatic price reductions in hepatitis medicines, including through the use of generic medicines—which allow better access for more people within a short time.

    In 2016, 1.76 million people were newly treated for hepatitis C , a significant increase on the 1.1 million people who were treated in 2015. The 2.8 million additional people starting lifelong treatment for hepatitis B in 2016 was a marked increase from the 1.7 million people starting it in 2015. But these milestones represent only initial steps – access to treatment must be increased globally if the 80% treatment target is to be reached by 2030.

    However, funding remains a major constraint: most countries lack adequate financial resources to fund key hepatitis services.

    Diagnosis challenge

    To achieve rapid scale-up of treatment, countries need urgently to increase uptake of testing and diagnosis for hepatitis B and C. As of 2015, an estimated 1 in 10 people living with hepatitis B, and 1 in 5 people living with hepatitis C, were aware of their infection. Countries need to improve policies, and programmes to increase awareness and subsequent diagnosis.

    Prevention gaps

    Countries need to provide a full range of hepatitis prevention services that are accessible to different population groups, particularly those at greater risk.

    Largely due to increases in the uptake of hepatitis B vaccine, hepatitis B infection rates in children under 5 fell to 1.3% in 2015, from 4.7% in the pre-vaccine era.

    However, the delivery of other prevention services, such as birth-dose vaccination for hepatitis B, harm reduction services for people who inject drugs, and infection control in many health services, remains low. This has led to continuing rates of new infections, including 1.75 million new hepatitis C cases every year.

    Need for innovation

    Innovation in many aspects of the hepatitis response must continue. New tools required include a functional cure for hepatitis B infection and the development of more effective point-of-care diagnostic tools for both hepatitis B and C.

    “We cannot meet the ambitious hepatitis elimination targets without innovation in prevention interventions and approaches, and implementing them to scale,” said Dr Ren Minghui Assistant Director-General for Communicable Diseases, WHO. “The great successes of hepatitis B vaccination programmes in many countries need to be replicated and sustained globally in the context of moving forward to universal health coverage.”

    Implementation of elimination strategy

    The World Hepatitis Summit 2017 will be attended by over 900 delegates from more than 100 countries, including Ministers of Health, national programme managers, and representatives from organizations of people affected by viral hepatitis. The Summit will review progress and renew commitments by global partners to achieve the elimination of viral hepatitis by 2030 – a target reflected in WHO’s elimination strategy and the UN Sustainable Development Goals.

     

    Fact sheets

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    MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag http://www.eatg.org/news/msf-secures-generic-hepatitis-c-treatment-at-120-compared-to-147000-launch-price-tag/ Tue, 31 Oct 2017 19:15:36 +0000 http://www.eatg.org/?post_type=news&p=6617 Geneva/Sao Paolo, 31 October 2017—On the eve of the World Hepatitis Summit in Sao Paolo, the international medical humanitarian organization Médecins Sans Frontières (MSF) today announced that it had secured deals for generic hepatitis C medicines for as low as US$1.40 per day, or $120 per 12-week treatment course for the two key medicines sofosbuvir and daclatasvir.

    In the US, pharmaceutical corporation Gilead launched sofosbuvir at $1,000 per pill in 2013, and Bristol-Myers Squibb (BMS) launched daclatasvir at $750 per pill in 2015, leading to the original price tag of $147,000 for a person’s 12-week combination treatment course. The corporations have also been charging exorbitant prices in many developing countries, paralyzing the launch of national treatment programs and causing treatment rationing in many countries around the world.

    “What good is a breakthrough medicine that people cannot afford?” asked Jessica Burry, Pharmacist for MSF’s Access Campaign. “Pharmaceutical corporations price hepatitis C medicines far out of reach for people paying out of pocket around the world, and also for many governments struggling to provide treatment in the public sectors; but the prices for generic versions keep coming down. Governments must use every tool in their toolbox to fight for access to lower-priced generics so they can scale up treatment for the millions of people who need it; they should follow the lead of countries like Malaysia and issue compulsory licenses when patents block people’s access to this life-saving treatment.”

    In 2015, MSF started procuring sofosbuvir and daclatasvir from Gilead and BMS through their ‘access programs’ at a price of $1,400 to $1,800 per 12-week treatment. Today, MSF pays a fraction of that, at $120, sourced from quality-assured generic manufacturers.

    An estimated 71 million people have chronic hepatitis C infection worldwide, 72 per cent of whom live in low- and middle-income countries. Direct-acting antiviral medicines (DAAs) represent a treatment breakthrough for people with hepatitis C, with cure rates of up to 95%, and with far fewer side effects than previous treatments. Yet access to DAAs has remained limited because pharmaceutical corporations charge unaffordable prices, leading many countries to reserve treatment only for people with the most advanced stages of the disease. By the end of 2016, three years after sofosbuvir was launched, only an estimated 2.1 million people globally had been treated with the medicines, leaving 69 million people still without access.

    These high prices have also put a major strain on health systems in wealthy countries, in particular those enacting universal health care. Treatment is being rationed in countries such as Australia, Canada, Italy and the US, in addition to developing countries, and is a stark reminder of the early days of HIV treatment.

    “Almost two decades ago, MSF and others worked hard to get access to generics and bring down prices for HIV medicines,” said Mickael Le Paih of MSF in Cambodia, where MSF treats people living with hepatitis C. “History is repeating itself with hepatitis C—the medicines we need are again too expensive, but we are finding ways to make treatment affordable so that our patients can be cured.”

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    Hepatitis C test-and-treat programme reduces HCV by two-thirds among men who have sex with men in Swiss HIV Cohort http://www.eatg.org/news/hepatitis-c-test-and-treat-programme-reduces-hcv-by-two-thirds-among-men-who-have-sex-with-men-in-swiss-hiv-cohort/ Tue, 31 Oct 2017 14:38:10 +0000 http://www.eatg.org/?post_type=news&p=6611

    A systematic policy of test-and-treat cured 99% of men who have sex with men with hepatitis C in the Swiss HIV Cohort in an 8-month period and reduced the prevalence of hepatitis C by almost two-thirds, Dominique Braun of the University Hospital, Zurich, reported at the 16th European AIDS Conference (EACS 2017) last week in Milan.

    Dr Braun was presenting results of the Swiss HCVree trial, a non-randomised study of hepatitis C virus (HCV) testing, treatment and behavioural counselling designed to eliminate chronic HCV infection in men who have sex with men with HIV/HCV co-infection in the Swiss HIV Cohort.

    The Swiss HIV Cohort has seen a 20-fold increase in the prevalence of HCV in men who have sex with men since 1996, with the greatest increase occurring since 2008, in common with other western European countries.

    Reducing onward transmission and prevalence of HCV requires a reduction in the number of people with chronic HCV infection and a reduction in risk behaviours. Chemsex – especially the use of drugs and sharing of injecting equipment during sex – and group sex are strongly implicated in the increase in hepatitis C in men who have sex with men.

    In an 8-month period between October 2015 and May 2016 all men who have sex with men in the Swiss HCV Cohort were screened for active HCV infection. Screening identified 177 men with chronic HCV infection (4.8%) of which 147 had been diagnosed previously. Thirty new and previously undiagnosed HCV infections were diagnosed as a result of the screening exercise.

    All men with genotype 1 or 4 infection were offered immediate treatment with a course of grazoprevir/elbasvir (Zepatier) for 12 or 16 weeks depending on baseline resistance, with additional ribavirin for all genotype 1a and 4 patients with previous experience of pegylated interferon and ribavirin, for previously untreated genotype 1a patients with baseline NS5A resistance mutations and genotype 1b patients with prior HCV protease inhibitor experience.

    Of the 177 people diagnosed with chronic HCV infection, 122 took part in the study (34 received treatment elsewhere, 11 had a genotype other than 1 or 4, 6 had contraindications for treatment and the remainder were either lost to follow-up or unwilling to take part in the study).

    Men who joined the trial had a median age of 46 years, 88% were white and all but one was taking antiretroviral therapy. Participants had been diagnosed with HCV a median of three years before joining the study and 79% had F0-F1 stage fibrosis, indicating little liver damage since infection. Six per cent had F3-F4 stage fibrosis.

    The predominant genotypes were 1a (67%) and 4 (26%), with 7% having genotype 1b infection. HCV RNA was relatively low at baseline (865,279 IE/ml).

    All participants except one achieved a sustained virologic response and was cured of hepatitis C infection. The exception was a previously untreated man with genotype 4 infection who experienced viral rebound after treatment.

    Treatment was well tolerated with no serious drug-related adverse events. Drug-related adverse events were reported in 29% of participants and were predominantly fatigue, diarrhoea, nausea and itching.

    Preventing onward transmission and reinfection

    Sixty-eight men recruited to the study reported condomless sex with non-regular partners. Of these men, 51 agreed to take part in a four-session behavioural intervention devised by Professor Dunja Nicca of Zurich University that accompanied the treatment phase of the study.

    The first session focused on emotional responses to safe sex problems, the second on individualised solutions, the third on developing a personal risk reduction plan and the fourth session a reflection on the post-treatment achievement of hepatitis C cure and how to maintain it.

    The study found that 65% of men reported condomless anal intercourse as a potential risk factor for acquiring HCV; only 30% reported sharing injecting equipment or other equipment for snorting drugs and 29% reported sharing sex toys or fisting as potential risk factors. Forty out of 51 reported drug use, mainly methamphetamine (43%) and GBL or GHB (57%)

    The overall completion rate of the behavioural intervention was 90%. No cases of reinfection have been identified to date.

    By Keith Alcorn

    References

    Braun D et al. High SVR12 rates with grazoprevir/elbasvir +/- ribavirin for 12-16 weeks guided by genotypic resistance testing among HIV/HCV coinfected MSM in the Swiss HCVree trial. 16th European AIDS Conference, 25-27 October, Milan, abstract PS9/4, 2017.

    Nicca D et al. Doing the impossible: an e-health-assisted counselling intervention to reduce risk in HCV-reinfection in men who have sex with men. 16th European AIDS Conference, 25-27 October, Milan, abstract PE25/24, 2017.

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    High rate of hepatitis C reinfection in German men who have sex with men http://www.eatg.org/news/high-rate-of-hepatitis-c-reinfection-in-german-men-who-have-sex-with-men/ Tue, 31 Oct 2017 14:35:52 +0000 http://www.eatg.org/?post_type=news&p=6610

    Around one in seven gay and bisexual men cured of hepatitis C at major treatment centres in Germany has become reinfected since 2014, according to findings from the German Hepatitis C Cohort presented on Friday at the 16th European AIDS Conference (EACS 2017) in Milan.

    At least half of these men became reinfected within a year of completing treatment and all reinfections occurred within 18 months.

    The risk of reinfection is thought to be highest among men who share drug injecting equipment during sex – chemsex – but Dr Stefan Mauss of the Center for HIV and Hepatogastroenterology in Dusseldorf said that sharing drug injecting equipment during sex might explain only a quarter of these cases of reinfection.

    People infected with hepatitis C who are cured of the infection are vulnerable to reinfection. Although a proportion of people will cure hepatitis C infection spontaneously, it is not clear if a successful response to previous treatment increases the likelihood of clearing hepatitis C virus (HCV).

    Several studies with varying periods of follow-up have looked at the risk of reinfection among men who have sex with men in Europe.

    A study in London carried out prior to the introduction of direct-acting antiviral treatment found an incidence of reinfection of 9.6 cases per 100 person-years of follow-up.

    More recently, a multicentre study in western and central Europe found an incidence of reinfection of 7.3 per 100 person-years. The study also found big variations between cities.

    The German Hepatitis C Cohort collects information on everyone treated with direct-acting antivirals at nine treatment centres in Germany. In this analysis, investigators reviewed reinfection rates among 1533 people who had been cured of hepatitis C and compared rates of reinfection according to potential risk factors.

    Thirty-two cases of reinfection were identified, all in men. Five cases occurred in men who injected drugs (an incidence of 0.96%). Twenty-seven cases occurred in men who have sex with men (an incidence of 13.1%). Only seven of the men who have sex with men said that they had used intravenous drugs, suggesting either a discomfort about disclosing drug use or predominantly sexual transmission.

    Reinfection occurred fairly soon after completing treatment, in a median of 53 weeks (range 36-70 weeks).

    In almost half of cases (44%) the reinfection was a new genotype.

    A study of acute HCV infections at one of London’s largest sexual health and HIV clinics, the Mortimer Market clinic, found that among 95 people diagnosed with acute HCV infection between 2015 and 2017, 27% reported condomless anal intercourse as their only risk factor. Almost all those acutely infected with HCV were men who have sex with men (94%) and only 27% reported injecting drugs.

    Almost a quarter of the infections (22 cases) occurred in people who were HIV negative, leading presenter Emily Chung to recommend that risk-based screening for HCV infection should now be considered for HIV-negative men who have sex with men.

    By Keith Alcorn

    Reference

    Ingiliz P (S Mauss presenting). High incidence of HCV reinfection in HIV-positive MSM in the DAA era. 16th European AIDS Conference, 25-27 October, Milan, abstract PS9/1, 2017.

    Chung E et al. Acute hepatitis C infections in men who have sex with men: changing patterns of risk. 16th European AIDS Conference, 25-27 October, Milan, abstract PE15/1, 2017.

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    EACS 2017: NATAP reports http://www.eatg.org/news/eacs-2017-natap-reports/ Tue, 31 Oct 2017 14:14:47 +0000 http://www.eatg.org/?post_type=news&p=6607 The 16th European AIDS Conference (EACS 2017) took place on 25-27 October 2017 in Milan, Italy.

    NATAP reports:

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    Fatty liver common after direct-acting antivirals for hep C http://www.eatg.org/news/fatty-liver-common-after-direct-acting-antivirals-for-hep-c/ Tue, 31 Oct 2017 13:32:57 +0000 http://www.eatg.org/?post_type=news&p=6614 WASHINGTON, DC — Evidence of steatosis is found in almost half the patients with hepatitis C who achieved a sustained virologic response after treatment with direct-acting antivirals, results from a prospective study show.

    “Fatty liver is very common now that hepatitis C is being treated effectively,” said Mazen Noureddin, MD, from Cedars-Sinai Medical Center in Los Angeles.

    American and European guidelines state that a patient can be discharged from care in the absence of cirrhosis and elevated liver enzymes, but “we wanted to see what happens after direct-acting antiviral treatment,” he said.

    Steatosis was “very prevalent” in the study population, “although liver enzymes were normal,” Dr Noureddin reported here at The Liver Meeting 2017.

    Monitoring people for steatosis after a sustained virologic response is not common practice, he told Medscape Medical News, but these findings suggest that long-term monitoring is warranted.

    Long-term Monitoring Needed

    In their study, Dr Noureddin and his colleagues compared transient elastography findings (FibroScan, Echosens) in 101 patients — 49 men and 52 women — before and after they were treated with direct-acting antivirals. After each participant achieved a sustained virologic response, the researchers used the controlled attenuation parameter (CAP) to assess liver fat.

    Mean age of the participants was 60 years and mean body mass index (BMI) was 28 kg/m². In addition, 36% of the patients were white, 25% were Hispanic, and 90% had diabetes. The hepatitis C infection was genotype 1 in 86% of the patients, genotype 2 in 13%, and genotype 4 in 1%. People with genotype 3 infection were excluded from the analysis because the etiology of hepatic steatosis is different in this population.

    Decreases were significant in alanine transaminase (ALT) and aspartate transaminase (AST) levels and fibrosis scores from baseline to the achievement of sustained virologic response (P < .05).

    In the study cohort, 48% of the patients showed evidence of steatosis after treatment, 6% of whom had advanced fibrosis. None of the 52% of patients without steatosis showed evidence of advanced fibrosis, defined as a score of at least 11 kPa.

    For patients with steatosis, weight did not change during the study period. However, there were significant differences between these patients and those without steatosis.

    Table. Mean Values After Patients Achieved a Sustained Virologic Response

    Parameter Patients With Steatosis Patients Without Steatosis P Value
    BMI 29 m/kg² 26 m/kg² <.05
    Glucose level 108 mg/dL 96 mg/dL <.05
    ALT level 20 mg/dL 15 mg/dL <.05
    CAP score 297 dB/m 214 dB/m <.05
    Fibrosis score 7.0 kPa 5.3 kPa <.05

    “We need more follow-up,” said Dr Noureddin. “We looked at patients 48 weeks after treatment. Next, we want to follow patients longitudinally to see if more patients with a fatty liver also develop fibrosis.”

    “This is one of the most important studies presented at this meeting,” said Naim Alkhouri, MD, from the Texas Liver Institute in San Antonio.

