Hepatitis | EATG http://www.eatg.org European AIDS Treatment Group Thu, 16 Nov 2017 19:34:07 +0000 en-US hourly 1 https://wordpress.org/?v=4.8 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.

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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.

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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%).

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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
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    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.”

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    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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    Malaysia issues compulsory license for Gilead hepatitis C drug http://www.eatg.org/news/malaysia-issues-compulsory-license-for-gilead-hepatitis-c-drug/ Sat, 16 Sep 2017 19:40:08 +0000 http://www.eatg.org/?post_type=news&p=6224 Late last month, Malaysia’s government issued a compulsory license in an effort to offer a less-expensive version of Gilead’s hepatitis C drug and increase access.

    Reports of the government move in Malaysia coincided with Gilead’s decision on 24 August to extend its voluntary licenses on its hepatitis C medicines to include Malaysia, Ukraine and Belarus.

    Previously, the company signed agreements with 11 India-based manufacturers to make generics of its hepatitis C medicines for 91 developing countries.

    Compulsory License

    One of the reasons countries can be hesitant to issue compulsory licenses is that they can be put on a US watch list that points out countries that “deny adequate and effective protection of intellectual property rights,” or that “deny fair and equitable market access to United States persons that rely upon intellectual property protection,” though the issuance of compulsory licenses is permissible under international law.

    And the case for issuing a compulsory license in Malaysia (a move the country has also made previously to increase access to generic HIV drugs more than a decade ago) was made in a recent report that discussed the impact of that first issuance.

    The report says this first compulsory license and the subsequent importation of generic HIV medicines reduced the average cost of treatment per month per patient from USD $315 to USD $58, and government treatment capacity increased from 1,500 to 4,000 patients.

    “While the Malaysian government has been offered the price of USD $12,000 [for Gilead’s sofosbuvir or Sovaldi], bioequivalent generics are available for much less i.e. USD $200-1000, and this means that patients will not be able to access these generics until the expiry of the monopolies,” the report contended.

    The report also highlighted Ukraine’s challenges and legal battles with Gilead over the intellectual property of sofosbuvir.

    Meanwhile, some are saying Gilead only decided to include Malaysia in its voluntary license program because the government issued a compulsory license.

    In an op-ed in Malaysia’s Star published Monday, Martin Khor, executive director of the intergovernmental organization known as the South Centre, said the government’s decision to issue a compulsory license “is believed to be the main reason why the firm is now including Malaysia” in its licensing deal, though it remains to be seen if the compulsory license will stand or if Malaysia will work with Gilead.

    Report: At the edge of a miracle: The hepatitis C virus (HCV) epidemic in Malaysia

    By Zachary Brennan

     

    See also:

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    Two approvals offer even more options for HCV treatment http://www.eatg.org/news/two-approvals-offer-even-more-options-for-hcv-treatment/ Sat, 16 Sep 2017 10:23:15 +0000 http://www.eatg.org/?post_type=news&p=6227 The approval of two new regimens for treating hepatitis C comes as a very welcome development in the field. It is great news for patients and providers because both regimens offer new options for therapy.

    Read the full article here.

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    US: HIV/HCV coinfection remains marginalized despite progress http://www.eatg.org/news/us-hivhcv-coinfection-remains-marginalized-despite-progress/ Sat, 16 Sep 2017 10:22:30 +0000 http://www.eatg.org/?post_type=news&p=6226 The population of patients coinfected with HIV and hepatitis C in the U.S. remains largely marginalized for one reason or another. They are opioid drug users, Medicaid recipients, men who have sex with men; often, they are all the above. The fact that there are medications in the marketplace that can control or cure their dual infections makes their predicament even more frustrating. These are people who, clinically speaking, should be leading normal, healthy lives. Yet they are not.

    Read the full article here.

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    Hepatitis care in substance users http://www.eatg.org/news/news-from-the-6th-international-symposium-on-hepatitis-care-in-substance-users/ Sat, 16 Sep 2017 10:20:21 +0000 http://www.eatg.org/?post_type=news&p=6201 News from the 6th International Symposium on Hepatitis Care in Substance Users
    6 – 8 September 2017
    Jersey City/New York, United States

     

    Other news:

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    Future complications of chronic hepatitis C in a low-risk area: projections from the hepatitis C study in Northern Norway http://www.eatg.org/news/future-complications-of-chronic-hepatitis-c-in-a-low-risk-area-projections-from-the-hepatitis-c-study-in-northern-norway/ Sat, 16 Sep 2017 10:11:23 +0000 http://www.eatg.org/?post_type=news&p=6223 Abstract

    Background

    Hepatitis C (HCV) infection causes an asymptomatic chronic hepatitis in most affected individuals, which often remains undetected until cirrhosis and cirrhosis-related complications occur. Screening of high-risk subjects in Northern Norway has revealed a relatively low prevalence in the general population (0.24%). Despite this, late complications of HCV infection are increasing. Our object was to estimate the future prevalence and complications of chronic HCV infection in the period 2013–2050 in a low-risk area.

    Methods

    We have entered available data into a prognostic Markov model to project future complications to HCV infection.

    Results

    The model extrapolates the prevalence in the present cohort of HCV-infected individuals, and assumes a stable low incidence in the projection period. We predict an almost three-fold increase in the incidence of cirrhosis (68 per 100,000), of decompensated cirrhosis (21 per 100,000) and of hepatocellular carcinoma (4 per 100,000) by 2050, as well as a six-fold increase in the cumulated number of deaths from HCV-related liver disease (170 per 100,000 inhabitants). All estimates are made assuming an unchanged treatment coverage of approximately 15%. The estimated numbers can be reduced by approximately 50% for cirrhosis, and by approximately one third for the other endpoints if treatment coverage is raised to 50%.

    Conclusion

    These projections from a low-prevalence area indicate a substantial rise in HCV-related morbidity and mortality in the coming years. The global HCV epidemic is of great concern and increased treatment coverage is necessary to reduce the burden of the disease.

    Read the full study here.

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    Study finds no significant correlation between psoriasis and prevalence of HBV and HCV http://www.eatg.org/news/study-finds-no-significant-correlation-between-psoriasis-and-prevalence-of-hbv-and-hcv/ Sat, 16 Sep 2017 10:10:45 +0000 http://www.eatg.org/?post_type=news&p=6205 Psoriasis is a poorly understood skin disorder and auto-immune disease characterized by rapidly dividing skin cells that reach the surface of the skin, eventually leading to red plaques and scales. In the United States, 2% of the population is thought to be affected with psoriasis. Although very little is known about the causes of the disorder, previous work has shown an association between psoriasis and hepatitis B and C. Hepatitis C is caused by the hepatitis C virus (HCV) and chronically affects 71 million people worldwide. Hepatitis B, on the other hand, is caused by the hepatitis B virus (HBV) and it is estimated that 257 million people have HBV.

    There have been contradictory reports about the relationship between psoriasis and hepatitis, leading researchers at the Department of Dermatology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois to assess the prevalence of psoriasis in patients infected with HCV or HBV. The cross-sectional, single-center study, led by principal investigator Beatrice Nardone, MD, PhD, was recently published in the Journal of the American Academy of Dermatology.

    The authors utilized the Northwestern Medicine Enterprise Data Warehouse (NMEDW), a large electronic medical database with information on more than 4 million patients. They searched the database for patients between the ages of 18 and 89 who were screened for either HBV or HCV between September 2010 and September 2016. This group was then divided into those diagnosed with psoriasis and those unaffected with the disease.

    The study consisted of 114,855 patients that were screened utilizing a serology-based test for HBV or HCV. The majority of patients were from the Chicago metropolitan area, with a small group of patients originating from rural areas. Out of the total 114,855 included in the study, 2,590 patients were diagnosed with psoriasis.

    After utilizing logistic regression analysis, the authors found that there was no significant difference between patient groups that were diagnosed with psoriasis and those that were not in terms of HCV or HBV prevalence.

    Of note is the fact that the authors did not account for the presence of additional risk factors for HCV and HBV, which is a major limitation of this work. Additional limitations of the study are the limited demographic utilized, with the majority of patients coming from an urban, midwestern United States population which is not indicative or representative of the general US population. In addition, the authors had no way to assess patients that were diagnosed with psoriasis but were not screened for HBV or HCV. On the other hand, strengths of this study include its large sample size, good gender representation, as well as serology-based screening and diagnosis for chronic HCV and HBV.

    Overall, the authors concluded that there is no statistically significant correlation between being infected with chronic HBV or HCV and having psoriasis. This work is significant as it shed light on a previously reported correlation that had been poorly explored in the literature. Larger, multicenter studies using a larger demographic are needed to truly determine any correlation.

    By Samar Mahmoud

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    High prices of DAAs mean there’s been little progress towards achieving WHO target of eliminating HCV by 2030 http://www.eatg.org/news/high-prices-of-daas-mean-theres-been-little-progress-towards-achieving-who-target-of-eliminating-hcv-by-2030/ Wed, 13 Sep 2017 21:50:12 +0000 http://www.eatg.org/?post_type=news&p=6187

    Only a handful of countries are on course to achieve the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) as a major public health concern by 2030, according to a study published in the Journal of Virus Eradication.  Investigators estimated progress towards elimination by examining 2016 data on rates of cure after therapy with direct-acting agents, HCV-related deaths and new HCV infections. An overall reduction in prevalence of 0.71% was observed in the 91 countries included in the study, and global prevalence fell by just 0.4%.

    “Some countries are treating a high percentage of patients, with significant reductions in HCV epidemic size,” comment the authors. “By contrast other countries have very low rates of treatment, and new HCV infections are driving the HCV epidemics.”

    Cure rates considerably outpaced the rate of new infections in North America and North Africa/Middle East. But the opposite was true in sub-Saharan Africa and Central and Eastern Europe.

    More needs to be done to expand access to affordable HCV therapy, improve HCV detection and prevention and to strengthen health systems to deliver treatment, suggest the authors.

    In 2016, WHO set the target of treating 80% of patients with HCV by 2030 to reduce the rate of new infections by 90% in that year. If achieved, this would eliminate HCV as a major public health concern.

    This is potentially achievable as treatment with DAAs can cure at least 90% of patients. It has already been shown that increasing treatment rates can lead to lower infection rates. The Netherlands provided unrestricted access to DAAs for all patients newly infected with HCV in 2015, leading to a 51% fall in new infections among men who have sex with men, the first reduction in HCV infections seen in this population for over a decade.

    To estimate global progress towards the attainment of the WHO 2030 target, investigators examined 2016 data to assess net cure, taking into account the number of new infections, number of cures and number of HCV-related deaths.

    An annual net cure rate of 7% would be needed to meet the WHO target of eliminating HCV as a major public health concern by 2030.

    Of 210 countries globally, 91 had sufficient reporting data to be included in the analysis.