    “The treatment of chronic hepatitis C infection has been revolutionized by the introduction of highly effective direct-acting antivirals, with cure rates of 95% or higher,” he told Medscape Medical News. “However, the study showed that even after achieving a cure for hepatitis C, approximately 50% of those patients demonstrated evidence of NAFLD, which may increase their risk for liver cirrhosis and liver cancer.”

    “The use of FibroScan with CAP to assess for the presence of NAFLD and fibrosis progression should be considered in patients who are cured from hepatitis C infection,” Dr Alkhouri said.

    Dr Noureddin is a speaker and advisor for EchoSense. Dr Alkhouri has disclosed no relevant financial relationships.

    The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD): Abstract 2155. Presented October 23, 2017.

    By Damian McNamara

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    Hepatitis C halved in Spanish people living with HIV in one year due to treatment http://www.eatg.org/news/hepatitis-c-halved-in-spanish-people-living-with-hiv-in-one-year-due-to-treatment/ Sat, 28 Oct 2017 12:02:31 +0000 http://www.eatg.org/?post_type=news&p=6592

    Spain is making dramatic progress towards eliminating hepatitis C in people living with HIV because of widespread use of direct-acting antivirals, Juan Berenguer of Hospital Gregorio Marañón, Madrid, reported on Friday at the 16th European AIDS Conference (EACS 2017) in Milan.

    Sampling patients at 43 clinics in Spain, researchers found that the proportion of people living with HIV who have chronic hepatitis C virus (HCV) infection has fallen dramatically since 2009, from approximately one-third of all patients in care to 11.7% of all patients in late 2016. In just one year, from late 2015 to late 2016, the prevalence of chronic hepatitis C in people living with HIV fell by 47%, from 22% to 11.6%.

    The Spanish health care system has been providing direct-acting antiviral treatment for hepatitis C to everyone with F2 grade fibrosis or above since early 2016 and provides direct-acting antiviral treatment to anyone who might transmit HCV, regardless of fibrosis stage.

    The GeSIDA network of Spanish researchers carried out a cross-sectional study to evaluate the effect of improved treatment access on the prevalence of HCV co-infection in people with HIV in Spain. They sampled patients from 43 HIV treatment centres in Spain in proportion to their patient population, taking a random sample from each clinic. The total population in care was 38,904 in October and November 2016 (the sample period) and the random sample comprised 1588 patients, of whom 35% were men who have sex with men and 29.6% were people who had acquired HIV through injecting drug use.

    This sample was compared with previous samples in 2002, 2009 and 2015.

    Whereas 60.8% of those sampled had HCV antibodies in 2002, this proportion had declined to 34.6% by 2016. Similarly, the proportion with chronic HCV infection (HCV RNA positive) fell from 54% in 2002 to 34% in 2009 and 11.7% in 2016.

    In part this can be explained by the declining proportion of the sample who had acquired HIV through injecting drug use: 55.2% in 2002, and 29.6% in 2016.

    However, the study also found that the proportion who had ever received HCV treatment rose from 23% in 2002, 48% in 2009, and 59.3% in 2015 to 74.7% in 2016. Of the 548 people who had HCV antibodies in the 2016 sample, 292 (53.2%) had been cured of hepatitis C. Of the remaining 186 people with chronic infection, 41 were undergoing treatment at the time of the survey, suggesting that if 95% were cured, HCV RNA prevalence could have been as low as 9.1%.

    HCV continuum EuroSIDA

    Only half of people with diagnosed HIV/HCV co-infection in Southern Europe have ever started a course of treatment to cure hepatitis C infection, and less than 40% in Central and Eastern Europe, an analysis of people receiving HIV care in the European region shows.

    The findings, also presented to EACS 2017 on Friday, by Sarah Amele of University College London, come from the EuroSIDA study, an amalgamation of HIV treatment cohort studies in Western, Central and Eastern Europe.

    The study was designed to evaluate the continuum of care for hepatitis C in people with HIV/HCV co-infection, from testing to treatment, who were in care in January 2015.

    The researchers identified 6985 people in the EuroSIDA cohort with a positive HCV antibody test result prior to January 2015. Of these, 79% had a subsequent test for HCV RNA to diagnose chronic infection – meaning that almost one in five did not receive a test to determine whether or not they had active HCV infection. HCV RNA testing is an essential first step in determining whether a person with HCV antibodies is in need of treatment for HCV infection. People with HCV antibodies who have a negative HCV RNA are presumed to have cleared the infection spontaneously.

    HCV RNA testing occurred much less frequently in Eastern Europe than in Western Europe: only 46.4% received an HCV RNA test in Eastern Europe compared to 93.7% in Western Europe.

    People from migrant communities were less likely to receive an HCV RNA test but people who inject drugs were more likely to receive an HCV RNA test than the population as a whole.

    Of the entire population of people with HCV antibodies, 5027 had a positive HCV RNA result and 57.4% of all people with HCV antibodies remained HCV RNA positive in January 2015.

    Of those who tested HCV RNA positive, 45.3% had an HCV genotype test.

    Less than half of all those diagnosed with chronic infection had undergone any course of treatment by January 2015 (45.3%) and in the overwhelming majority of cases the treatment consisted of interferon and ribavirin. Only 9.4% received a course of interferon-free treatment with direct-acting antivirals.

    Although 2079 people completed a course of treatment, the outcome of treatment was documented for only 1305 people due to lack of virological testing during and after treatment.

    Just 285 people with chronic infection were cured of HCV in the period up to January 2015, approximately 5% of all those diagnosed with chronic infection.

    Overall, the study found that substantial proportions of people were being lost at each stage of the care continuum and that access to treatment remained poor for people living with HIV.

    By Keith Alcorn

    References

    Amele S et al. The hepatitis C continuum of care among HIV-infected individuals in EuroSIDA. 16th European AIDS Conference, 25-27 October, Milan, abstract PS9/1, 2017.

    Berenguer J et al. HIV/HCV coinfection in Spain: elimination is a stone’s throw away. 16th European AIDS Conference, 25-27 October, Milan, abstract PS9/3, 2017.

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    US: HCV rates double in pregnancy, up risk for vertical transmission http://www.eatg.org/news/us-hcv-rates-double-in-pregnancy-up-risk-for-vertical-transmission/ Sat, 28 Oct 2017 08:47:42 +0000 http://www.eatg.org/?post_type=news&p=6594 Researchers in one US state have reported almost a doubling in the proportion of pregnant Medicaid recipients who had hepatitis C virus (HCV) infection, with obvious implications for vertical transmission of the virus from mother to child.

    They explain that the exponential increase in hepatitis C among women of childbearing age is attributed to the opioid crisis in the United States.

    “Fueled by the increase in injection drug use ensuing from the opioid epidemic, the proportion of infants born to HCV-infected women is increasing nationwide,” say Theresa Watts, MPH, and colleagues in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report, published online October 27.

    “Vertical transmission is the most common mechanism of HCV infection for children, reported to occur in approximately 6% of infants born to women with HCV infection, and approximately twice as often in women who are coinfected with HCV and human immunodeficiency virus (HIV),” they explain.

    But they also found that only a third of newborns in the state, Wisconsin, were tested for HCV infection.

    “Improvements in HCV screening practices among pregnant women and infants could enhance identification of infants at risk for vertical transmission of HCV,” they stress.

    Substantial Gap in Monitoring Infants at Risk for HCV Vertical Transmission

    The aim of the current study was to estimate the proportion of women enrolled in Wisconsin Medicaid with HCV infection during pregnancy and estimate the frequency of HCV testing and infection in infants born to HCV-infected women.

    Maternal name and date of birth from HCV reports in the Wisconsin Electronic Disease Surveillance System were linked to Wisconsin Medicaid data for 2011–2015 births.

    During this period, in the Wisconsin Medicaid population, the proportion of women who had evidence of HCV infection during pregnancy increased 93%, from 1 in 368 pregnancies to 1 in 192.

    But only 34% of the infants born to women with evidence of HCV viremia during pregnancy were tested for HCV according to recommendations, “revealing a substantial gap in monitoring infants at risk for HCV vertical transmission,” the researchers say.

    Mother-to-infant vertical transmission was documented in 4% of infants (7 of 183 born to women with evidence of HCV viremia during pregnancy).

    “Clinical signs of pediatric HCV infection often manifest slowly and can range in severity from being asymptomatic to fatal; liver transplantation is sometimes required,” the authors note.

    The current recommendation for identification of HCV during pregnancy is for risk-based screening.

    Pregnancy and postpregnancy care are ideal times to test women and link those with infection to HCV care or treatment because these are times when women typically use healthcare services, the authors explain.

    However, “unlike other bloodborne infectious diseases that have a risk for vertical transmission, such as hepatitis B virus or HIV, for HCV there is no perinatal intervention available that has been shown to reduce vertical HCV transmission,” they note.

    But presence of maternal HCV viremia (HCV RNA positivity) is a risk factor thought to increase the likelihood of vertical HCV transmission.

    “To improve surveillance of HCV vertical transmission, support identification of cases, and evaluate health outcomes of infected infants,” it would be pertinent for state and local health departments to follow guidelines issued in a recent position statement for reporting and national notification of perinatal HCV infection, issued by the Council of State and Territorial Epidemiologists

    “Adoption of this position statement…along with enhanced identification of HCV among women of childbearing age, can improve care for HCV-infected women and infants at risk for HCV vertical transmission,” the study authors conclude.

    The authors have disclosed no relevant financial relationships.

    MMWR Morb Mortal Wkly Rep. Published online October 27, 2017. Full text

    By Troy Brown

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    New three-drug HCV regimen shows nearly 100% response in 6, 8 weeks http://www.eatg.org/news/new-three-drug-hcv-regimen-shows-nearly-100-response-in-6-8-weeks/ Thu, 26 Oct 2017 18:19:05 +0000 http://www.eatg.org/?post_type=news&p=6584 WASHINGTON — A novel triple therapy combination correlated with nearly perfect SVR12 rates in most patients treated for 6 or 8 weeks, according to findings presented at The Liver Meeting 2017.

    “There is evidence that any shortening of treatment for hepatitis C may have potential to improve patient compliance, convenience, and tolerability,” Stefan Zeuzem, MD, of J. W. Goethe University, Frankfurt am Main in Germany, said. “The doses were chosen from a prior phase 2a study.”

    Zeuzem and colleagues presented findings for a three-drug combination called JNJ-4178 that includes the NS5B inhibitor AL-335 (Achillion) at 800 mg, the NS5A inhibitor odalasvir (Achillion) at 25 mg, and Olysio (simeprevir, Janssen) at 75 mg once daily. Researchers followed eligible participants for 24 weeks after the end of treatment.

    SVR12 served as the primary endpoint, and adverse events, laboratory abnormalities, electrocardiogram or echocardiogram, and pharmacokinetics served as secondary endpoints.

    The study included 183 patients treated for 6 weeks and 182 treated for 8 weeks. HCV genotypes 1a and 1b comprised approximately 70% of the cohort, with genotypes 2 and 4 comprising about one-quarter and a small proportion having genotype 5 HCV. “We extended the genotypes to the phase 2b study,” Zeuzem said. “All genotypes but genotype 6 were enrolled. They were allowed to be enrolled.”

    For the 8-week arm, 178 of 182 patients reached the primary endpoint, according to Zeuzem. In the 6-week arm, 181 of 183 patients reached SVR12. Zeuzem noted that these findings translated to an overall 98.9% SVR12 rate. “This of course also meets the non-inferiority to historical controls,” he said.

    SVR12 rates were above 98% in every genotype except genotype 2, Zeuzem added. “Specifically, genotype 2c infection patients experienced relapses most frequently,” he said.

    There were no grade 4 adverse events reported, no premature discontinuations of the study drug, and no laboratory abnormalities observed, according to Zeuzem. “There were typical adverse events, fatigue, headache, but nothing special in particular,” he said. “Extensive and thorough cardiac evaluation did not reveal any evidence for cardiotoxicity.”

    There is some debate about the role of resistance variants in patients who failed to reach SVR12, particularly those with genotype 2 disease, according to Zeuzem. Most of the variants were found in patients with genotype 2c.

    “Six and 8 weeks of treatment with [JNJ-4178] resulted in SVR rates of 99% and 98%, respectively,” Zeuzem concluded.

    By Rob Volansky

    For more information:

    Zeuzem S, et al. Abstract 65. Presented at: The Liver Meeting; Oct. 20-24, 2017; Washington, D.C.

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    Vical announces joint development program with AnGes on a treatment for chronic hepatitis B infection http://www.eatg.org/news/vical-announces-joint-development-program-with-anges-on-a-treatment-for-chronic-hepatitis-b-infection/ Wed, 25 Oct 2017 20:01:04 +0000 http://www.eatg.org/?post_type=news&p=6566 SAN DIEGO, Oct. 24, 2017 — Vical Incorporated (Nasdaq:VICL) announced today that it is pursuing early stage development of a novel treatment for chronic hepatitis B virus (CHB) infection based on its DNA and lipid-delivery technologies. This development effort is being conducted in collaboration with Vical’s strategic partner, AnGes, Inc of Osaka, Japan. The initial stage of this program will be to demonstrate preclinical proof of concept for inhibiting HBV infection in a human liver model in the second half of 2018. The ultimate aim of this program would be to demonstrate eradication of persistent HBV infection in CHB patients.

    AnGes has provided partial funding for the initial stage of this program and, if successful, Vical expects that AnGes will continue to participate in the funding of the program. AnGes has been granted the right of first refusal to negotiate with Vical for an exclusive license to develop and commercialize this therapy in Japan.

    Vical intends to first establish in vitro proof of concept against HBV infection using an HBV-producing cell line followed by in vivo testing in an elaborate preclinical model of HBV infection which enables human hepatocytes to be infected with HBV and then treated and monitored for suppression of several virologic markers including reduction in covalently-closed circular (ccc) DNA levels in the livers. Should Vical establish in vivo proof of concept, it intends to advance the product towards Phase 1 testing, ideally in CHB patients, to achieve clinical proof of concept at an early stage of development. Results of the preclinical proof of concept studies are anticipated in the second half of 2018.

    About chronic HBV infection

    Chronic HBV infection affects nearly 250 million people worldwide and an estimated 786,000 deaths are attributed annually to CHB infection worldwide. People with CHB infection are at increased risk for severe liver disease, with 15% to 40% developing cirrhosis or hepatocellular carcinoma. Although currently-available antiviral drugs effectively inhibit the HBV reverse transcriptase and suppress viral replication while the drugs are taken, they typically lead to only a 1% to 3% per year cure rate. The persistence of cccDNA in infected liver cells is not altered by the antiviral drugs so novel treatments are necessary to eliminate this reservoir and produce a long term cure, thereby reducing the need for lifelong antiviral drug use. Vical’s approach is intended to address the underlying cause of persistent HBV infection – cccDNA– by targeting hepatocytes and using molecular interventions to inactivate the cccDNA harbored within hepatocyte nuclei.

    About Vical

    Vical develops biopharmaceutical products for the prevention and treatment of chronic or life-threatening infectious diseases, based on its patented DNA delivery technologies and other therapeutic approaches. Additional information on Vical is available at www.vical.com.

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    ContraVir announces National Institutes of Health funded study on antiviral activity of CRV431 http://www.eatg.org/news/contravir-announces-national-institutes-of-health-funded-study-on-antiviral-activity-of-crv431/ Wed, 25 Oct 2017 19:58:01 +0000 http://www.eatg.org/?post_type=news&p=6565 EDISON, N.J., Oct. 24, 2017 — ContraVir Pharmaceuticals, Inc. (NASDAQ:CTRV), a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies, announced today that it will utilize preclinical services from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to characterize the antiviral activity of CRV431 in a humanized mouse model of hepatitis B virus infection.

    NIAID-funded contractor KMT Hepatech Inc. provides in vivo research services utilizing the proprietary platform technology of the KMT™ Mouse, also known as the chimeric mouse. KMT™ mice have livers that consist mostly of human liver cells and are now the model of choice for a variety of human liver diseases, including hepatitis. The planned study will examine CRV431 in KMT’s state-of-the-art animal model of hepatitis B virus (HBV) treatment efficacy.

    “We are pleased to work with KMT through the preclinical services program supported by the NIH,” said Dr. Robert Foster, Chief Scientific Officer of ContraVir. “We are particularly excited about using the KMT humanized mouse model, with its unique advanced methodology, for testing CRV431 anti-HBV activity. Given the historical absence of animal models of HBV infection that are both practical and that reflect the natural route of infection of human liver cells, the chimeric mouse has been a major advance. This study will further characterize CRV431 in vivo to determine its pharmacokinetics and measure HBV DNA and other viral markers of antiviral activity.”