    A total of 57.3 million people were estimated to be living with HCV in the 91 countries included in the study, representing 81% of the global HCV burden. However, only eight countries in sub-Saharan Africa were included in the study.

    Regionally, the proportion of people with HCV who received DAA therapy in 2016 ranged from 8% in North America, North Africa/Middle East to just 0.1% in sub-Saharan Africa. Individual country estimates ranged from 50% in Iceland to 0.0015% in Kenya.

    For countries with over 1000 people living with HCV, Australia had the highest percentage of treated patients (16%). Ten countries had a treatment rate of over 7%, of which eight had a disease burden of over 1000 HCV patients. Four of these countries were in Western Europe. There were 44 countries with a treatment rate below 1%, including all eight countries from sub-Saharan Africa.

    Net cure rates varied considerably by country and region. In Australia, there were 29,160 cures, 830 HCV-related deaths and 5,900 new infections, meaning there were 24,090 net cures, a 12% reduction in the total epidemic size. Net cure rates ranged from 35% in Iceland to – 5.6% in Russia.

    Regionally, net cure rates ranged from 7% in North America to – 4.3% in Central and Eastern Europe.

    Ten countries had five times more people cured than new infections. In contrast, 23 countries had five times fewer people cured than new infections. This latter group included all eight countries in sub-Saharan Africa where there were 34 times more new infection than cures. Worldwide, 54 of the 91 countries had more new infections than cures.

    In the 91 countries analysed, the size of the HCV epidemic decreased in 2016 by 0.7%. When the 109 other countries with sub-optimal data collection were included, the global reduction in the size of the HCV epidemic was just 0.4%. “This is despite the $56 billion that has been spent on HCV DAAs since their launch,” write the authors.

    The overall net cure rate for the countries included in the analysis was 0.78%, with a global net cure rate of 0.48%.

    The investigators believe their findings have a number of important policy implications:

    • Current treatment rates are not high enough. More therefore needs to be done to make DAAs more affordable.
    • Further resources need to be devoted to HCV diagnosis and prevention.
    • Investment is needed in health service capacity in low- and middle-income countries so they can cope with the intensive healthcare monitoring needed during DAA therapy.

    “The inflated prices of DAAs pose a barrier to treatment in many countries,” conclude the authors.

    By Michael Carter

    Reference

    Hill AM et al. The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries. Journal of Viral Eradication, 3: 117-23, 2017.

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    FDA grants orphan drug designation to Lambda for HDV http://www.eatg.org/news/fda-grants-orphan-drug-designation-to-lambda-for-hdv/ Tue, 12 Sep 2017 21:42:57 +0000 http://www.eatg.org/?post_type=news&p=6175 FDA granted orphan drug designation to Eiger BioPharmaceuticals for its pegylated interferon lambda 1a, known as Lambda, to treat chronic hepatitis delta virus infection, according to a press release.

    Lambda, a top, late-stage type III interferon, stimulates immune responses that help develop host protection during viral infections by targeting specific receptors, according to the press release. These specific type III interferon receptors are expressed on hepatocytes with limited expression on hematopoietic and central nervous system cells, which can decrease off-target effects and increase tolerability of Lambda, per the release. Further, Lambda does not use the IFN alfa receptor, which targets type 1 interferon receptors, but signaling through either the IFN Lambda or IFN alfa receptor complexes causes the activation of the same Jak-STAT signal transduction cascade.

    Researchers have administered this potential HDV treatment in hepatitis B virus/HCV clinical trials involving more than 3,000 patients, but it has not received approval for any indication, per the press release.

    The designation of this potential HDV therapy correlates with the FDA Office of Orphan Products Development’s mission to advance the development of products and therapies that show promise for diagnosing and treating rare diseases, per the release.

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    Women with HCV face low ovarian reserve, infertility, miscarriage http://www.eatg.org/news/women-with-hcv-face-low-ovarian-reserve-infertility-miscarriage/ Tue, 12 Sep 2017 14:55:38 +0000 http://www.eatg.org/?post_type=news&p=6173 Women of child-bearing age with hepatitis C showed early signs of menopause, putting them at greater risk for infertility, gestational diabetes and miscarriage, according to a recently published study. Sustained virologic response positively impacted these outcomes.

    “We report that the relationship between HCV infection and reproductive status in women is much deeper and broader than previously thought, with profound consequences for reproductive function confirmed in cohorts from different countries,” the researchers wrote. “It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and to prevent ovarian senescence. … The effect of treatment with new generation antiviral drugs could therefore be prospectively assessed with this dual purpose.”

    To investigate the effects of HCV on ovarian function in women of childbearing age, the researchers prospectively enrolled 100 women with chronic liver disease and HCV, 50 women with chronic liver disease and hepatitis B, and 100 controls without liver disease at the University Hospitals of Modena, Turin and Naples.

    Compared with controls, patients with HCV (P = .011) and those with HBV (P = .009) had lower anti-mullerian hormone (AMH) levels, which were otherwise similar between hepatitis groups. These levels indicate lower ovarian reserve and declining ovarian function. Patients with HCV had more frequently menopausal AMH levels compared with those with HBV (OR = 11.625; 95% CI, 2.651-50.97) and with controls (OR = 5.26; 95% CI, 2.169-12.82).

    Among patients with HCV, the researchers found a correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038), and an association with miscarriage occurrence in those with a median AMH level of 1 ng/mL (OR = 2.333; 95% CI, 1.029-5.292).

    In analyzing the HCV and HBV cohorts together in comparison to the healthy controls, researchers associated only HCV infection (OR = 9.363; 95% CI, 2.569-34.123) with miscarriage.