    About CRV431

    CRV431 is a non-immunosuppressive analog of cyclosporine A (CsA) whose primary biochemical action is inhibition of cyclophilin isomerase activity, playing a key role in protein folding. Other viruses, such as HIV-1 and HCV, similarly use cyclophilin for their replication. CRV431 shows potential in experimental models to complement current hepatitis B treatments by reducing multiple markers of infection including HBV DNA, HBsAg, HBx, HBeAg, and HBV uptake by cells. Studies have also demonstrated that CRV431 possesses anti-fibrotic activity which may further curb progression of liver disease in patients.

    About ContraVir Pharmaceuticals

    ContraVir is a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies with a specific focus on developing a potentially curative therapy for hepatitis B virus (HBV). The Company is developing two novel anti-HBV compounds with complementary mechanisms of action. TXL™ currently in Phase 2, is designed to deliver high intrahepatic concentrations of TFV, while minimizing off-target side-effects caused by high levels of circulating TFV. CRV431, the other anti-HBV compound, is a next-generation cyclophilin inhibitor with a unique structure that increases its potency and selective index against HBV. ContraVir is also developing Valnivudine™, an orally available nucleoside analogue prodrug; Valnivudine™ is currently in Phase 3 for the treatment of herpes zoster. In addition to direct antiviral activity, Phase 2 data suggest that Valnivudine™ has the potential to reduce the incidence of debilitating shingles-associated pain known as post-herpetic neuralgia (PHN). For more information visit www.contravir.com.

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    News from The Liver Meeting® 2017 http://www.eatg.org/news/news-from-the-liver-meeting-2017/ Tue, 24 Oct 2017 20:15:19 +0000 http://www.eatg.org/?post_type=news&p=6540 The Liver Meeting® is the annual meeting of the American Association for the Study of Liver Diseases (AASLD). This year’s meeting took place on 20-24 October 2017 in Washington, DC.

     

    AASLD press releases:

     

    Pharma companies press releases:

     

    MedPage Today reports:

     

    Aidsmap reports:

     

    Healio reports:

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    New perspectives on risk of HIV and hepatitis among injecting drug users http://www.eatg.org/news/new-perspectives-on-risk-of-hiv-and-hepatitis-among-injecting-drug-users/ Tue, 24 Oct 2017 18:10:50 +0000 http://www.eatg.org/?post_type=news&p=6544 Reviews of the global prevalence of injecting drug use and of interventions to prevent the spread of blood-borne viruses among people who inject drugs paint a worrying picture.

    The provision of programs to prevent the spread of HIV and hepatitis among people who inject drugs (PWID) is inadequate in many countries around the world and presents a critical public health problem, comprehensive reviews by Australian researchers from the National Drug and Alcohol Research Centre at UNSW Sydney have found.

    The two reviews of the global prevalence of injecting drug use and of interventions to prevent the spread of blood borne viruses among PWID are published today in leading international journal The Lancet Global Health.

    The authors estimate that 15.6 million people have recently injected drugs. Of these, 18% are living with HIV infection and 52% test positive for hepatitis C (HCV) antibody.

    Yet despite evidence that needle and syringe programs (NSP) and opioid substitution therapy (OST) reduce HIV and HCV infections, they are still not being implemented in many places, and few people can access them in many countries, the authors found.

    Australia is one of only four countries worldwide with high coverage of both NSP and OST – the others are Austria, the Netherlands and Norway.

    In Australasia, 1.1% of PWID are living with HIV compared with 25% of PWID in Eastern Europe, 36% in Latin America, 18% in Sub Saharan Africa and 19% in South Asia.

    By contrast, the prevalence of hepatitis C among PWID is more evenly spread – 57% of the people who inject drugs in Australia and New Zealand test positive for hepatitis C antibodies, compared with 64% in Central Europe, 55% in North America and 50% in East and South-East Asia.

    “Across all countries, a substantial number of people who inject drugs are living with HIV or HCV and are exposed to multiple adverse risk environments that increase health harms,” says UNSW’s Professor Louisa Degenhardt, lead author of the paper reviewing prevalence of injecting drug use and HIV and hepatitis in this population.

    The reviews of global prevalence of injecting drug use and of provision of programs to prevent the spread of blood borne viruses are the first to be conducted since 2008, although the results are not directly comparable due to different and more sophisticated data collection techniques, and better country-specific record keeping.

    Evidence of injecting drug use was found in an additional 33 countries compared with the last review – predominantly from Sub Saharan Africa.

    Just over half (52%) of the countries with evidence of injecting drug use had needle and syringe programs. Medical treatment to encourage reductions in injecting – opioid substitution therapy – was available in less than half of all countries identified (48%).

    capture.png

    Opioid substitution therapy (OST) per 100 people who inject drugs. Graphic: Evan Cunningham/NDARC

    UNSW’s Dr Sarah Larney, lead author of the paper on global coverage of interventions, says: “Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics.

    “The presence of interventions alone is not sufficient; the greatest prevention benefits are reported when NSP and OST are implemented in high coverage and in combination,” Dr Larney adds.

    The three regions worldwide with the highest populations of people who inject drugs, East and South-East Asia, Eastern Europe and North America, all had poor provision of needle syringe programs and opioid substitution therapy.

    HIV prevalence in these countries was high, ranging from 9% in North America to 25% in Eastern Europe. By contrast, only 1% of people who inject drugs in Australia and New Zealand are living with HIV.

    “Several countries in these regions have experienced recent HIV outbreaks as well as persistently high HCV prevalence among PWID,” write the authors.

    For example, Russia, which has almost 2 million people who inject drugs – nearly 30% of whom have HIV and 69% of whom have hepatitis C – does not provide OST and has very limited access to NSP, the authors found.

    Interactive dashboards containing data from this study are available on the NDARC website.

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    Health experts warn UK politicians that chemsex is leading to a rise in hepatitis C http://www.eatg.org/news/health-experts-warn-uk-politicians-that-chemsex-is-leading-to-a-rise-in-hepatitis-c/ Tue, 24 Oct 2017 18:07:44 +0000 http://www.eatg.org/?post_type=news&p=6552 They say gay men need a health promotion campaign similar to the ‘tombstone’ HIV adverts of the 1980s to raise awareness

    Health experts in the UK have called for a national campaign similar to the AIDS tombstone advert to end the hepatitis C epidemic and stigma about the virus.

    Politicians in Westminster were told yesterday that the lethal combination of stigma, low public awareness and cuts to sexual health services have created a national epidemic with the LGBTI community in the UK particularly at risk.

    The All-Party Parliamentary Group (APPG) on Liver Health, which is holding an inquiry into hepatitis C, was told that less than 40% of people who are carrying the killer virus know that have it.

    Public Health England estimate around 160,000 people carry the virus.

    Chemsex risk

    People become infected through blood-to blood contact, poorly sterilized medical or tattoo equipment, intravenous drug use, blood transfusions and sexual contact. It can be cured by anti-viral drugs but if left untreated it can cause cirrhosis of the liver and liver cancer.

    The rise of chemsex, particularly among gay men, is among the factors for the rise in cases.

    David Stuart, Substance Misuse Lead at the 56 Dean Street sexual health center in London is one of the UK’s experts on chemsex.

    He told the meeting that gay men using mephedrone was an issue: ‘There has been an increase in injecting drug use among gay men. We’ve not seen a large increase but there has been an increase. There are issues around chemsex which we need to address.’

    Testing for the virus was critical but Stuart warned cuts to services were having a direct impact.

    ‘The reason we can’t beat the epidemic is we’re not getting people who are infected or carriers. It’s because we’ve been capped with numbers. Six sexual health clinics have closed in London over the last few months. We’ve had a rush of people who used to test elsewhere,’ he said.

    ‘It’s like closing A&E units. Trusts are closing more of the testing centers and encouraging people to test at home. It’s a terribly frightening test – the stigma of the disease – to do at home.’

    Among the sexual health clinics to close in London in the last six months are the clinic at the Royal Free in Hampstead, and two in South London run by Guy’s and St Thomas’ NHS Trust.

    ‘Around 40% of the infected population are aware’

    Dr Ian Brew, viral hepatitis lead at Leeds Teaching Hospital Trust, also called for an end to clinic closures and for the government to scale-up work to prevent the disease.

    Dr Brew, who is also responsible for HM Leeds Prison, said: ‘Sexual health clinics are very important. If we up-scaled what we are doing, that would be 7,000 extra people being treated just in prisons. If you multiply that out to other settings that would make a big difference.’

    He added people who are in middle age and unaware of their condition pose the biggest risk: ‘Things are a lot better than they were. But it’s estimated around 40% of the infected population are aware and unfortunately a lot more needs to be done.’

    Dr Brew warned: ‘The problem is if we don’t treat those patients now, they will become cirrhotic. There is a big saving: we know the cost of two years’ hospital care will be £65,000. So we know it’s effective.’

    ‘The parallels with HIV are amazing’

    Professor David Goldberg, consultant at Health Protection Scotland said HIV had only been tackled after the government committed to funding prevention work for 10 years.

    He said: ‘The parallels with HIV are amazing. That dedicated funding lasted for 10 years. That made a difference.’

    Stuart warned stigma in the LGBTI community about hepatitis C also had to be tackled. ‘We’ve got to address the stigma. It’s not “I hate you,” it’s “I feel sorry for him but I won’t have sex with him.” In a sexualized community, it’s quite a devastating diagnosis. The stigma is much worse than HIV. There’s not a lot of support within the community.’

    The panel, which included Baroness Masham and Labour MP Virendra Sharma, was told a national campaign similar to the tombstone TV advert made by the government in 1987 to raise awareness of AIDS and HIV was now needed.

    Dr Brew said: ‘We all remember the tombstone adverts for HIV. Something along those sort of lines would be a very good thing to raise awareness.’

    Dr Brendan Healy, chair of the Welsh Viral Hepatitis Sub Group, gave his support to the call for a campaign: ‘It’s a good way to encourage people to come forward. We’ve got to find people from a range of groups. I don’t think advertising would cost a significant amount of money. We could do something like the tombstone advert.’

    Stuart said: ‘We can never talk about it enough. That’s a good thing.’

    ‘We are now as a result seeing a concerning spike in hepatitis C cases’

    All of the experts said given current funding and priorities, the government would fail to meet its target to eliminate the hepatitis C in England by 2030.

    Stuart told the group: ‘We could beat this epidemic quite easily. I know it’s a money thing but it will pay off.’

    Dr Healy said: ‘This cannot be achieved through a rationed approach. Money is obviously an issue.’

    Havering is one of the London boroughs that is currently consulting on closure of its sexual health services and moving to a home-testing scheme.

    Cllr Alex Donald, Founder of Havering LGBT+ Forum told Gay Star News: ‘Having warned locally that closing STI centers would impact on public health, we are now as a result seeing a concerning spike in Hepatitis C cases.

    ‘With the majority of people not even knowing they have the virus, the Government must now rethink closing sexual health centers and invest in long-term solutions.’

    In a report published in March, Public Health England said that the number of people with hepatitis C in England had remained stable over the last decade, but that, ‘we need to do more to reduce the persistently high proportion who remain undiagnosed if levels of avoidable premature mortality are to be reduced.’

    GSN has approached the Department of Health for comment.

    By Chris Smith

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    Evidence supports link between hepatitis E, nerve disorder http://www.eatg.org/news/evidence-supports-link-between-hepatitis-e-nerve-disorder/ Tue, 24 Oct 2017 11:23:16 +0000 http://www.eatg.org/?post_type=news&p=6543 Certain European patients who presented with nontraumatic neurologic injury had evidence of hepatitis E. These patients showed similarities to other HEV-associated cases of neuralgic amyotrophy, suggesting a causal relationship, according to the researchers.

    “My colleagues and I have noticed, we find some patients presenting primarily with a neurological illness who don’t have much in the way of abnormality in the liver blood test,” Harry R. Dalton, MD, from the University of Exeter, United Kingdom, told Healio.com/Hepatology. “This study was exploring the notion of hepatitis E virus being misnamed, because these patients have a profound neurological injury, but not much of a hepatitis — it was a preliminary study looking at whether this virus might be neurotropic or not. And there is some laboratory evidence to support that it might be.”

    The cohort comprised 464 patients enrolled from England, France, and the Netherlands. Mean patient age was 63 years (range, 17-99 years). Eleven patients had evidence of current or recent HEV infection, all genotype 3, and seven had HEV RNA recovered from serum.

    “This was just a pilot study,” Dalton said. “Basically, we called it ‘operation blunderbuss’ because it was a bit of a blunt instrument; we decided to test all-comers presenting with non-traumatic acute neurology to secondary care and test for hepatitis E.”

    The researchers observed several neurological events among those with evidence of HEV, including cerebrovascular accident (n = 4), neuralgic amyotrophy (n = 3), seizure (n = 3), encephalitis (n = 1) and cranial nerve palsies (n = 1).

    Lasting neurological outcomes included minor sensory deficit, residual visual field defect, residual functional deficits, residual tinnitus, residual right-sided weakness, residual left-sided weakness and minimal deficits at 6 months, among seven patients, respectively. Regarding the other four patients, one recovered, one recovered completely, one returned to work after 6 months, and one recovered with recurrence at 6 months.

    According to the researchers, the prevalence of HEV viremia in the cohort was 1.5%, which was at least 10 times higher than the prevalence recently documented in blood donors in England (0.035%), France (0.045%) and the Netherlands (0.17%).

    The three patients with neuralgic amyotrophy and HEV had detectable HEV viremia at presentation. All three patients had bilateral asymmetrical involvement in the brachial plexus, which was previously associated with neuralgic amyotrophy in patients with HEV.

    “In all patients with neuralgic amyotrophy, all patients with Guillain-Barré syndrome, and all patients with encephalitis, they should have their hepatitis E status checked, irrespective of their liver blood test abnormalities,” Dalton concluded. “In other patients with neurology, I think it would be wise to consider it because we have not completely pinned it down what conditions might be associated to an all-cause. I think in the first three conditions I mentioned, there is very good evidence for causality. Hepatitis E is not just a hepatotropic virus, it can cause neurologic injury, so beware.”

    Dalton HR, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.07.010.

    By Talitha Bennett

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    Hepatitis C cure leads to improved quality of life http://www.eatg.org/news/hepatitis-c-cure-leads-to-improved-quality-of-life/ Mon, 23 Oct 2017 21:55:53 +0000 http://www.eatg.org/?post_type=news&p=6529

    People who were cured of hepatitis C with direct-acting antivirals (DAAs) had sustained improvements in their health-related quality of life, including both physical and mental health measures, according to study results presented at the AASLD Liver Meeting this week in Washington, DC.

    These findings have important policy implications, showing that “treatment is not only about clinical benefit but also about the patient experience,” said presenter Zobair Younossi of Inova Fairfax Hospital in Virginia.

    The advent of DAAs used in interferon-free regimens has made treatment for chronic hepatitis C shorter, better tolerated and much more effective. The latest DAAs can cure more than 90% of people with all hepatitis C virus (HCV) genotypes, usually in 8 or 12 weeks.

    Clinical trials typically focus on evaluating the safety and efficacy of new therapies. Sustained virological response, or undetectable HCV viral load at 12 weeks post-treatment (SVR12), is considered a cure. But these trials are too short to assess long-term improvements in health outcomes and quality of life, which was the aim of Younossi’s study.

    This analysis looked at people with chronic hepatitis C who achieved SVR using a sofosbuvir-based DAA regimen in trials sponsored by Gilead Sciences, and who were entered into a long-term follow-up registry that plans to follow study participants for 5 years.

    Health-related quality of life was evaluated at baseline (pre-treatment) and every 24 weeks for up to 144 weeks using Short Form-36 (SF-36). This standard measure includes eight domains: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role and mental health. These are combined into physical and mental summary scores.

    The analysis included 3486 clinical trial participants. Just over 60% were men and the mean age was 53 years. The genotype distribution was 65% genotype 1, 10% genotype 2, 18% genotype 3 and 4% genotype 4. Liver cirrhosis was present in 16% and 12% had HIV/HCV co-infection. A quarter reported depression and 16% reported anxiety at baseline.

    Compared to their health-related quality of life before starting treatment, participants saw significant improvements in all SF-36 domains. Younossi noted that the 4- to 8-point increases in scores across the various domains were not only statistically significant but also clinically relevant. The largest gains were seen in the vitality and general health domains. Increased health-related quality of life was maintained through 3 years of follow-up.

    SF-36 physical and mental summary scores began rising at the end of treatment and continued to increase after achieving SVR until they reached a plateau at around the normal levels for an age-matched general population.

    Cirrhosis, depression, anxiety and fatigue were independent predictors of lower health-related quality of life scores in a multivariate analysis. However, after adjusting for baseline levels, people with cirrhosis, depression, fatigue, insomnia and type 2 diabetes saw larger gains, suggesting that people with co-morbidities may experience the largest improvements after achieving SVR, Younossi said.

    Based on these findings, the researchers concluded, “These data support the comprehensive and sustainable benefit of HCV cure.”

    By Liz Highleyman

    Reference

    Younossi Z et al. Significant and Sustained Improvement of Health-Related Quality of Life (HRQL) Scores in Patients with Hepatitis C (HCV) and Sustained Virologic Response (SVR). The Liver Meeting, abstract 64, 2017.

    View the abstract.

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    Leading medical organizations issue recommendations regarding hepatitis C in pregnancy http://www.eatg.org/news/leading-medical-organizations-issue-recommendations-regarding-hepatitis-c-in-pregnancy/ Thu, 19 Oct 2017 21:30:58 +0000 http://www.eatg.org/?post_type=news&p=6511 High-risk pregnancy experts published eight specific recommendations for screening, treatment and management of hepatitis C in pregnancy

    Hepatitis C (HCV) during pregnancy is associated with serious, adverse outcomes. Infants born to women with HCV are more likely to experience fetal growth restriction and low birth weight. For women, chronic HCV is associated with progressive liver damage and, during pregnancy, can be transmitted from the mother to the fetus (called vertical transmission).

    Highly effective treatments for HCV now exist, but none are currently approved for use during pregnancy. Yet, up to 8% of pregnant women worldwide are infected with HCV.

    The Society for Maternal-Fetal Medicine (SMFM) today released new clinical guidance regarding HCV in pregnancy entitled, “SMFM Consult Series #43: Hepatitis C in pregnancy: screening, treatment, and management.” The recommendations are currently available on the SMFM website, will be published in the November issue American Journal of Obstetrics and Gynecology, and are endorsed by the American College of Obstetricians and Gynecologists (ACOG).

    The “SMFM Consult Series #43: Hepatitis C in pregnancy: screening, treatment, and management,” recommends that obstetric care providers should:

    • Screen women who are at increased risk for HCV at their first prenatal visit. Risk factors include the use of injected or intranasal (snorted) illegal drugs; long-term hemodialysis; women who have received a tattoo or medical procedure in an unregulated setting; being the recipient of an organ transplant or blood products; a history of incarceration; women seeking care related to other sexually transmitted infections (STIs); and chronic liver disease.

      If the initial screening results are negative, screening should be repeated later in pregnancy for women with persistent or new risk factors. HCV-positive pregnant women should be screened for other sexually transmitted infections and vaccinated for Hepatitis A and B during pregnancy.

    • Manage HCV during pregnancy, labor, and birth to decrease the risk of transmission of vertical transmission. Recommendations include: 1.) if invasive prenatal diagnostic testing is requested, women should be counseled that data on risk is limited and amniocentesis is preferred over chorionic villus sampling; 2.) HCV alone is not an indication for cesarean birth; and 3.) providers should avoid internal fetal monitoring, prolonged rupture of membranes, and episiotomy in HCV-positive women.
    • Treat HCV in the postpartum period. HCV positive women can breastfeed.

    “Not enough is known about the effect of most drugs on a woman and her pregnancy, or the ways in which pregnancy may alter the uptake, metabolism and effectiveness of medications,” said lead author and SMFM member, Brenna Hughes, MD, MSc. “The treatments currently available for HCV are no exception.”

    “More research on HCV during pregnancy is needed to further our understanding of the virus and its treatment,” said ACOG Vice President of Practice Activities, Christopher M. Zahn, MD. “With further information, obstetric care providers will be able to adequately screen for HCV and counsel pregnant women who are HCV-positive.”

    ###

    SMFM and ACOG recommend more research on HCV during pregnancy to further limit vertical transmission of the virus and to better understand the impact of HCV treatment during pregnancy. The Task Force on Research Specific to Pregnant Women and Lactating Women is beginning to address these gaps in knowledge so that obstetric care providers can counsel women about the safest possible treatment options to improve health and minimize risk.

    ACOG is participating in the National Viral Hepatitis Action Plan for 2017 – 2020 (NVHAP) to prevent/reduce viral hepatitis in the U.S., including HCV.

    For no-cost, companion patient education materials on HCV, visit SMFM’s website.

    About SMFM

    The Society for Maternal-Fetal Medicine (est. 1977) is a non-profit membership organization representing the interests of obstetricians/gynecologists who have additional formal education in maternal-fetal medicine. The Society is devoted to reducing high-risk pregnancy complications by providing continuing education to its more than 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. SMFM hosts an annual scientific meeting in which new ideas and research in the area of maternal-fetal medicine are unveiled and discussed. For more information, visit http://www.smfm.org.

    About ACOG

    The American College of Obstetricians and Gynecologists (The College), a 501(c)(3) organization, is the nation’s leading group of physicians providing health care for women. As a private, voluntary, nonprofit membership organization of more than 58,000 members, The College strongly advocates for quality health care for women, maintains the highest standards of clinical practice and continuing education of its members, promotes patient education, and increases awareness among its members and the public of the changing issues facing women’s health care. The American Congress of Obstetricians and Gynecologists (ACOG), a 501(c)(6) organization, is its companion organization. http://www.acog.org

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    Efficacy of ravidasvir plus sofosbuvir for chronic hepatitis C genotype 4 http://www.eatg.org/news/efficacy-of-ravidasvir-plus-sofosbuvir-for-chronic-hepatitis-c-genotype-4/ Thu, 19 Oct 2017 14:06:05 +0000 http://www.eatg.org/?post_type=news&p=6515 Patients with chronic hepatitis C virus-genotype-4 (HCV-GT4) in countries with limited resources may have a new treatment option with the combination of ravidasvir (an NS5A inhibitor) plus sofosbuvir, with or without ribavirin, according to a phase 3 study published in the Journal of Hepatology.

    In one of the largest studies of interferon-free direct-acting antiviral treatment conducted in patients with HCV-GT4, 300 patients were randomly assigned to one of three groups according to their previous use of interferon and whether they had cirrhosis. Two of the groups received ravidasvir 200 mg daily plus sofosbuvir 400 mg daily and were randomly assigned 1:1 to treatment with or without weight-based ribavirin for 12 weeks. The third group received ravidasvir plus sofosbuvir with ribavirin and were randomly assigned 1:1 to a treatment duration of 12 weeks or 16 weeks.

    Overall, 95.3% of patients achieved the primary end point of sustained virologic response at 12 weeks posttreatment, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, regardless of their history of interferon treatment. Concomitant treatment with ribavirin and  previous interferon use did not affect the response rates.

    Combination treatment with ravidasvir and sofosbuvir was well tolerated, and most adverse events were mild and similar to those of other direct antiviral combination therapies.

    This was the first clinical trial evaluating the combination of ravidasvir plus sofosbuvir, with or without ribavirin, and the authors concluded that “RDV plus SOF is a promising new once-daily oral treatment that was well tolerated in a large group of HCV-G4 patients, with high rates of sustained virologic response in patients with and without cirrhosis.”

    By Virginia Schad

    Reference

    Esmat G, Elbaz T, El Raziky M, et al. Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis c genotype-4 [published online September 18, 2017]. J Hepatol. doi: 10.1016/j.jhep.2017.09.006&.

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    Alnylam and Vir form strategic alliance to advance RNAi therapeutics for infectious diseases http://www.eatg.org/news/alnylam-and-vir-form-strategic-alliance-to-advance-rnai-therapeutics-for-infectious-diseases/ Wed, 18 Oct 2017 21:35:06 +0000 http://www.eatg.org/?post_type=news&p=6491 Agreement includes investigational RNAi therapeutic program for hepatitis B virus infection and discovery collaboration on additional development candidates for treatment of infectious diseases

    CAMBRIDGE, Mass., 18 October 2017 — Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced an exclusive licensing agreement with Vir Biotechnology, a company dedicated to transforming the care of people with serious infectious diseases, for the development and commercialization of RNAi therapeutics for infectious diseases, including chronic hepatitis B virus (HBV) infection. As part of this agreement, the companies will advance Alnylam’s HBV program and also initiate a research collaboration for the development and advancement of up to four additional RNAi therapeutic programs for the treatment of other infectious diseases with high unmet needs.

    “This agreement represents another step toward bringing RNAi therapeutics to patients with limited or inadequate therapeutic options. Partnering with the exceptional, experienced team at Vir to advance investigational RNAi therapeutics in infectious diseases will expedite the development path for these medicines, while enabling Alnylam to maintain operational focus on our robust pipeline of later-stage programs,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “We believe the innovative structure of this deal, including the right for Alnylam to opt into a profit-sharing arrangement prior to the start of Phase 3 for HBV, gives us both strategic flexibility in our committed spend and retention of significant product value.”

    “We are excited to partner with Alnylam to bring scientific innovation to infectious diseases, such as hepatitis B, that impact global health and currently have significant unmet needs,” said George Scangos, Ph.D., Chief Executive Officer of Vir. “This collaboration is a key step forward toward our goal of leveraging discovery and development to better control, or even cure, infectious diseases, thereby benefitting those patients most in need around the world.”

    Alnylam is developing ALN-HBV for the treatment of chronic HBV infection. A Phase 1/2 clinical trial of ALN-HBV was initiated in July 2016. Alnylam plans to discontinue further development of this investigational compound and to advance a new Development Candidate, ALN-HBV02, utilizing the Company’s Enhanced Stabilization Chemistry-Plus (ESC+) GalNAc conjugate technology. As recently reported, ESC+ conjugates have the potential to improve target specificity with an expanded therapeutic index.

    As part of the agreement, Alnylam will lead ALN-HBV02 to IND filing, with Vir then progressing ALN-HBV02 through human proof of concept (POC); the companies will co-fund the program through this point. Subsequently, Vir will fund and conduct all development through completion of Phase 2 studies. Thereafter, Alnylam retains the right to opt into a profit-sharing arrangement prior to the start of Phase 3. In connection with the companies’ research collaboration for up to four additional infectious disease programs, Vir will fund all research and development costs, while Alnylam retains a product-by-product option on each program to opt into a profit-sharing arrangement following human POC.

    Under the terms of the agreement, Alnylam will receive an upfront payment, comprised of cash and shares of Vir common stock. Alnylam is also eligible to receive more than $1 billion in potential milestone payments related to the successful advancement of ALN-HBV02 and other infectious disease programs, as well as tiered royalties on products ultimately commercialized by Vir under the collaboration, should Alnylam elect to decline its co-development and profit share option on a per-product basis.

    About HBV Infection

    Worldwide, 2 billion people – or one out of three – are infected with HBV, and more than 250 million people are chronically infected, including 1 to 2 million people in the U.S. An estimated 1 million people die each year from HBV and its complications worldwide, of whom about 5,000 are in the U.S. Worldwide, chronic infection with hepatitis causes 80 percent of all cases of hepatocellular carcinoma (HCC), which kills more than 500,000 people each year. About 5 percent of the population is a chronic carrier of HBV, and nearly 25 percent of all carriers develop serious liver diseases such as chronic hepatitis, cirrhosis or HCC. Current treatment options include long-term antiviral therapies, which permit low levels of virus cells to replicate, leading to HBV viral persistence and affecting therapeutic outcomes. There is a significant need for safe and convenient novel therapeutics that restore the host immune response through targeted hepatitis B surface antigen (HBsAg) knockdown, thereby offering HBV patients the potential for functional cures by eliminating virus-producing cells.

    About Alnylam Pharmaceuticals, Inc.

    Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, and hepatic infectious diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform and deep pipeline of investigational medicines, including four product candidates that are in late-stage development. Looking forward, Alnylam will continue to execute on its “Alnylam 2020” strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam employs over 600 people in the U.S. and Europe and is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

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    Hepatitis webinars: The entire collection from the HAND project http://www.eatg.org/news/hepatitis-webinars-the-entire-collection-from-the-hand-project/ Tue, 17 Oct 2017 21:57:05 +0000 http://www.eatg.org/?post_type=news&p=6479 In the framework of the HAND – Hepatitis Access Needs Project, EATG has produced a series of webinars about hepatitis treatment and prevention in English and Russian.

    To watch the webinars in English, click here.

    To watch the webinars in Russian, click here.

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    Restrictions on free DAA access in many European countries contrary to guidelines and undermine HCV elimination targets, say researchers http://www.eatg.org/news/restrictions-on-free-daa-access-in-many-european-countries-contrary-to-guidelines-and-undermine-hcv-elimination-targets-say-researchers/ Tue, 17 Oct 2017 21:53:42 +0000 http://www.eatg.org/?post_type=news&p=6474

    The restrictions which many European countries impose on free/reimbursed access to hepatitis C virus (HCV) direct-acting antivirals (DAAs) are contrary to guidelines and undermine the World Health Organization (WHO) goal to eliminate HCV as a major public health concern, new research suggests.

    In a study published in The Lancet Gastroenterology and Hepatology, investigators found that 46% of countries restricted free or reimbursable access to DAAs according to fibrosis stage. Approximately a fifth of countries imposed additional criteria relating to drug and alcohol abuse.

    “These restrictions are not in agreement with the 2016 European Association for the Study of the Liver (EASL) recommendations on the treatment of hepatitis C, which state that all patients without contradictions to therapy should be offered treatment,” comment the authors. “Successful treatment of HCV infection reduces progression of liver disease and decreases all-cause mortality in people with advanced liver disease. Treatment of those with the greatest risk of transmission…helps to prevent onward transmission. As such, increasing access to DAA therapy will yield both individual and public health benefits.”

    An estimated 3.2 million people in Europe have chronic HCV infection. The proportion of people with HCV-related cirrhosis and liver cancer is projected to increase by between a fifth and a third by 2030.

    All oral DAA regimens can cure HCV in almost all people. WHO has set the target of eliminating HCV as a global public health concern. For this to be achieved, it will be necessary to reduce incidence by 80%, increase diagnosis rates to 90% and to treat 80% of all diagnosed individuals. To meet these targets, it is essential that countries maximise the use of DAAs, minimising restrictions on people who are eligible for free/reimbursed access.

    Between November 2016 and August 2017, a team of investigators reviewed the criteria for free/reimbursed access to DAAs across the European Union, European Economic Area and Switzerland. They especially wanted to see if there were restrictions according to fibrosis stage, drug and alcohol use, type of healthcare provider and HCV/HIV co-infection status.

    All 35 European countries provided information.

    The most commonly prescribed free/reimbursed DAA regimen was ombitasvir, paritaprevir and ritonavir, with dasabuvir, and with or without ribavirin (94% of countries).

    Sofosbuvir and daclatasvir with or without ribavirin were the least likely to be reimbursed (63% of countries).

    Most countries provided access to sofosbuvir and ledipasvir with or without ribavirin (31 countries – 89%). Three-quarters reimbursed sofosbuvir and velpatasvir and 83% provided access to sofosbuvir with ribavirin.

    Approximately half (46%) restricted access to people with fibrosis stage F2 or higher. Moreover, five countries required a minimum of F3 and Malta demanded F4. There were no fibrosis restrictions in 13 countries (37%). Genotype and age restrictions were in place in Norway, whereas in some countries, the type of DAA regimen was dependent on fibrosis stage.

    The investigators suggest that the fibrosis restrictions are likely to be interim while countries await declines in DAA pricing. “Restrictions regarding stage of liver disease will probably be removed in many countries in the near future, as happened in Spain in June 2017,” they suggest.

    The majority of countries (89%) had no restrictions for drug and/or alcohol use. However, six (17%) demanded abstinence for six months before initiation of treatment.

    Prescribing DAAs was restricted to a specialist in 94% of countries. In England, GPs could prescribe but only with input from a local multi-disciplinary committee. Germany permitted all GPs to prescribe. In France, GPs with special training were allowed to monitor HCV once DAA therapy had been started.

    Only one country placed restrictions on the prescription of DAAs to people with HIV co-infection. In Romania, people with co-infection needed to provide evidence of a negative drug test, a restriction not placed on people with HCV mono-infection.

    “Broad access to DAAs requires negotiations to decrease DAA prices (or discounts to list prices) to facilitate removal of restrictions,” conclude the authors. “WHO mortality and incidence elimination targets are achievable and cost-effective in many countries but will require collective efforts of researchers, health-care providers, policy makers, the affected community, and the pharmaceutical industry, to succeed.”