    Of those who underwent treatment for HCV, the independent factors for nonresponse included HCV genotype 1 (OR = 2.309; 95% CI, 1.119-1.19) and lower AMH levels (OR = 3.649; 95% CI, 1.123-11.904). AMH levels continued to decrease posttreatment among those who did not achieve SVR from baseline (3.4 vs. 2 ng/mL; P < .0001), whereas those who achieved SVR had a lower miscarriage rate than those who failed antiviral therapy (32.07% vs. 63.6%; OR = 0.255; 95% CI, 0.09-0.723). The researchers noted that all of the women received interferon-based therapies and therefore direct-acting antivirals should be further evaluated for their impact on fertility.

    To compare their results, the researchers identified 6,805 U.S. women with HCV, 305 with HCV/HIV comorbidity, and 20,415 as hepatitis- and HIV-negative controls. Compared with controls, the women with HCV had higher probability of infertility (OR = 2.439; 95% CI, 2.13-2.794).

    Pregnant patients in the U.S. cohort with HCV were also more likely to report premature birth (OR = 1.336; 95% CI, 1.059-1.685) and gestational diabetes (OR = 1.24; 95% CI, 1.019-1.51), and less likely to report live birth (OR = 0.754; 95% CI, 0.622-0.913). Additionally, patients with HCV/HIV comorbidity had an even higher risk for infertility (OR = 3.635; 95% CI, 2.467-5.357).

    “A key result of our study concerns the association between HCV infection and risk of miscarriage,” the researchers concluded. “These results point to a specific relationship between HCV infection, ovarian function, and reproductive efficiency, suggesting that the premature ovarian senescence observed in [HCV-positive] women, as indicated by the early and significant AMH decline, has a profound effect on reproductive function.”

    Karampatou A, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.08.019.

    By Talitha Bennett

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    HCV therapy low among HIV/HCV patients with alcohol dependence http://www.eatg.org/news/hcv-therapy-low-among-hivhcv-patients-with-alcohol-dependence/ Tue, 12 Sep 2017 14:47:57 +0000 http://www.eatg.org/?post_type=news&p=6174 Alcohol dependence presents a significant barrier to hepatitis C treatment among patients with HIV compared with non-alcohol substance dependence, according to a presentation at the International Symposium on Hepatitis Care in Substance Users.

    According to the presentation by Kyle W. Prochno, a research coordinator from the Icahn School of Medicine at Mount Sinai, New York, alcohol-specific dependence was particularly prohibitive to HCV treatment initiation among patients with HIV, even when applying a treatment initiation-promoting intervention.

    The study comprised 53 patients with HCV/HIV coinfection who had not engaged in HCV treatment within 12 months. Mean patient age was 53.9 years, 71.7% were men, 49.1% were Hispanic and 41.5% were black. Overall, 81.1% received a diagnosis of lifetime substance dependence, including cocaine (69.8%), alcohol (47.2%) and opioids (47.2%).

    Researchers randomly assigned 28 patients to receive active intervention targeting psychosocial barriers to HCV treatment. They placed the remaining 25 patients in an “attention control” group with HIV education.

    Patients with alcohol dependence were significantly less likely to initiate HCV treatment than those without alcohol dependence (24% vs. 53.6%; P = .028), whereas the researchers observed no association between treatment initiation and those with non-alcohol substance dependence.

    After multivariable adjustment, patients with alcohol dependence were 0.13 times as likely to initiate treatment as those without after controlling for intervention technique (95% CI, 0.03-0.71).

    By Talitha Bennett

    Reference: Prochno KW. The impact of alcohol dependence on HCV treatment initiation in HIV/HCV co-infected patients. Presented at: International Symposium on Hepatitis Care in Substance Users; Sept. 6-8, 2017; New York.

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    Janssen to discontinue hepatitis C development program http://www.eatg.org/news/janssen-to-discontinue-hepatitis-c-development-program/ Mon, 11 Sep 2017 21:45:10 +0000 http://www.eatg.org/?post_type=news&p=6145

    Viral hepatitis research and development to focus on addressing significant unmet needs in chronic hepatitis B 

    CORK, Ireland, September 11, 2017 – Janssen Sciences Ireland UC (Janssen), today announced a strategic decision to discontinue further development of the investigational hepatitis C treatment regimen JNJ-4178, a combination of three direct acting antivirals – AL-335, odalasvir and simeprevir. The ongoing phase II studies with JNJ-4178 will be completed as planned, but there will be no additional development thereafter. This decision was made in light of the increasing availability of a number of highly effective therapies addressing the medical need in hepatitis C.

    “Going forward, our hepatitis R&D efforts will focus on chronic hepatitis B, where a high unmet medical need still exists.  Our scientists are energized by this challenge and our research ambition is to achieve a functional cure of hepatitis B which affects over a quarter of a billion people globally,” said Lawrence M. Blatt, Ph.D., Global Therapeutic Area Head, Infectious Disease Therapeutics, Janssen. “At Janssen, we focus our research and development on areas of greatest unmet medical need where we can combine our excellent internal science with the best available external innovation to bring optimized solutions and maximum benefit to patients.”

    Janssen pioneered the advancement of the first innovations in hepatitis C for nearly a decade when it co-developed telaprevir, a first-in-class protease inhibitor used in combination therapy for the treatment of chronic hepatitis C virus.1 In collaboration with Medivir AB, Janssen subsequently developed and launched the second generation protease inhibitor OLYSIO® (simeprevir),2 which is approved in countries around the world.

    Today, people living with hepatitis C have a much more diverse range of therapies available following a wave of innovative treatments securing approval. For most, the standard of care for hepatitis C therapy has a duration of 8-12 weeks offering a cure to around 92-100% of people treated.3

    About Janssen

    At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com and follow us at @JanssenGlobal.

    References

    1. Janssen. INCIVO® Approved in Europe Approved In Europe Offering High Cure Rates for Genotype-1 Chronic Hepatitis C Compared to Standard of Care. Available at: https://www.jnj.com/media-center/press-releases/incivo-telaprevir-approved-in-europe-offering-higher-cure-rates-for-genotype-1-chronic-hepatitis-c-compared-to-standard-treatment Last accessed: September 2017.
    2. Janssen. OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C. Available at: https://www.jnj.com/media-center/press-releases/olysio-simeprevir-receives-fda-approval-for-combination-treatment-of-chronic-hepatitis-c Last accessed: September 2017
    3. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. Journal of Hepatology. 2017: 66(1):153-194.

     

    See also:

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    ContraVir receives HBV IND approval for tenofovir exalidex (TXL™) in the US http://www.eatg.org/news/contravir-receives-hbv-ind-approval-for-tenofovir-exalidex-txl-in-the-us/ Mon, 11 Sep 2017 20:18:56 +0000 http://www.eatg.org/?post_type=news&p=6146 EDISON, N.J., Sept. 11, 2017 — ContraVir Pharmaceuticals, Inc. (NASDAQ:CTRV), a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies, announced today that the U.S. Food and Drug Administration (FDA) has approved an Investigational New Drug (IND) Application in the U.S. for its lead HBV compound, TXL™ for the treatment of chronic hepatitis B.

    Earlier this year, ContraVir announced that it had completed a Phase 1, multiple dose study in healthy subjects and a Phase 2a, 28 day study in HBV-infected patients. These studies were conducted in Thailand, a country with a high prevalence of chronic HBV infection. Having successfully achieved proof-of-concept, ContraVir intends to expand the TXL™ clinical program and initiate its first US-based clinical trial for TXL™ in the fourth quarter of 2017, pending approval by the Institutional Review Board. The study will enroll patients with severe renal impairment, and thus will generate data which we believe will further support the favorable safety profile of TXL™.

    “While we already have an existing open IND for TXL™ in HIV, the approval of the IND for TXL™ in HBV, is a significant step to further drive the expansion of our development program,” said James Sapirstein, Chief Executive Officer of ContraVir. “We are particularly excited about this news, as it broadens the reach of our clinical program and allows us to conduct co-development programs in the U.S. for patients with both HIV and HBV infection.”

    About TXL™

    Tenofovir exalidex (TXL™) is a highly potent prodrug of the antiviral tenofovir.  Tenofovir is the active component of both Vemlidy (tenofovir alafenamide) and Viread® (tenofovir disoproxil fumarate).TXL’s novel liver-targeting prodrug structure results in decreased systemic circulating levels of tenofovir, thereby reducing the potential for renal and bone side effects. ContraVir has completed a Phase 2 trial of TXL™, in which HBV-infected subjects were administered doses up to 100 mg for 28 days and is now optimizing its formulation to further enhance drug delivery. To date, TXL™ has achieved clinical proof of concept for antiviral activity and displayed an excellent safety, tolerability, and pharmacokinetic profile. Based on the agent’s best-in-class potential, ContraVir believes TXL™ can become the cornerstone of a curative combination therapy for hepatitis B.

    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 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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    HCV treatment found safe and effective in individuals with kidney disease http://www.eatg.org/news/hcv-treatment-found-safe-and-effective-in-individuals-with-kidney-disease/ Mon, 11 Sep 2017 18:05:40 +0000 http://www.eatg.org/?post_type=news&p=6143 Highlights

    • In patients with chronic kidney disease and Hepatitis C virus infection, sofosbuvir-based direct-acting antiviral therapy was safe and effective.
    • Patients with stage 3 kidney disease who were cured of infection experienced an improvement in their kidney function following treatment.
    • Hepatitis C virus infection, the most frequent chronic viral infection in the United States, is a common comorbidity in patients with chronic kidney disease.

    Washington, DC (September 7, 2017) — A new study indicates that direct-acting antiviral therapy is safe and effective in patients with chronic kidney disease (CKD) and Hepatitis C virus (HCV) infection. The study, which appears in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN), also found that treatment may help improve some patients’ kidney function.

    HCV infection–which often causes liver disease–is common in patients with CKD, and it increases their risk of progressing to kidney failure. Sofosbuvir is a potent direct-acting antiviral therapy against HCV, but concerns about potential kidney toxicity have been raised, particularly in patients with CKD.

    To determine the safety and efficacy of sofosbuvir in patients with CKD, Meghan Sise, MD, MS (Massachusetts General Hospital) and her colleagues studied 98 patients with stages 1-3 CKD who received sofosbuvir-based therapy in a large healthcare system.

    Overall sustained virologic response (which is synonymous with cure of HCV infection) was 81%, and average kidney function while on the treatment was stable. Patients with more advanced CKD were more likely to be cured of HCV infection than those with mild CKD. In addition, patients with advanced CKD who were cured of HCV infection experienced an improvement in their kidney function following treatment. Sofosbuvir was reasonably well tolerated: adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon. Also, there was no detectable effect of the degree of CKD on the rate of adverse events.

    Larger studies are needed to determine if eradication of HCV with direct-acting antiviral therapy slows or prevents progression to end stage kidney disease in patients with CKD and HCV.