    By Michael Carter

    Reference

    Marshall AD et al. Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe. The Lancet Gastroenterol Hepatol, online edition. http://dx.doi.org/10.1016/s2468-1253(17)30284-4 (2017)

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    Hepatitis C news http://www.eatg.org/news/hepatitis-c-news/ Tue, 17 Oct 2017 17:51:47 +0000 http://www.eatg.org/?post_type=news&p=6475
  • MedPage Today: Sustained response with HCV combo drug in CKD
  • MD Magazine: DAAs proves capable for HCV-infected heart transplant patients
  • MD Magazine: Ribavirin plasma levels predict SVR for hepatitis C infection
  • Healio: Platelet count recovers after SVR in HCV, disrupted by HBV coinfection
  • Medical Xpress: Gene transcription in virus-specific CD8 T cells differentiates chronic from resolving HCV
  • Medical Xpress: How hepatitis C hides in the body
  • Healio: US: Cost, fear of side effects key barriers to HCV treatment
  • Medscape: CDC considers expanding hepatitis C testing
  • ]]>
    Rapid fibrosis progression in large proportion of HIV-positive gay men after acute HCV http://www.eatg.org/news/rapid-fibrosis-progression-in-large-proportion-of-hiv-positive-gay-men-after-acute-hcv/ Thu, 12 Oct 2017 06:23:57 +0000 http://www.eatg.org/?post_type=news&p=6447

    Over a third of HIV-positive gay men develop significant liver fibrosis after an episode of acute hepatitis C virus (HCV) infection, German investigators report in the Journal of Viral Hepatitis. Over three years of follow-up, 39% of individuals developed fibrosis stage F2 or higher. Risk factors included older age, alcoholism and non-response to therapy based on interferon during acute infection.

    “We observed a high rate of significant liver fibrosis…and even cirrhosis (11.6%),” comment the investigators. “We interpret this finding as an effect of acute HCV on the liver, and the short HCV infection duration in this HIV-infected population was apparently sufficient to induce significant liver damage.”

    Globally, between 5 and 15% of HIV-positive people have co-infection with HCV. There are well-established epidemics of HCV among HIV-positive gay and other men who have sex with men (MSM) in Europe, Australia and the US. HCV-related liver disease is now a major cause of illness and death in people with co-infection.

    Highly effective HCV therapy using direct-acting antiviral agents (DAAs) is now available and can achieve a cure in almost all people. However, it is not currently indicated for the treatment of acute infection. Moreover, since the introduction of DAAs, the proportion of European patients with acute HCV infection opting for therapy with older interferon-based treatments has dropped dramatically, potentially increasing the risk of significant fibrosis over time.

    Rapid progression of fibrosis in men with co-infection has been reported previously in small studies in the United States and Europe. The findings published in the Journal of Viral Hepatitis represent the largest population yet studied.

    Investigators in Berlin designed a single-centre, observational study to describe rates of fibrosis progression and mortality among HIV-positive MSM with acute HCV infection. Risk factors for fibrosis progression were also analysed.

    A total of 213 cases of acute HCV were diagnosed in 178 HIV-positive MSM between 2002 and 2013. Almost a fifth (18%) of cases were re-infections. Over a third of men (38%) reported intravenous drug use during sexual encounters (“chemsex”) and 40% had a recent sexually transmitted infection, especially syphilis.

    Maximum ALT level during acute infection was a median of 421 u/l. Median HCV RNA viral load was 6.09 log10 IU/ml. The majority of cases (77%) involved HCV genotype 1a.

    A spontaneous cure was observed in 11% of individuals. This was associated with increased age, lower HCV RNA and elevated ALT levels.

    Of the men without spontaneous clearance, 86% initiated interferon-based therapy. Treatment lasted a medium of 13 weeks. At the end of therapy, a sustained virological response (SVR) – or cure – was observed in 71% of men and was associated with lower age. Individuals with physician-declared alcoholism were significantly less likely to attain SVR.

    At baseline, 90% of men had no evidence of serious liver fibrosis. But after a median of three years of follow-up, 39% had fibrosis stage F2 or higher, with 12% having cirrhosis. Older age (p = 0.02) and non-response to HCV therapy (p = 0.02) were both associated with significant fibrosis progression.

    No patient developed decompensated liver disease or liver cancer. There were ten deaths overall, (1.4 per 100 person-years). Four deaths were due to cardiovascular disease. None had liver disease as their cause.

    “With a mortality rate of 1.4/100 person-years in our cohort, rates are similar to those described in other HIV-monoinfected cohorts,” observe the investigators.

    “Older men, chronic drinkers, and those with uncontrolled HCV RNA replication are at particularly high risk of fibrosis progression,” conclude the authors. “This subgroup could warrant closer monitoring by non-invasive markers of fibrosis and should be considered for early treatment.”

    By Michael Carter

    Reference

    Steininger K et al. HIV-positive men who have sex with men are at high risk of development of significant liver fibrosis after an episode of acute hepatitis C. J Viral Hepat, 24: 832-39, 2017.

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    New fund for key populations in eastern Europe and central Asia http://www.eatg.org/news/new-fund-for-key-populations-in-eastern-europe-and-central-asia/ Tue, 10 Oct 2017 21:55:32 +0000 http://www.eatg.org/?post_type=news&p=6441

    The Elton John AIDS Foundation announced on 10 October a new funding initiative for key populations in eastern Europe and central Asia.

    The Key Populations Fund for Eastern Europe and Central Asia will focus on prevention and treatment of both HIV and hepatitis C for the people in the region most vulnerable to HIV—people who inject drugs, gay men and other men who have sex with men and sex workers. Over the next three years, the fund will aim to reach 20 000 people in the region with prevention, testing and treatment services.

    People who inject drugs, gay men and other men who have sex with men and sex workers remain disproportionately affected by HIV in eastern Europe and central Asia as they are beyond the reach of many prevention and treatment services. They make up the majority of people living with HIV in the region.

    Eastern Europe and central Asia is the only region of the world where both new HIV infections and AIDS-related deaths are rising. New HIV infections have increased by 60% and AIDS-related deaths by 38% since 2010. Only 27% of people living with HIV in the region had access to life-saving antiretroviral therapy in 2016.

    Quotes

    “This timely initiative by the Elton John AIDS Foundation focuses on the right people in the right region: key populations in eastern Europe and central Asia.”

    Vinay Saldanha, Director, UNAIDS Regional Support Team for Eastern Europe and Central Asia

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    Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users http://www.eatg.org/news/epidemic-dispersion-of-hiv-and-hcv-in-a-population-of-co-infected-romanian-injecting-drug-users/ Mon, 09 Oct 2017 21:01:14 +0000 http://www.eatg.org/?post_type=news&p=6431 Abstract

    Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population.

    Read the full study, published in PLOS ONE, here.

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    People with HIV/HCV co-infection have an increased risk of cardiovascular disease compared to people with HIV alone http://www.eatg.org/news/people-with-hivhcv-co-infection-have-an-increased-risk-of-cardiovascular-disease-compared-to-people-with-hiv-alone/ Sun, 08 Oct 2017 11:20:30 +0000 http://www.eatg.org/?post_type=news&p=6415

    People with HIV/hepatitis C virus (HCV) co-infection are between a quarter and a third more likely to develop cardiovascular disease compared to people of a similar age with HIV mono-infection, according to the results of a meta-analysis published in the Journal of Viral Hepatitis. Co-infection increased the risk of stroke by 24% and the risk of heart attack by 33%.

    “In this meta-analysis of 33,723 participants from four cohort studies, HIV/HCV coinfection was associated with a 24%-33% increased risk of CVD [cardiovascular disease] compared to HIV monoinfection,” write the investigators. ‘In coinfected individuals, it has been postulated that both viruses may act synergistically through persistent inflammatory responses to increase the risk of CVD.”

    There is a well-established link between HIV infection and CVD, with research suggesting that the risk is increased by as much as 61% compared to HIV-negative individuals. People with HCV also have an increased risk of developing CVD. It has therefore been suggested that HIV and HCV have the potential to act synergistically and increase the risk of CVD in individuals with co-infection. Studies examining whether this is the case have yielded conflicting results. To clarify this question, investigators in the United States performed a meta-analysis of studies examining the risk of CVD in adults with HIV/HCV co-infection compared to people with HIV mono-infection. Risk of CVD – coronary heart disease, congestive heart failure and stroke – was adjusted for traditional risk factors including sex, smoking, blood pressure, diabetes and LDL cholesterol.

    Four cohort studies (two prospective, two retrospective) met the inclusion criteria. A total of 33,723 were included in the analysis. The majority were men and mean age varied between 36 and 48 years. Average follow-up was between 2.3 and 7.3 years. The studies were conducted in the United States, Canada and Spain.

    Three of the four studies reported a significant association between co-infection and CVD risk. The other study also reported an increased risk, but the association was just short of significance.

    Pooled estimates indicated that co-infection increased the risk of stroke by 24% (HR = 1.24; 95% 1.07-1.40) and heart attack by 33% (HR = 1.33; 95% CI, 1.06-1.60).

    “In this meta-analysis of CVD risk among people with HIV, we found an increased risk of CVD in those with HIV/HCV coinfection compared to HIV monoinfection,” conclude the authors. “More research is needed to further quantify this association, determine potential mechanisms that underlie this association and evaluate whether treatment for HIV and HCV can reduce CVD outcomes.”

    By Michael Carter

    Reference

    Osibogun O et al. HIV/HCV coinfection and the risk of cardiovascular disease: a meta-analysis. J Viral Hepat, online edition. DOI: 10.1111/jvh.12725 (2017).

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    AASLD, IDSA update HCV guidance for resistance, new drug approvals http://www.eatg.org/news/aasld-idsa-update-hcv-guidance-for-resistance-new-drug-approvals/ Sun, 08 Oct 2017 10:35:19 +0000 http://www.eatg.org/?post_type=news&p=6412 The AASLD and the Infectious Diseases Society of America have updated their guidelines and resources for the diagnosis and treatment of hepatitis C virus infection, according to a press release.

    The updated guidelines, posted on their website HCVguidelines.org, will reflect recent FDA drug approvals of Mavyret (glecaprevir/pibrentasvir, AbbVie) and Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences), include a primer on HCV resistance, and provide direction on treating people after kidney transplantation and managing HCV in pregnant women and children, according to the release.

    “The new AASLD-IDSA Hepatitis C Guidelines are a refreshing update to one of the most useful tools on the internet for those treating hepatitis C in practice,” Michael S. Saag, MD, associate dean for global health at University of Alabama at Birmingham School of Medicine, Jim Straley Chair in AIDS research, director of the Center for AIDS Research and Co-Editor in Chief of HCV Next, said in an interview. “The tables are well designed, the information easy to access, the website is easy to navigate, and the text provides solid scientific back up to the recommendations.”

    More specifically, the HCV resistance primer will offer terminology, guidance on when to provide resistance testing and approaches to overcoming resistance, the release stated. Updated recommendations for kidney transplant patients includes how to use direct-acting antiviral (DAA) therapy in patients who have undergone kidney transplant, per the release. Additions will offer guidance on testing, treating and monitoring pregnant women and children with HCV as well as information for counseling parents, according to the release.

    “With the recent release of two novel, pangenotypic regimens, clinicians have been wondering how these new treatment options fit into existing practice,” Saag told Healio.com/Hepatology. “The updated Guidelines provide clear direction on how and when to use these newer agents, while at the same time ‘modernizing’ the regimen options from ‘yesteryear’ (literally, 1 year ago … which is a lifetime in hepatitis C drug development). All in all, a great update with accurate, well-thought out recommendations for every genotype, fibrosis stage and clinical scenario in the treatment of hepatitis C.”

    By Savannah Demko

    Disclosures: Saag reports consulting for and receiving research grants from Bristol-Meyers Squibb, Gilead, Merck, Proteus and ViiV.

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    Hepatitis C drug market: analysis http://www.eatg.org/news/hepatitis-c-drug-market-analysis/ Sun, 08 Oct 2017 10:29:17 +0000 http://www.eatg.org/?post_type=news&p=6418 Two publications in Bloomberg Gadfly and MD Magazine analyze the hepatitis C drug market.

    Access the publications here and here.

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    Viekira Pak safe for patients with HCV, Child-Pugh A cirrhosis http://www.eatg.org/news/viekira-pak-safe-for-patients-with-hcv-child-pugh-a-cirrhosis/ Sun, 08 Oct 2017 10:21:13 +0000 http://www.eatg.org/?post_type=news&p=6411 Patients with hepatitis C and Child-Pugh A cirrhosis had similar rates of treatment-related adverse events and lower rates of hepatic decompensation after treatment with Viekira Pak compared with untreated patients, according to recently published data. However, those with a history of advanced cirrhosis were more likely to experience treatment-related adverse events.

    “Importantly, many of the events consistent with hepatic decompensation were self-limiting and improved without treatment interruption, or occurred at time points not typically associated with drug toxicity,” Fred Poordad, MD, from the Texas Liver Institute and University of Texas Health Science Center, San Antonio, and colleagues wrote.

    The researchers pooled safety data from 12 phase 2 and phase 3 studies that included patients with HCV and compensated cirrhosis who received Viekira Pak (ombitasvir/paritaprevir/ritonavir, AbbVie) or ombitasvir/paritaprevir/ritonavir with dasabuvir, with or without ribavirin in either case.

    Of the 1,066 patients included in the pooled safety assessment, 846 received ribavirin and 480 were HCV treatment-naive. Patients had a baseline Child-Pugh score of five (n = 891), six (n = 130) or seven (n = 19).

    Overall, the rate of serious treatment-related adverse events was 5.3% (95% CI, 4.1-6.8) and the rate of serious treatment-related events that led to treatment discontinuation was 2.2% (95% CI, 1.4-3.2). Serious treatment-related adverse events, including those that led to treatment discontinuation, were less frequent among the 62 patients who received ombitasvir/paritaprevir/ritonavir with dasabuvir and without ribavirin.

    Thirteen patients experienced a treatment-related adverse event that the researchers considered consistent with hepatic decompensation. Eleven of those 13 received ribavirin with treatment.

    The 13 hepatic decompensation events resolved in nine patients — including six who continued treatment — were ongoing in two patients after follow-up, and led to death in one patient. One patient’s outcome was unknown.

    Compared with those who experienced a treatment-related adverse event consistent with hepatic decompensation, those who did not had a higher frequency Child-Pugh score of six or higher at baseline, platelet count of less than 90 x 109 cells/L, and serum albumin levels less than 3.5 g/dL.

    “Given that hepatic decompensation events have been reported in association with multiple classes of [direct-acting antivirals], it is unclear whether direct toxicity of DAAs, including protease inhibitors, is responsible for these events. Another possibility is that hepatic decompensation events reported with DAAs are unrelated to therapy and are instead simply part of the natural history of advanced liver disease caused by HCV infection,” the researchers wrote. “More data are needed to establish whether there is a causal relationship between this and other classes of DAA and events of hepatic decompensation.”

    Poordad F, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.06.011.

    By Talitha Bennett

    Disclosure: Poordad reports he received grants or research support from AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Genentech, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck, Novartis, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Vertex Pharmaceuticals and ZymoGenetics; is a speaker for Gilead, Kadmon, Merck, Onyx/Bayer, Genentech, GlaxoSmithKline, Salix, and Vertex; and is a consultant or advisor for AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Merck, Novartis, Tibotec/Janssen, Theravance and Vertex. Please see the full study for the other authors’ relevant financial disclosures.

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    Is HCV drug development nearing its end? http://www.eatg.org/news/is-hcv-drug-development-nearing-its-end/ Mon, 02 Oct 2017 19:57:01 +0000 http://www.eatg.org/?post_type=news&p=6364 Two new FDA approvals fill medical gaps, but access to treatment remains a challenge

    The FDA recently approved two new combination regimens for hepatitis C, raising the question of whether further drug development is warranted in this area.

    Gilead’s Vosevi (sofosbuvir/velpatasvir/voxilaprevir) and AbbVie’s Mavyret (glecaprevir/pibrentasvir) work against all hepatitis C virus (HCV) genotypes, with cure rates exceeding 95%. And Mavyret, which many patients will be able to take for just 8 weeks, brings a lower cost option to the market.

    “One could imagine something like a single injection or pill that would cure HCV, and of course that would be an advance in terms of convenience,” Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital in Boston, told MedPage Today. “But is it worth the time and resources to get that through preclinical safety studies, clinical trials, and FDA approval?”

    Experts agree, however, that more remains to be done in terms of implementation: getting everyone at risk screened for HCV infection, and getting those who test positive on effective treatment. If these goals are achieved, hepatitis C could potentially be eliminated as a public health threat.

    “The largest unmet need remains identification of cases and linkage to care of those yet to be diagnosed. For those diagnosed but not yet treated, providing access to curative therapy remains an unmet need, as many in this group still face insurance restrictions,” Raymond Chung, MD, chief of Hepatology at Massachusetts General Hospital in Boston, told MedPage Today.

    The development of direct-acting antiviral agents (DAAs) for HCV that can be used in interferon-free regimens is regarded as one of the major recent advances in medical science.