    “The use of direct-acting antiviral therapy in patients with Hepatitis C infection has transformed the illness into a curable one. This study shows that these medications can be safely and effectively used in patients with stage 1-3 kidney disease,” said Dr. Sise.

    In an accompanying editorial, Richard Johnson, MD (University of Colorado) and Michiko Shimada, MD, PhD (Hirosaki University Graduate School of Medicine, in Japan) noted that there are other antiviral drugs that are effective in patients with CKD and HCV, and unlike sofosbuvir, they are not eliminated by the kidneys. Therefore, additional research on the effects of different antivirals in patients with compromised kidney function are needed. “We predict that HCV, like hepatitis B virus and HIV, will slowly disappear as a major medical problem for patients with renal disease,” they wrote.

    ###

    The article, entitled “Effect of Sofosbuvir-based Hepatitis C Virus Therapy on Kidney Function in Patients with Chronic Kidney Disease,” will appear online at http://cjasn.asnjournals.org/ on September 7, 2017, doi: 10.2215/CJN.02510317.

    The editorial, entitled “Contemporary Management of Hepatitis C in Patients with CKD,” will appear online at http://cjasn.asnjournals.org/ on September 7, 2017.

     

    See also:

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    Injection drug users with HCV in Scotland lack awareness of DAA efficacy http://www.eatg.org/news/injection-drug-users-with-hcv-in-scotland-lack-awareness-of-daa-efficacy/ Mon, 11 Sep 2017 15:26:02 +0000 http://www.eatg.org/?post_type=news&p=6148 Most people who inject drugs were not aware of currently available, highly effective hepatitis C treatments, according results of a national survey in Scotland presented at the International Symposium on Hepatitis Care in Substance Users.

    From 2015 to 2016, researchers surveyed 2,623 individuals who attended injection equipment provision sites to assess the awareness of new direct-acting antivirals and their efficacy among injection drug users and to determine the factors associated with awareness.

    Overall, 879 of the participants had chronic HCV, 36% of whom were unaware of their infection. While 90% of all participants were treatment naive, 79% were aware of HCV treatment.

    Researchers asked, “What are the chances of hepatitis C being cured with current treatment?” Most participants (n = 530) responded that the chance was low or less than 40%, followed by 183 who answered very high or 81% to 100%, 127 who answered high or 61% to 80%, and 39 who answered that the chances were reasonable or 41% to 60%.

    In an adjusted analysis, participants previously tested for HCV were more likely to be aware of treatment than those who had not among both uninfected (OR = 3.11; 95% CI, 2.3-4.22) and infected participants (OR = 16.04; 95% CI, 10.57-24.33).

    Additionally, awareness of DAA effectiveness was significantly higher among those who had ever attended a clinic (OR = 9.76; 95% CI, 5.13-18.6), been diagnosed but never attended a clinic (OR = 3.91; 95% CI, 2.02-7.53), and been tested but were uninfected (OR = 2.55; 95% CI, 1.35-4.81) compared with those who had never received a test.

    The researchers concluded by advocating for increased efforts to raise awareness of new HCV therapies and the effective outcomes of new DAAs among high-risk populations such as injection drug users.

    By Talitha Bennett

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    Among injection drug users in San Francisco, young adults at highest risk for HCV http://www.eatg.org/news/among-injection-drug-users-young-adults-at-highest-risk-for-hcv/ Mon, 11 Sep 2017 14:29:21 +0000 http://www.eatg.org/?post_type=news&p=6149 Adult injection drug users aged 30 years or younger are both at the highest risk for acquiring hepatitis C and transmitting HCV, according to a presentation at the International Symposium on Hepatitis Care in Substance Users.

    Kimberly Page, PhD, MPH, MS, from the University of New Mexico Health Sciences Center, presented results from the Acute UFO study, which took place from 2003 to 2017 in San Francisco. According to Page, HCV incidence has been increasing among young injection drug users in general, and has increased in both urban and especially non-urban areas.

    To assess the association between injecting user’s partner age and risk for HCV in injecting partnerships, the researchers prospectively gathered demographic, HCV risk behavior and injecting partnership data from 391 people who inject drugs.

    All participants were negative for HCV according to anti-HCV and HCV RNA testing and reported one to three injecting partnerships (n = 909). Median age of participants was 24 years (range, 22-27 years). During follow-up, 99 participants developed HCV for an overall incidence rate of 27.8 per 100 person-years (95% CI, 22.9-33.9).

    Sixty-seven participants reported that all their partners in the last 3 years were aged 30 years or older, 145 reported a mix of partner ages, and 179 reported that all their partners were younger than 30 years. While 60 participants reported that all their partners were HCV-negative, 150 reported that at least one partner was HCV-positive and 181 reported they were unaware of the HCV status of at least one partner.

    From 2006 to 2017, the participants’ HCV incidence rate was highest among those with partners all younger than 30 years (34.5 per 100 person-years; 95% CI, 26-45.8), followed by those with mixed-age partners (27.1 per 100 person-years; 95% CI, 19.9-37) and those with partners all aged 30 years or older (15.9 per 100 person-years; 95% CI, 8.8-28.7).

    In a multivariable model, the researchers observed the lowest incidence in participants whose partners were all aged 30 years or older and had at least one known partner with HCV (P = .06).

    In her conclusion, Page advised that the protective factors at work among the relationships including older partners requires further exploration. Additionally, disclosure of HCV status within partnerships has potential to increase preventive behaviors and potentially reduce HCV incidence.

    By Talitha Bennett

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    People who use drugs require prioritization, not exclusion, in HCV elimination http://www.eatg.org/news/people-who-use-drugs-require-prioritization-not-exclusion-in-hcv-elimination/ Thu, 07 Sep 2017 21:00:44 +0000 http://www.eatg.org/?post_type=news&p=6130 An international conference bringing together hepatitis C experts from around the world is today calling for strategies to prioritise people who use drugs, saying hepatitis C elimination is impossible without them.

    “The number of people around the world dying from hepatitis C is increasing. We have the tools to reverse this trend, to eliminate this disease and save millions of lives. But it will not happen until people who use drugs become a focus of our efforts,” said Associate Professor Jason Grebely, President of the International Network of Hepatitis C in Substance Users (INHSU), the convenors of the conference.

    Hepatitis C is a blood borne virus that if left untreated can result in cirrhosis, liver cancer, and liver failure. Globally, there is an estimated 71.1 million people with chronic hepatitis C, resulting in over 700 000 deaths each year and the numbers are increasing. Eight per cent of those living with the disease and almost a quarter of new infections are in people who use drugs.

    New, highly effective curative treatments have sparked hope of a world free of hepatitis C. Countries like Australia are currently on track to eliminate the disease as a public health concern by 2026 thanks to a public health strategy that offers treatment to all without restriction, and the prioritisation of people who use drugs. However in the US and many countries globally, hepatitis C testing, linkage to care, and treatment for people who use drugs remain low.

    Why treat?

    • It is essential for elimination. Without treatment for people who use drugs, elimination of hepatitis C will be impossible as the disease prevalence in this group is simply too high.
    • It can be cost effective compared with delaying until the development of cirrhosis, decompensated liver disease, and liver cancer.
    • It will reduce onward transmission: Studies from Scotland, Australia and Canada indicate that a 3 to 5 fold increase in the number of people who inject drugs on treatment could reduce chronic hepatitis C prevalence by 15-50% within a decade.
    • It works. Recent evidence shows that new hepatitis C cures are just as effective in people who use drugs as other populations and that reinfections levels are low.

    Experts at the 6th International Symposium on Hepatitis Care in Substance Users say that to be successful, elimination of hepatitis C in people who use drugs requires careful integration with harm prevention programs and linkage to care, as well as a review of policies that drive disease spread.

    Research being presented at the conference demonstrates that:

    • Opioid Substitution Therapy (OST) and Needle and Syringe Programs (NSP) can reduce hepatitis C incidence by up to 80%.
    • Response to new hepatitis C DAA treatment among people who use drugs is high and reinfection is low.
    • Community involvement is key to successful program implementation.

    “Access to good quality healthcare should be a basic human right for any person, irrespective of whether they use drugs, ” said A/Prof. Grebely. “But when providing this also means we are able to eliminate a disease currently affecting 71 million people around the world, then taking action becomes even more of a moral and public health imperative. We cannot afford to delay any longer.”

    ABOUT THE CONFERENCE

    The 6th International Symposium on Hepatitis Care in Substance Users is the leading international conference focused on the management of hepatitis among substance users. It is organized by the International Network for Hepatitis in Substance Users (INHSU). The symposium has been previously held in Zurich, Brussels, Munich, Sydney and Oslo. The 6th International Symposium on Hepatitis Care in Substance Users is taking place in New York.

    Follow us on twitter #INHSU17

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    Unitaid publishes Technology and Market Landscape for Hepatitis C Medicines http://www.eatg.org/news/unitaid-publishes-technology-and-market-landscape-for-hepatitis-c-medicines/ Wed, 06 Sep 2017 21:32:00 +0000 http://www.eatg.org/?post_type=news&p=6114 Geneva, 06 September 2017 The World Health Organization (WHO) estimates that 71 million people worldwide are chronically infected with Hepatitis C virus (HCV). Of those, 2.3 million people are co-infected with the human immunodeficiency virus (HIV) and HCV. In 2015, around 400,000 people died of HCV-related liver disease, and the global HCV burden is increasing.

    Unitaid’s Technology and Market Landscape for Hepatitis C Medicines reviews the current global market for direct-acting antivirals (DAAs), which have revolutionized treatment for HCV. Combinations of direct-acting antivirals are highly effective; they can cure HCV infection in 12 weeks, and have limited side-effects. Combinations that are effective against all genotypes of HCV have started to become available. These pan-genotypic combinations can contribute to simplifying diagnostics and treatment, and could enable treatment to be introduced in resource-limited settings.

    The first part of Unitaid’s report, on technology, reviews the various medicines and combinations now available to treat HCV and looks forward to regimens currently in development.

    The second part of the report surveys the market for direct-acting antivirals, which is relatively new in low- and middle-income countries. Ensuring a robust supply of HCV drugs can be a challenge, with various market forces affecting their procurement and uptake. Though the market for generic direct-acting antivirals has developed fast, it remains fragile.

    The report also asks how best to prioritize high-risk groups for HCV screening, diagnosis and treatment.  Some “pathfinder” countries are reportedly considering this approach. Groups at high risk for HCV infection include, among others, people living with HIV, people who inject drugs, prisoners and children born to HCV-positive mothers.

    Offering HCV screening in, for instance, clinics for antiretroviral therapy and harm reduction services may make it easier to find HCV-positive patients, and to reduce new infections, the report concludes.