    Today’s recommended regimens are taken for 3 or 4 months, are well tolerated, and lead to sustained virological response (SVR) in more than 95% of treated patients. This represents a big improvement over the old interferon-based therapy, which lasted 6 to 12 months, caused difficult side effects, and cured only about half of treated patients.

    The approval of Vosevi and Mavyret help fill the few remaining gaps related to the effectiveness of hepatitis C treatment.

    Vosevi, approved on July 18, is a single-tablet regimen containing the HCV NS5B polymerase-inhibitor sofosbuvir (marketed separately as Sovaldi), the NS5A-inhibitor velpatasvir (currently combined with sofosbuvir in the Epclusa coformulation), and the NS3/4A protease-inhibitor voxilaprevir (approved for the first time). All of these drugs are pangenotypic, or active against all six major HCV genotypes.

    Vosevi was approved for retreatment of people with all HCV genotypes, with or without liver cirrhosis, who were not previously cured with prior DAA therapy including an NS5A inhibitor, and for those with genotypes 1a or 3 who were previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. Retreatment of these patients can be challenging because HCV can develop resistance to one medication that reduces the effectiveness of other drugs in the same class.

    In the POLARIS 1 and 4 trials, Vosevi taken for 12 weeks cured 97% of study participants with all HCV genotypes who were previously treated with DAAs, performing better than the two-drug Epclusa pill.

    For people starting treatment for the first time in the POLARIS 2 study, Vosevi taken for 8 weeks did not quite measure up to Epclusa taken for 12 weeks, with SVR rates of 95% versus 98%, respectively. The FDA therefore did not approve the shorter 8-week regimen for first-line therapy. However, Vosevi taken for either 8 or 12 weeks cured 96% of patients with HCV genotype 3 and liver cirrhosis, considered one of the most difficult groups to treat.

    Mavyret, approved on August 3, is a coformulation containing the NS3/4A protease-inhibitor glecaprevir and the NS5A-inhibitor pibrentasvir, both of which were approved for the first time.

    Mavyret was approved for previously untreated patients with HCV genotypes 1 through 6, using a treatment duration of 8 weeks for those without cirrhosis and 12 weeks for those with cirrhosis. The FDA also approved a 12- or 16-week course of Mavyret for genotype 1 patients who were previously treated with an HCV protease inhibitor or NS5A inhibitor, but not both, and for genotype 3 patients who previously used interferon-based therapy or sofosbuvir.

    In the phase III ENDURANCE AND EXPEDITION trials, Mavyret taken for 8 or 12 weeks cured 98% to 100% of patients with HCV genotypes 1, 2, 4, 5, and 6 with or without cirrhosis, and 95% of those with genotype 3 and cirrhosis. In addition, this combination taken for 12 weeks cured 98% of patients with chronic kidney disease, including those on dialysis.

    With the latest approvals, DAA development appears to be nearing its end.

    Merck, which currently markets the two-drug Zepatier (grazoprevir/elbasvir) coformulation for HCV genotypes 1 and 4, has a pangenotypic three-drug regimen containing grazoprevir, the NS5A-inhibitor ruzasvir, and the polymerase-inhibitor uprifosbuvir in late-stage development.

    Janssen recently announced that it would end its hepatitis C drug development program, after completing ongoing Phase II studies of its investigational three-drug regimen containing simeprevir (marketed alone as Olysio), odalasvir, and AL-335.

    “This decision was made in light of the increasing availability of a number of highly effective therapies addressing the medical need in hepatitis C,” the company said in a press release.

    Sax recently conducted a reader poll for the New England Journal of Medicine asking about remaining unmet needs in the hepatitis C field. Of the more than 600 respondents, 47% mentioned a vaccine to prevent HCV infection and 46% cited improved implementation to bring existing treatment to the people who need it. Fewer than 5% mentioned better options for patients with prior treatment failure, shortening the duration of therapy even further, or other improvements.

    HCV guidelines developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend that all patients with chronic HCV infection should receive treatment, except those with short life expectancies due to other causes.

    But to date, many people living with hepatitis C have been unable to access therapy because of barriers including the high cost of the drugs, refusal of coverage by private insurers or public payers, restrictions related to liver disease severity, and requirements for abstinence from drug and alcohol use. Some payers have also required that treatment be managed by liver disease specialists, even though studies have shown that primary care providers can treat hepatitis C patients with a similar rate of success.

    “Since we’re already at 98% cured with the treatments we have, and we already have salvage therapies available, I’m dubious that much more is going to be done in terms of improving DAA treatment,” Sax said. “Let’s get the people tested who are unaware of their infection so that they can get treated, and improve access once they are diagnosed. And let’s do whatever we can to stop new infections, which are occurring at a high rate among people with opiate addiction and in certain men who have sex with men.”

    The end of hepatitis C drug development does not, however, suggest that liver disease is not still an active field. Researchers continue to search for therapies to cure hepatitis B and treat fatty liver disease, which is responsible for a growing proportion of cases of hepatocellular carcinoma and liver transplantation.

    By Liz Highleyman

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    Replicor announces publication of its REP 301 study in HBV/HDV co-infection http://www.eatg.org/news/replicor-announces-publication-of-its-rep-301-study-in-hbvhdv-co-infection/ Sun, 01 Oct 2017 16:21:40 +0000 http://www.eatg.org/?post_type=news&p=6343 MONTREAL, September 28, 2017 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, announced today the publication of its REP 301 study on the activity of REP 2139 and pegylated interferon α-2a (pegIFN) in The Lancet Gastroenterology & Hepatology (http://replicor.com/science/publications/).

    The REP 301 study assessed the safety and efficacy of REP 2139 combined with pegIFN in patients with chronic HBV / HDV co-infection.  This study demonstrated several key breakthroughs in this patient population including: REP 2139-mediated HBsAg reduction to below 1IU/mL dramatically potentiates the activity of pegIFN, that profound functional control of both HBV and HDV can be established in a high proportion of patients, that this function control persists for 1 year after therapy was withdrawn and is accompanied by normalization of liver function. The critical importance of HBsAg reduction below 1IU/mL was emphasized by the lack of potentiation of pegIFN in three patients who achieved HBsAg levels as low as 16.4, 5.74 and 1.88 IU/mL during exposure to pegIFN.

    Dr. Vaillant, CSO of Replicor commented, “We are pleased to see the results of the REP 301 study published in The Lancet family of journals.  This publication demonstrates a real therapeutic advance for patients with the most aggressive form of viral hepatitis, for which there is currently no effective treatment option”, commented Dr. Andrew Vaillant, CSO of Replicor who added, “we are confident that the breakthrough results we have achieved in the REP 301 study will be significantly improved upon using the more mature REP 2139-based combination regimen currently being validated in the REP 401 protocol.”

    About Replicor

    Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.

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    8 top stories on injection drug users, HIV/HCV coinfection http://www.eatg.org/news/8-top-stories-on-injection-drug-users-hivhcv-coinfection/ Sun, 01 Oct 2017 15:00:16 +0000 http://www.eatg.org/?post_type=news&p=6353 At the recent International Symposium on Hepatitis Care in Substance Users, researchers presented new data on injection drug users and their unique risk factors for hepatitis C infection and transmission, including younger age, and the critical need for HCV education among addiction clinic workers.

    Additionally, recent news focused on the efficacy of HCV treatment in HIV/HCV coinfection, the barriers to treatment that patients with HIV/HCV face, and the fact that patients with HIV/HCV coinfection remain marginalized despite progress in screening and therapy.

    Read more here.

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    Epidemiological update: hepatitis A outbreak in the EU/EEA mostly affecting MSM http://www.eatg.org/news/epidemiological-update-hepatitis-a-outbreak-in-the-eueea-mostly-affecting-msm/ Fri, 29 Sep 2017 16:22:48 +0000 http://www.eatg.org/?post_type=news&p=6330 Since the last rapid risk assessment on this multi-country hepatitis A outbreak, 19 EU/EEA countries (Austria, Belgium, Denmark, Estonia, Finland, France, Greece, Ireland, Italy, Latvia, Luxembourg, Malta, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden and the United Kingdom-England & Wales) have reported 1 363 new outbreak-confirmed cases. Outbreak-confirmed cases are EU/EEA residents with laboratory-confirmed hepatitis A virus (HAV) genotype IA and a sequence with 99.3% homology to one of the three HAV genotype IA outbreak strains (VRD_521_2016; RIVM-HAV16-090; and V16-25801) based on overlapping fragments at the VP1-2a region.

    Read the full update here.

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    Merck discontinues MK-3682B and MK-3682C development programs http://www.eatg.org/news/merck-discontinues-mk-3682b-and-mk-3682c-development-programs/ Fri, 29 Sep 2017 16:00:04 +0000 http://www.eatg.org/?post_type=news&p=6333 Company to focus on maximizing the potential of ZEPATIER ® (elbasvir and grazoprevir)

    KENILWORTH, N.J., September 29, 2017–Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection, including ZEPATIER® (elbasvir and grazoprevir).

    “Remarkable progress has been made in the fight against hepatitis C infection, and Merck is enormously proud of the role we have had in that fight over the past 30 years,” said Dr. Eliav Barr, senior vice president, global clinical development, infectious diseases and vaccines, Merck Research Laboratories. “We will continue to study ZEPATIER to understand even more about its role in treating chronic hepatitis C infection and will continue to work with others to help bring ZEPATIER to appropriate patients with chronic hepatitis C genotype 1 or 4 infection, the genotypes which make up the majority of patients with chronic hepatitis C infection.”

    About ZEPATIER

    ZEPATIER is indicated for the treatment of chronic HCV genotype (GT) 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin in certain patient populations.

    Selected Safety Information about ZEPATIER

    The US Prescribing Information for ZEPATIER contains a Boxed Warning about the risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV. Healthcare professionals should test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating treatment with ZEPATIER. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Healthcare professionals should monitor HCV/HBV coinfected patients for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Healthcare professionals should initiate appropriate patient management for HBV infection as clinically indicated.

    HBV reactivation has been reported in HBsAg positive patients and also in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive). The risk of HBV reactivation may be increased in patients receiving some immunosuppressant or chemotherapeutic agents. HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection, reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis, ie, increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur.

    ZEPATIER (elbasvir and grazoprevir) is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). ZEPATIER is also not for use with inhibitors of organic anion transporting polypeptides 1B1/3 (OATP1B1/3) that are known or expected to significantly increase grazoprevir plasma concentrations (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort), and efavirenz. If ZEPATIER (elbasvir and grazoprevir) is administered with RBV, healthcare professionals should refer to the prescribing information for RBV as the contraindications, warnings and precautions, adverse reactions and dosing for RBV also apply to this combination regimen.

    Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Healthcare professionals should perform hepatic lab testing on patients prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.

    Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces. Healthcare providers should consider discontinuing ZEPATIER (elbasvir and grazoprevir) if ALT levels remain persistently greater than 10 times ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio.

    The concomitant use of ZEPATIER with certain drugs may lead to adverse reactions or reduced therapeutic effect due to drug interactions. Certain strong CYP3A inhibitors may increase the plasma concentration of ZEPATIER, leading to possibly clinically significant adverse reactions. Moderate CYP3A inducers may decrease the plasma concentration of ZEPATIER, leading to reduced therapeutic effect and possible development of resistance. Coadministration of ZEPATIER with these drugs is not recommended. Physicians should consult the Prescribing Information for potential drug interactions.

    In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.

    Selected Dosage and Administration Information for ZEPATIER ® (elbasvir and grazoprevir) 50 mg/100mg tablets

    ZEPATIER is a single tablet taken once daily. The recommended dosing is 12 or 16 weeks with or without RBV, depending on HCV genotype, prior treatment history and, for patients with genotype 1a infection, presence of certain baseline NS5A resistance-associated polymorphisms. See Prescribing Information for ZEPATIER for specific dosage regimens and durations. Refer to RBV prescribing information for RBV dosing and dosage modifications when ZEPATIER is given with RBV. To determine dosage regimen and duration of ZEPATIER for genotype 1a patients, testing for the presence of virus with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, or 93 is recommended prior to initiating treatment.

    About Merck

    For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

    Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

    This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

    Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

    The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2016 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

    Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir), including the Boxed Warning about the risk of HBV reactivation in patients coinfected with HCV and HBV, at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf and Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf

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    Arrowhead data reveal important considerations for future hepatitis B treatment http://www.eatg.org/news/arrowhead-data-reveal-important-considerations-for-future-hepatitis-b-treatment/ Wed, 27 Sep 2017 21:40:33 +0000 http://www.eatg.org/?post_type=news&p=6310 Results may guide new clinical approaches, Science Translational Medicine study shows

    PASADENA, Calif., Sept. 27, 2017 — Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced results from studies of ARC-520, a prior-generation RNAi therapeutic candidate against chronic hepatitis B virus (HBV) infection, in a Phase 2 clinical study in HBV patients and a complementary study in chimpanzees chronically infected with HBV. These studies demonstrated that HBV DNA integrated into the host genome is an under-appreciated source of HBV surface antigen (HBsAg), a key protein implicated in maintaining chronic HBV infection.

    In many patients, integrated HBV DNA appeared to be the dominant source of HBsAg production. The findings expand the understanding of HBV biology and host interactions, and could have important implications for future trial design and endpoint expectations for new therapies developed to cure chronic HBV. These data from study, “RNAi-based treatment of chronically infected patients and chimpanzees implicates integrated hepatitis B virus DNA as a source of HBsAg” were published in Science Translational Medicine.

    Bruce D. Given, M.D., chief operating officer and head of R&D for Arrowhead Pharmaceuticals, said: “Our experience from Arrowhead’s multiple clinical studies of our prior therapeutic candidates ARC-520 and ARC-521, and the extensive non-clinical research we completed, have provided us with invaluable insights that guide the development path of follow-on candidate ARO-HBV, a new therapy for patients with chronic HBV that utilizes the company’s next generation Targeted RNAi Molecule (TRiMTM) platform. We think long-term immune control of HBV will require reduction of HBsAg from both integrated DNA and cccDNA, which ARO-HBV is designed to do. Importantly, the findings described in the Science Translational Medicine paper extend beyond HBsAg in showing reductions in other viral antigens and viral DNA. The ARC-520 and ARC-521 data suggest that an RNAi-based approach, like ARO-HBV, could serve as a cornerstone therapy for combinations intended to cure chronic HBV because it can act as a direct anti-viral against all HBV viral products and has the potential to synergize with other agents.”

    The paper entitled, “RNAi-based treatment of chronically infected patients and chimpanzees implicates integrated hepatitis B virus DNA as a source of HBsAg,” by Christine I. Wooddell and Man-Fung Yuen et al, was made available online ahead of print in the journal Science Translational Medicine (27 September 2017).

    In the publication, several independent lines of evidence demonstrate that HBsAg is expressed not only from the episomal covalently closed circular DNA (cccDNA) minichromosome, but also from transcripts arising from HBV DNA integrated into the host genome. The latter was a large source of HBsAg production in HBeAg negative chimpanzees and presumed, by extension, in HBeAg negative and NUC experienced patients.

    “This is an important finding with wide reaching implications for the field because production of viral proteins was previously thought to depend only on transcription of viral cccDNA. We now understand that that integrated HBV DNA is a means of producing circulating HBsAg that is not dependent on viral replication, which may contribute to sustained suppression of the immune system and allow for continued virion production,” commented Christine I. Wooddell, Ph.D., lead study author. “Just a few cccDNA-containing cells able to escape immune surveillance can maintain chronic infection. Therefore, only complete immune control of HBsAg can be expected to prevent reinfection off therapy and result in a functional cure.”

    ###

    About Arrowhead Pharmaceuticals

    Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit http://www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/alerts.cfm.

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    Arbutus announces topline results for ARB-1467 Phase II Cohort 4 for the treatment of hepatitis B http://www.eatg.org/news/arbutus-announces-topline-results-for-arb-1467-phase-ii-cohort-4-for-the-treatment-of-hepatitis-b/ Wed, 27 Sep 2017 21:28:10 +0000 http://www.eatg.org/?post_type=news&p=6311 Detailed data to be presented at AASLD in October

    VANCOUVER, British Columbia and WARMINSTER, Pa., Sept. 25, 2017 — Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, announced topline results of the bi-weekly dosing segment of Cohort 4 of the Phase II study of its RNAi agent, ARB-1467.

    In the bi-weekly dosing segment of Cohort 4, twelve HBeAg negative chronically infected HBV patients on stable nucleotide therapy were given five doses of ARB-1467 on a bi-weekly dosing schedule. All twelve patients in Cohort 4 experienced reductions in serum HBsAg levels, with an average reduction in serum HBsAg of 1.4 log10, which was greater than that observed with monthly dosing in Cohorts 1-3. Seven of the twelve patients met the predefined response criteria (at least 1 log10 reduction in serum HBsAg level and a serum HBsAg level below 1000 IU/mL) at or before day 71. Five of the seven patients who met the response criteria had their serum HBsAg reduced to low absolute levels (below 50 IU/mL) during the bi-weekly dosing period. Initial results for the monthly dosing extension suggest that monthly dosing is not sufficient to maintain or improve upon these reductions in s-antigen levels. Dosing with ARB-1467 in Cohort 4 has been generally well tolerated, with no serious adverse events. Eleven of the twelve patients received all five bi-weekly doses. ALT values remained normal throughout treatment. Detailed results of Cohort 4 are expected to be presented at AASLD in October.

    “The new Phase II results for ARB-1467 show greater reduction in serum HBsAg levels with a favorable safety profile. We look forward to presenting detailed bi-weekly dosing results at AASLD,” said Dr. Mark J. Murray, Arbutus’ President and CEO. “Furthermore, we are planning to initiate a new study of ARB-1467 in 4Q17 to evaluate longer dosing of ARB-1467 combined with interferon. The design of the study is informed by the findings in Cohort 4 and has the potential to create a late stage development and possible approval pathway for ARB-1467.”

    ARB-1467 Phase 2 Trial Design

    The Phase II trial is a multi-dose study in chronic HBV patients who are also receiving stable nucleot(s)ide analog therapy. The trial consists of four cohorts, the first three of which enrolled eight subjects each (six receiving three monthly doses of ARB-1467 and two receiving placebo) and the fourth enrolled twelve patients (all of whom were to receive 5 bi-weekly doses of ARB-1467, followed by monthly dosing for patients who met predefined response criteria). Cohorts 1, 2, and 4 included HBeAg- patients and Cohort 3 included HBeAg+ patients.

    Next Steps for ARB-1467

    Arbutus will initiate a new study in 4Q17 to study longer term bi-weekly dosing of ARB-1467 in combination with tenofovir followed by the addition of pegylated interferon for patients who meet a predefined response criteria. This study will explore the effect of driving HBsAg to very low levels with ARB-1467 along with an immune modulating mechanism.

    About ARB-1467
    Arbutus’ RNAi candidate ARB-1467 comprises three RNAi triggers that target all four HBV transcripts, and has been shown in preclinical studies to reduce all viral antigen levels as well as cccDNA and HBV DNA. ARB-1467 utilizes Arbutus’ proprietary lipid nanoparticle (LNP) platform, a clinically validated delivery technology, which has been tested in hundreds of patients.

    About Arbutus

    Arbutus Biopharma Corporation is a biopharmaceutical company dedicated to discovering, developing and commercializing a cure for patients suffering from chronic HBV infection. Arbutus is headquartered in Vancouver, BC, and has facilities in Warminster, PA. For more information, visit www.arbutusbio.com.

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    Most patients with HCV genotypes 2, 4, 5, 6 achieve SVR with Mavyret http://www.eatg.org/news/most-patients-with-hcv-genotypes-2-4-5-6-achieve-svr-with-mavyret/ Wed, 27 Sep 2017 17:53:06 +0000 http://www.eatg.org/?post_type=news&p=6313 Most patients with hepatitis C genotype 2, 4, 5 or 6 who received Mavyret for 8 weeks achieved sustained virologic response with a high safety profile, according to results from three phase 3 studies. The rate of virologic failure was less than 1%.

    “A once-daily, pangenotypic regimen with shorter treatment durations for most HCV patient populations remains a high priority in the public health setting as it would simplify HCV treatment, potentially improving patient access to care and potentiating the global eradication of HCV,” Tarik Asselah, MD, PhD, from the Université Paris Diderot, AP-HP Hôpital Beaujon, France, and colleagues wrote. “Simple [direct-acting antiviral] regimens with high efficacy and tolerability, and with shorter treatment durations may improve patient adherence and reduce the burden of medical and diagnostic procedures, thereby increasing access to treatment.”

    From Oct. 1, 2014, to Oct. 25, 2016, the researchers followed patients with HCV genotype 2, 4, 5, or 6 who were treated with Mavyret (glecaprevir/pibrentasvir, AbbVie) for 8 or 12 weeks.

    In the ENDURANCE-2 study – which included 202 patients with genotype 2 – 195 of 196 treatment-naive patients achieved SVR (95% CI, 98.5-100) with no virologic failures. For the six patients with sofosbuvir-based treatment experience, the rate was 99.5% with no virologic failure.

    The ENDURANCE-4 study included 76 patients with genotype 4, 26 patients with genotype 5, and 19 patients with genotype 6. Overall, 120 of 121 patients achieved SVR (95% CI, 97.6-100) with no virologic failures.

    Of the 145 patients with genotype 2 treated for 8 weeks in the SURVEYOR-II study, 142 achieved SVR (95% CI, 94.1-99.3) and two patients had virologic failure. Five of six patients with sofosbuvir-based treatment experience achieved SVR and 135 of 137 treatment-naive patients achieved SVR (95% CI, 96.5-100). The overall SVR rate for the patients with genotype 4 (n = 46), 5 (n = 2) or 6 (n = 10) was 93% (95% CI, 83.6-97.3) with no virologic failures.

    Reasons for non-response among the three studies included the two patients with virologic relapse from the SURVEYOR-II study; missing data on one patient with genotype 2, two patients with genotype 4 and one patient with genotype 6; and one patient with genotype 2 and two patients with genotype 4 who discontinued treatment.

    The most common adverse events, which occurred in 10% or less of the study populations, included headache and fatigue. One patient discontinued treatment due to ischemic attack related to Mavyret, one discontinued due to anxiety, and one discontinued due to dyspepsia.

    “Some regimens containing HCV protease inhibitors have been associated with hepatotoxicity and gastrointestinal adverse event,” the researchers concluded. In contrast to these observations, the [Mavyret] regimen was well-tolerated, with a favorable safety profile regardless of treatment duration similar to that observed in the placebo-controlled arm. Clinically significant laboratory abnormalities, adverse events, and discontinuations due to adverse events were rare.”

    Asselah T, et al. Clin Gastroenterol Hepatol. 2017;doi:10.1016/j.cgh.2017.09.027.

    By Talitha Bennett

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    Three or more cups of coffee daily halves mortality risk in patients with both HIV, HCV http://www.eatg.org/news/three-or-more-cups-of-coffee-daily-halves-mortality-risk-in-patients-with-both-hiv-hcv/ Tue, 26 Sep 2017 19:42:47 +0000 http://www.eatg.org/?post_type=news&p=6297 Novel five-year study highlights importance of behaviors such as coffee drinking and not smoking on health and survival of HIV-infected patients, report investigators in the Journal of Hepatology.

    Patients infected by both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at specific risk of end-stage liver disease and greater risk of cardiovascular diseases and cancer. In addition, HIV infection accelerates the progression of chronic hepatitis C to fibrosis and development of cirrhosis and end-stage liver disease. In these HIV-HCV co-infected patients, drinking at least three cups of coffee each day halved the risk of all-cause mortality according to a new study published in the Journal of Hepatology.

    This study is the first to investigate the relationship between coffee consumption and the risk of all-cause mortality in HIV-HCV co-infected patients. “This is a very exciting time for HCV research as a cure that can eradicate the virus is now available for all patients,” explained lead investigator Dominique Salmon-Céron, MD, PhD, of the Service des Maladies Infectieuses et Tropicales, Hôpital Cochin, and Université Paris Descartes, Paris, France. “However, even when cured of HCV, patients co-infected with HIV have a higher risk of death with respect to the general population, due to an accelerated aging process that may result from cancer, complications related to diabetes and to liver disease, and from cardiovascular events.”

    Coffee is known to have anti-inflammatory and liver-protective properties. In the general population, drinking three or more cups of coffee a day has been found to be associated with a 14% reduction in the risk of all-cause mortality. This is probably due to the properties of polyphenols contained in coffee that can protect the liver and also reduce inflammation.

    Investigators used data from a five-year follow-up of 1,028 HIV-HCV co-infected patients enrolled in the French national ANRS CO13-HEPAVIH cohort. ANRS CO13-HEPAVIH is an ongoing French nationwide prospective cohort of HIV-HCV co-infected patients that collects both medical and psychosocial/behavioral data over time via annual self-administered questionnaires.

    At enrolment, one in four patients reported drinking at least three cups of coffee daily. Over the five years, 77 deaths occurred, almost half attributable to hepatitis C. However, the mortality risk was 80% lower in those who were cured of (i.e. who “cleared”) hepatitis C thanks to treatment.

    Further analysis showed that drinking at least three cups of coffee daily was associated with a 50% reduction in mortality risk even after taking into account HCV clearance, HIV- and HCV-related factors, and other sociobehavioral factors, such as having a steady partner and not smoking. Healthy behavior change should be promoted by physicians following HCV clearance.

    This research highlights the importance of behaviors — coffee consumption and not smoking in particular — on reduced mortality risk. These results can help promote behavioral changes in HIV-HCV patients, which in turn can result in improved survival. With respect to coffee consumption, individuals who do not drink coffee because of caffeine can still benefit from the comparable anti-inflammatory effects of decaffeinated coffee.

    First author Maria Patrizia Carrieri, PhD, of the HEPAVIH Study Group, Faculté de Médecine, Aix Marseille University, INSERM, IRD, SESSTIM, Marseilles, France, observed that coffee consumption provides more protective effects on mortality in the HIV-HCV population than in the general population.

    “The results of our study show that while curing HCV is fundamental, it must be complemented by behavioral changes if we are to improve health and survival in HIV-infected patients whether or not they cleared HCV. “I think we need to better monitor coffee consumption, together with other behaviors, such as alcohol use, smoking, physical activity, and to propose interventions to our patients which facilitate healthy behaviors even after HCV clearance. We also suggest that those patients who cannot tolerate a high intake of caffeine should consider drinking a few cups of decaffeinated coffee a day,” commented Dr. Salmon-Céron. “Accordingly, I believe that the benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in HIV-HCV patients.”

    Journal Reference:

    1. Maria Patrizia Carrieri, Camelia Protopopescu, Fabienne Marcellin, Silvia Rosellini, Linda Wittkop, Laure Esterle, David Zucman, François Raffi, Eric Rosenthal, Isabelle Poizot-Martin, Dominique Salmon-Ceron, François Dabis, Bruno Spire. Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients. Journal of Hepatology, 2017; DOI: 10.1016/j.jhep.2017.08.005
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    Interventions for reducing hepatitis C infection in people who inject drugs http://www.eatg.org/news/interventions-for-reducing-hepatitis-c-infection-in-people-who-inject-drugs/ Tue, 26 Sep 2017 19:19:26 +0000 http://www.eatg.org/?post_type=news&p=6298 The first global review to quantify the impact of needle syringe programmes (NSP) and opioid substitution treatment (OST) in reducing the risk of becoming infected with the hepatitis C virus is published in Cochrane Library Drug and Alcohol Review Group and the journal Addiction. The study, has implications for millions of people who are ‘at risk’ from infection.

    Over 70 million people live with hepatitis C and there are three to four million people newly infected each year. The main risk for becoming infected in developing countries is associated with illicit drug use and sharing used needles/syringes.  In many countries, at least half the people who have injected drugs such as heroin, cocaine or methamphetamine have hepatitis C.

    While it is known that the provision of sterile injecting equipment through NSPs or providing OST such as methadone or buprenorphine reduces injecting risk behaviour, and there is evidence also that OST and NSP reduces HIV transmission.  Until now, there has been insufficient evidence that OST and NSP can also protect against HCV infection.

    Researchers from the University of Bristol, the London School of Hygiene & Tropical Medicine, and other institutions around the world examined whether NSP and OST, provided alone or together, are effective in reducing the chances of becoming infected with hepatitis C in people who inject drugs.

    The team identified 28 research studies across Europe, Australia, North America and China. On average across the studies, the rate of new hepatitis C infections per year was 19.0 for every 100 people. Data from 11,070 people who inject drugs who were not infected with hepatitis C at the start of the study were combined in the analysis. Of the sample, 32 per cent were female, 50 per cent injected opioids, 51 per cent injected daily, and 40 per cent had been homeless.

    There was consistent and strong evidence that current use of OST (defined as use at the time of survey or within the previous six months) reduces risk of hepatitis C infection by 50 per cent and when combined with high coverage NSP reduces risk by 74 per cent.  However, there was more uncertainty on the effectiveness of NSP alone.  Studies in Europe which tended to measure high coverage in terms of the people who receive 100 per cent sterile syringes per injection showed more than 50 per cent reduction in HCV, but studies in North America which often measured coverage in terms of frequency of NSP attendance showed little effect.  There were no randomised controlled trials (RCT) of either OST or NSP on HCV.

    Dr Lucy Platt, lead author and Associate Professor in Public Health Epidemiology from the London School of Hygiene & Tropical Medicine, said: “This is the first global systematic review of quantitative studies on the effectiveness of OST and NSP on reducing Hepatitis C. Our findings provide strong evidence that OST especially in combination with high coverage of NSP can reduce HCV transmission. Up to half of people who inject drugs have hepatitis C: there is an urgent need to scale up these interventions to prevent on-going transmission, unnecessary deaths and illness.”

    Matthew Hickman, author and Professor in Public Health and Epidemiology and Head of Population Health Sciences at the University of Bristol, added:”Globally access to OST and NSP is poor and in some countries (such as Russian Federation) OST is unavailable.  Our evidence underpins European and global recommendations that OST and NSP should be expanded to prevent transmission of Hepatitis C.

    “Policies that make the cessation of injecting a requirement to qualify for OST and prevent the distribution of needles/syringe while using OST need to be removed to maximise reduction in HCV transmission. Scaling up OST and NSP is an essential part of comprehensive strategies to prevent HCV transmission and disease.

    “It is important also that the evidence base is strengthened. RCT are no longer ethical – so better observational studies are needed with consistent measures of NSP and OST as part of the scaling up of these interventions or PWID.”

    The study was funded by the National Institute for Health Research’s (NIHR) Public Health Research Programme, the Health Protection Research Unit in Evaluation of Interventions, and the European Commission Drug Prevention and Information Programme (DIPP), Treatment as Prevention in Europe: Model Projections.

    Papers:

    Needle syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis’ by Lucy Platt et al in Addiction [open access]

    Interventions for reducing hepatitis C infection in people who inject drugs’ by Lucy Platt et al in Cochrane

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    All Swiss hepatitis C patients can access costly drugs like Harvoni http://www.eatg.org/news/all-swiss-hepatitis-c-sufferers-can-access-costly-drugs-like-harvoni/ Wed, 20 Sep 2017 21:55:51 +0000 http://www.eatg.org/?post_type=news&p=6246 All patients suffering from hepatitis C can be treated with the drugs Harvoni and Epclusa from next month, after the Federal Office of Public Health lifted restrictions allowing the medicines to be reimbursed by mandatory health insurance.

    The two drugs will be available to all patients irrespective of the level and stage of infection, the office said in a statement on Tuesday. The brand-name drugs (sold as Harvoni or Epclusa) manufactured by American pharmaceutical Gilead costs between CHF33,000 to CHF60,000 ($34,048 to $61,713) for the 8-12-week therapy.

    The decision follows a softening of the government’s stance. Earlier these drugs were only available to those with an advanced form the disease. Others – around half of all sufferers – were forced to buy cheap generics from countries like India, often through buyer’s clubs.

    In April, plans were announced to make it easier for high-risk patients like drug addicts, as well as HIV and Hepatitis B sufferers, to access the two drugs even if the disease is only in an intermediary stage.

    From July 1, the health office made Zepatier, produced by pharma company Merck Sharp & Dohme, available to all patients from after also allowing it to be reimbursed by mandatory insurance. The 12-week treatment costs CHF31,000 ($31,952) per patient and was previously only available to those with an advanced form of the disease.  The same occurred for the drug combination Viekirax/Exviera from September 1. These two treatments are taken by 63% of patients.

    Hepatitis C affects between 50,000 to 80,000 Swiss residents, or 0.7% of the population, compared to 3% worldwide. The number of new Swiss cases has been stable since 2006.

    Price point 

    The recent changes result from negotiations between the health office and the biopharmaceutical company Gilead Sciences Inc, which accepted sizeable price reductions of Harvoni and Epclusa, the health office declared.

    The Swiss health office expects to have to cover additional costs only for a limited period, despite an expected doubling of the number of treatments.

    The unrestricted reimbursement of new hepatitis C drugs by Swiss mandatory health insurance is in line with international health directives, which recommend full access to such medicines as soon as it becomes economically viable.

    Only specialist doctors will be able to prescribe the new drugs to patients and decide when they are needed. The new measure is limited to an initial two-year period, subject to verification.

    Hepatitis C is an inflammation of the liver that occurs due to an infection by the Hepatitis C virus. It is transmitted via the blood of a person with disease, usually through shared syringes or insufficiently sterlised medical or tattoo instruments. Rarely, it is transmitted through sexual intercourse or from mother to child. Symptoms include fatigue, loss of appetite, nausea, vomiting, joint pains and jaundice.

    However, around 75% of those infected show no symptoms at all and are thus unaware they have the disease. For the majority (70-80%), it develops into a chronic infection and remains in the liver. After several decades, some (5-30%) develop liver scarring or cirrhosis and are more likely to get liver cancer. Chronic Hepatitis C sufferers constitute the largest demand for liver transplants. Most diagnosed infections can be traced back to intravenous drug use but transmission among men who have sex with men is on the rise.

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    Does drug injection equipment other than syringes transmit hepatitis C? http://www.eatg.org/news/does-drug-injection-equipment-other-than-syringes-transmit-hepatitis-c/ Wed, 20 Sep 2017 18:42:18 +0000 http://www.eatg.org/?post_type=news&p=6245

    Sharing drug preparation paraphernalia may not significantly contribute to hepatitis C virus (HCV) transmission among people who inject drugs, according to a study recently published in The Journal of Infectious Diseases.

    In an experiment designed to mimic real-world injection practices, the researchers were unable to detect HCV in cookers, and seldom able to do so in filters, after these items were exposed to the contents of syringes known to be contaminated with the virus.

    Needle exchange and distribution programmes that provide sterile syringes have been credited with substantially reducing transmission of blood-borne diseases including HIV, hepatitis B and hepatitis C among people who inject drugs.

    These viruses – especially HCV, which is able to live outside the body longer than HIV – can potentially be transmitted through any item that comes into contact with blood. Most harm reduction programmes therefore offer drug preparation equipment such as cookers (bottle caps or other small receptacles used to mix drugs), filters (cotton or other material used to strain a drug solution) and clean water, in addition to syringes.

    Robert Heimer of Yale University School of Public Health and colleagues conducted a study to look for HCV in drug preparation paraphernalia under conditions similar to those that occur when people share drugs.

    Previous studies by Heimer and others have suggested that cookers and filters can transmit HCV. However, it is unclear if HCV infections linked to sharing paraphernalia reflect contamination of the paraphernalia itself, or if the virus spreads through syringes when drugs are shared, the authors noted as background.

    The researchers designed laboratory experiments to replicate real-world injection practices among people who share drugs. Often people will jointly obtain a bag of heroin, for example, which one individual mixes in his or her syringe, and the solution is then portioned out to the others. Older and more experienced users – who have had more opportunities to acquire HCV – may be more likely to do this drug preparation.

    The residual contents of ‘input’ syringes known to be contaminated with HCV were passed through cookers and filters and transferred into a second ‘receptive’ syringe. The study tested syringes with detachable needles and those with fixed needles (e.g. disposable insulin syringes). All items were then tested for the presence of infectious HCV.

    HCV could not be recovered from cookers, regardless of cooker design or the type of syringe used, according to the report. The virus was only detected in input syringes with detachable needles, not those with fixed needles (73.8 vs 0% detection).

    HCV was seldom found in filters, but this happened more often when detachable needles were used compared with fixed needles (15.4 vs 1.4% detection). Finally, HCV was about twice as likely to be detected in the receptive syringe if the input syringe had a detachable instead of a fixed needle (93.8 vs 45.7% detection).

    These results are “consistent with the hypothesis that sharing paraphernalia does not directly result in HCV transmission, but is a surrogate for transmissions resulting from sharing drugs,” the study authors concluded. They suggested that this kind of sharing “is a surrogate for situations in which HCV-discordant injectors share drugs,” meaning one individual is HCV-positive and the other HCV-negative.

    The findings, they added, have implications for HCV prevention efforts and programmes that provide education and safe injection supplies for people who inject drugs.

    Heimer’s team suggested that in light of these results, syringe access programmes should not spend their limited funds on cookers and filters, but should instead focus their efforts on distributing more syringes with fixed needles.

    “At a minimum, our findings should compel programs that serve [people who inject drugs] to focus more on the process of drug preparation and injection and less on the preparation paraphernalia,” they wrote. “Going further, programs may want to reconsider expending scarce resources to provide supplies that will do little or nothing to prevent HCV transmission.”

    Some harm reduction advocates, however, take issue with this conclusion. Beyond HCV transmission, providing clean cookers and filters can also help prevent bacterial infections and ‘cotton fever’. And these supplies are inexpensive, so omitting them would not free up much money.

    “We are in the midst of a syringe exchange funding crisis, as a surge in demand (more people who inject drugs) plus a tremendous growth in new programs has dramatically outpaced availability of public and private funds,” said Daniel Raymond of the Harm Reduction Coalition. “However, any discussions or decisions about scaling back on purchasing or provision of cookers, etc, should be driven by people who inject drugs and program participants, who may place values on these supplies independent of their utility in HCV prevention.”

    By Liz Highleyman

    Reference

    Heimer R et al. Recovery of infectious hepatitis C virus from injection paraphernalia: implications for prevention programs serving people who inject drugs. Journal of Infectious Diseases, 2017.

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    In HBV, high core-related antigen levels predict cirrhosis http://www.eatg.org/news/in-hbv-high-core-related-antigen-levels-predict-cirrhosis/ Wed, 20 Sep 2017 18:18:32 +0000 http://www.eatg.org/?post_type=news&p=6256 Elevated hepatitis B virus core-related antigen levels significantly increased the risk for progression to cirrhosis among patients with chronic hepatitis B who are hepatitis B e antigen-negative and are not receiving nucleos(t)ide analogue therapy, according to recently published data.

    “Recently, various indices of liver fibrosis based on clinical and biological data have been reported to be useful predictors of fibrosis in liver disease,” Toshifumi Tada, MD, from the Ogaki Municipal Hospital, Japan, and colleagues wrote. “Our findings suggest that an elevated HBcrAg level should be considered a new criterion for starting antiviral therapy in order to decrease the risk of cirrhosis in HBV carriers.”

    From 1991 to 2014, the researchers enrolled 529 hepatitis B surface antigen-positive patients in their hepatocellular carcinoma surveillance program. Patients were HBeAg-negative, not receiving nucleos(t)ide analogue (NA) therapy, had no evidence of hepatitis C coinfection, no other cause of chronic liver disease, and a FIB-4 index score of 3.6 or lower.

    During a median follow-up of 10.9 years (range, 6-17.6 years), 84 patients progressed to cirrhosis or a FIB-4 index score higher than 3.6. The cumulative progression rates were 6.6% at 5 years, 12.3% at 10 years, 17.3% at 15 years, and 26.2% at 20 years.

    HBcrAg level was the most significant marker for progression to cirrhosis (P < .001), followed by HBsAg level (P = .009), HBV DNA level (P = .025), precore status (P = .039) and basal core promoter status (BCP; P = .044).

    After adjusting for HBV genotype, HBsAg levels, HBV DNA levels, HBcrAg levels, precore status and BCP status, HBcrAg levels of 3.7 log U/mL or higher (HR = 3.28; 95% CI, 1.6-6.75) and HBsAg levels of 3 log U/mL or higher (HR = 0.53; 95% CI, 0.3-0.94) remained independently associated with progression to cirrhosis.

    “NA therapy was reported not only to prevent the progression of hepatitis, but also to reduce the risk of HCC,” the researchers wrote. “Therefore, NA therapy is recommended for HBeAg seroconverters with elevated HBcrAg levels, even if they have low [alanine aminotransferase] and HBV DNA levels.”

    Tada T, et al. J Gastroenterol Hepatol. 2017;doi:10.1111/jgh.13989.

    By Talitha Bennett

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    Hepatitis D virus in Africa: several unmet needs http://www.eatg.org/news/hepatitis-d-virus-in-africa-several-unmet-needs/ Wed, 20 Sep 2017 18:16:48 +0000 http://www.eatg.org/?post_type=news&p=6242 A systematic review and meta-analysis, published in The Lancet Global Health, assessed anti-hepatitis D virus seroprevalence in HBsAg-positive patients in sub-Saharan Africa.

    The full analysis can be assessed here.

    An accompanying comment can be assessed here.

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    Study shows DAAs are not associated with increased HCC recurrence risk http://www.eatg.org/news/study-shows-daas-are-not-associated-with-increased-hcc-recurrence-risk/ Mon, 18 Sep 2017 16:42:05 +0000 http://www.eatg.org/?post_type=news&p=6240 Direct acting antivirals (DAA) are a novel and completely oral hepatitis C therapy that is associated with a high response rate. DAAs are used in most patients being treated for hepatitis C, including those with decompensated cirrhosis.

    This type of treatment has now completely replaced interferon-based therapy for patients with hepatitis C, a therapy which was also associated with a decrease in hepatocellular carcinoma (HCC) incidence in 40% to 50% of patients.

    Initially, it was thought that DAAs would also decrease HCC recurrence, but a multicenter, single-arm, retrospective study out of Spain demonstrated an increase in the early recurrence of HCC following treatment with DAAs. Among 58 patients with a history of HCC and a complete response early recurrence was observed in 16 patients (27.6%) when treated with DAA.

    “There have been several subsequent studies that show conflicting results in terms of this question,” said Amit G. Singal, MD. “Some studies show a high recurrence rate, and some show a relatively low recurrence rate.”

    In his presentation during the 2017 International Liver Cancer Association Annual Conference, Singal addressed this fear that healthcare providers now have of DAAs.1

    Singal noted that many of these conflicting studies have had limitations, such as small sample size, short duration of follow-up, and lack of comparator arm. For example, in a study by Dr Tatsuya Minami et al, of 27 patients, the recurrence rate at 2 years was 29.8%,2 while in a study by Pol, et al, there was only a 9.0% recurrence rate with 189 patients evaluated.3

    “As you can imagine, this created fear that there may be unintended effects from treatment with the DAAs and selecting groups of patients,” said Singal.

    In a study evaluating the association between DAA therapy and HCC recurrence among patients with HCC who achieved a complete response (CR), Singal aimed to clear up conflicting data surrounding DAAs.

    The multicenter, cohort study in the United States included adult patients with hepatitis C-related HCC with CR per modified RECIST criteria after resection, local ablative therapies, transarterial chemoembolization, stereotactic body radiation therapy, or transarterial radioembolization from January 2013 to December 2016. The primary endpoints were proportion of patients with HCC recurrence and time to recurrence.

    In the treatment arm, patients eligible were treated with DAA for any period of time (n = 207). The control arm included only patients with HCC CR and no DAA exposure (n = 127). The median age for the DAA-treated group was 63 years (72%) versus 61 years (81%) for the DAA-naïve patients. Of the DAA-treated patients, 180 (87%) were early stage via Milan criteria, and 103 (83%) were early stage in the DAA-naïve group.

    Median follow-up was 24.1 (17.0-32.4) months for the DAA-treated populations, and 15.9 (9.2-23.0) months for the DAA-naïve patients (P <.001).

    An interim analysis at a median 20.7-month follow-up showed that HCC recurrence was not higher in patients treated with DAAs; recurrence overall was observed in 47.6% of patients. Recurrence was observed in 95 patients treated with DAAs (45.9%) versus 64 DAA-naïve patients (P = .42). Also, early recurrence was not higher in patients treated with DAA, with 15 patients with DAA showing early recurrence (7.3%) versus 14 (11.0%) in DAA-naïve patients (P = 0.23).

    “We found DAAs did not have an association with increased recurrence, and the recurrence rates between the 2 groups were similar,” said Singal. “If anything, the time to recurrence was longer in the DAA-treated group than the untreated group.”

    Therapy with DAAs was associated with longer time to HCC recurrence, with the median time-to-recurrence in the DAA-treated patients at 13.4 months versus 8.0 months in the DAA-naïve patients (P <.001).

    These results summarize the safety of DAAs in regard to HCC recurrence. Additionally, patients who are not treated with DAAs may have lower rates of treatment eligibility and response rates, he noted.

    “Further studies with longer follow-up and careful evaluation for HCC recurrence are still needed. However, the hope is that this will offer some reassurance to providers that DAAs are likely safe in these patients who had HCC and had a complete response and that they can be used to cure the hepatitis C in these patients.”

    By Angelica Welch

    References

    1. Singal AG, Hoteit M, John BV, et al. Direct acting antiviral therapy is associated with shorter time to HCC recurrence but not increased risk of recurrence. In: Proceedings from the 2017 International Liver Cancer Association Annual Conference; September 15-17, 2017; Seoul, South Korea. Abstract 0-021.
    2. Minami T, Tateishi R, Nakagomi R, et al. The impact of direct-acting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma. J Hepatol. 2016;65(6):1272-1273. doi: 10.1016/j.jhep.2016.07.043.
    3. The ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT cohorts). Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J Hepatol. 2016;65(4):734-40. doi: 10.1016/j.jhep.2016.05.045.
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    HCV drug resistance: infrequent, and frequently overcame http://www.eatg.org/news/hcv-drug-resistance-infrequent-and-frequently-overcame/ Mon, 18 Sep 2017 16:38:08 +0000 http://www.eatg.org/?post_type=news&p=6239 Hepatitis C virus (HCV) mutations that can resist drug treatment are infrequent, and are unlikely to withstand longer treatment durations or the addition of a synergistic drug, according to new analysis of resistance testing, treatment response and re-treatment interventions.

    David Wyles, MD, University of Colorado, and Anne Leutkemeyer, MD, University of California San Francisco, found that resistance-associated substitutions (RASs) occur in all HCV proteins but few impact treatment outcomes, and testing for viral resistance is unnecessary to successfully treat the majority of patients with HCV infection.

    The data revealed that RASs are principally measured in genotype 1 and, to a lesser extent, genotype 3 infection. Exposure to NS5A inhibitor direct acting antivirals (DAAs) promotes emergence of the RAS S282T in genotype 1, but its modest level of drug resistance in-vitro has not become clinically significant.

    “Clinically, S282T has not been shown to impact the efficacy of sofosbuvir (Solvaldi),” researchers wrote in the study. “Thus, there is no current role for NS5B resistance testing in treatment-naïve or experienced individuals.”

    “NS5A resistance persists for months to years,” Luetkemeyer told MD Magazine.  “It may occur in the absence of prior treatment, and is relative, in that the impact of RAS can be overcome in many cases with increased duration or the addition of ribavirin.”

    The next generation of NS5A inhibitors, pibrentasvir (ABT-530) and ruzasvir (MK-8408), appear to exert activity against all the key single-position NS5A RASs in genotypes 1a and 1b. Wyles and Luetkemeyer anticipate that these will prove effective despite emergence of RAS to the current NS5A products.

    Resistance testing does appear to Wyles and Luetkemeyer to be indicated, however, in patients with genotype 1a before treatment with elbasvir/grazoprevir (Zepatier, Merck), and should be considered prior to treatment with ledipasvir/sofosbuvir (Harvoni) for those with genotype 1a and cirrhosis or with prior NS5A treatment failure.

    These patients should be tested prior to treatment, Luetkemeyer said, “as presence of NS5A RAS will impact the length of therapy and the need for ribavirin.”

    For patients demonstrating RAS prior to elbasvir/grzoprevir, Wyles and Luetkemyer found clinical trial evidence that extending treatment from 12 weeks to 16 weeks is associated with sustained virologic response (SVR) in 100% of patients. For those receiving ledipasvir/sofosbuvir, an extension to 24 weeks or adding ribavirin achieved that virtual cure.

    There are less data available to guide RAS testing for patients with the more difficult-to-cure genotype 3 HCV, although the most prominent NS5A RAS in genotype 3 has been identified as Y93H. Wyles and Luetkemeyer found sufficient trial evidence to recommend baseline testing for Y93H, with probable extension of treatment or addition of ribavirin in select populations receiving daclatasvir (Daklinza, Bristol-Myers Squibb) plus sofosbuvir or sofosbuvir/velpatasvir (Epclusa).

    Failure to respond to an initial DAA regimen is another indication for resistance testing, given the high rate of emergence and persistence of RASs in that population,” researchers wrote. “NS5A testing is recommended at the time of failure of NS5A inhibitor-based treatment and still may be useful months to years afterward.”

    The exception, Luetkemeyer commented, may be with new multiclass combination regimens for re-treatment.

    “New salvage regimens such as Vosevi (sofosbuvir/velpatasvir/voxilaprevir) may obviate the need for NS5A resistance testing in prior NS5A treatment failures,” she said.

    The study, “Understanding Hepatitis C Virus Drug Resistance: Clinical Implications for Current and Future Regimens,” was published online in Topics in Antiviral Medicine.

    By Kenneth Bender

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