    Read the report:

    Technology and Market Landscape for Hepatitis C Medicines (2017)

    Previous reports:

    All Unitaid’s Hepatitis C publications

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    Cirrhosis is linked with hepatitis C treatment failure among those who also have HIV http://www.eatg.org/news/cirrhosis-is-linked-with-hepatitis-c-treatment-failure-among-those-who-also-have-hiv/ Wed, 06 Sep 2017 21:13:02 +0000 http://www.eatg.org/?post_type=news&p=6125 Researchers identified this association after looking at real-world data on a large group of German individuals with HIV and hep C.

    Among people coinfected with HIV and hepatitis C virus (HCV), hep C treatment is more likely to fail among those who have cirrhosis of the liver.

    In numerous clinical trials, the modern crop of HCV treatments, known as direct-acting antivirals (DAAs), have shown comparable cure rates among those who do and do not also have HIV. However, in two recent cohorts of Spanish individuals receiving treatment for hep C, the subgroups that had HIV in each cohort did experience somewhat lower cure rates compared with the subgroups that had only HCV, specifically cure rates of 92 percent and 95 percent among those with HIV and HCV compared with cure rates of 98 percent and 98 percent among those with only HCV.

    Looking to identify risk factors that might influence such differences in cure rates, researchers studied data on 1,505 members of the real-world German hepatitis C cohort (GECCO), all of whom were treated for HCV with one of the following DAA-based regimens: interferon, ribavirin and Sovaldi (sofosbuvir); Sovaldi and ribavirin; Sovaldi and Olysio (simeprevir); Sovaldi and Daklinza (daclatasvir) with or without ribavirin; Harvoni (ledipasvir/sofosbuvir); and the Viekira regimen (ombitasvir/paritaprevir/ritonavir; dasabuvir) with or without ribavirin.

    Findings were published in Open Forum Infectious Diseases.

    Sixty-three percent of the cohort members were male. The median age was 52. Seventy-two percent had genotype 1 of hep C, 4 percent had genotype 2, 18 percent had genotype 3 and 6 percent had genotype 6. Twenty percent had a hep C viral load above 6 million before treatment. Forty-six percent had been treated for hep C before. Nineteen percent were on opioid substitution therapy.

    Twenty-three percent (349 of 1,505) of the cohort had HIV. Of those with HIV, 20 percent were diagnosed with that virus when they already had AIDS. Seventeen percent had a CD4 count below 350 before beginning HCV treatment. The median lowest-ever CD4 count was 206. Ninety-nine percent were on antiretroviral (ARV) treatment for HIV, and 92 percent had a fully suppressed HIV viral load. The median time that people with HIV took ARVs before undergoing HCV treatment was 6.4 years.

    Those living with HCV (known as being monoinfected), compared with those living with HIV and HCV (coinfected), were significantly more likely to be male (89 percent versus 55 percent), less likely to have genotype 3 of hep C (9 percent versus 21 percent), more likely to have genotype 4 (18 percent versus 3 percent), more likely to have a hep C viral load above 6 million (27 percent versus 17 percent) and less likely to have cirrhosis (22 percent versus 31 percent).

    Overall, 95 percent of the study cohort, including those with and without HIV, achieved a sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure of HCV). A respective 94 percent and 95 percent of those with and without HIV were cured of hep C; this difference was not statistically significant, meaning it could have occurred by chance.

    Ten individuals in the overall cohort stopped hep C treatment early, including one whose virus did not respond to treatment, two who experienced viral breakthrough in which their virus returned during treatment and seven who experienced medication-related toxicities, including difficulty breathing or labored breathing (dyspnea), rash, panic attacks, insomnia and nausea. None of the cohort members experienced grade 3 or 4 adverse health events based on the results of laboratory tests. After completing treatment, three people were reinfected with hep C, and 67 saw their virus return.

    Looking at data on the 349 coinfected individuals, the researchers did not find that the following factors were associated with differences in hep C cure rates: sex, age, genotype, high hep C viral load, ALT (a measure of liver enzymes), previous experience with hep C treatment, lowest-ever CD4 count and use of opioid substitution therapy.

    Those with a CD4 count below 350 and those with cirrhosis were less likely to achieve a cure for hep C. After adjusting the data for various factors, the researchers found that having cirrhosis increased by 3.5-fold the likelihood that those with HIV/HCV coinfection would not be cured of hep C through DAA treatment. A lower CD4 count was no longer statistically significantly associated with treatment failure in this adjusted analysis.

    To read the study abstract, click here.

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    Hepatitis B: Search for the cure and challenges that remain http://www.eatg.org/news/hepatitis-b-search-for-the-cure-and-challenges-that-remain/ Mon, 04 Sep 2017 21:12:43 +0000 http://www.eatg.org/?post_type=news&p=6095 The World Health Organization (WHO) estimates that approximately 257 million people worldwide are living with hepatitis B virus (HBV) infection.1 In 2015, hepatitis B claimed 887,000 lives, mostly due to complications such as liver cancer and cirrhosis.

    The most common routes of transmission of HBV in children are perinatally, from mother to child, and, horizontally, from an infected child to an uninfected child during the first 5 years of life.1 The earlier in life the infection occurs, the greater the chance of chronicity;2 in infants, HBV infection will progress to chronic infection in approximately 90% of cases.3

    The chronic nature of the disease acquired early in childhood often requires lifestyle changes; treatment with oral antivirals such as tenofovir or encetavir that work by suppressing the replication of the virus; and close monitoring to prevent the development of potentially fatal complications, such as hepatic decompensation, hepatocellular carcinoma, and cirrhosis. The incidence rate of disease progression to these 3 complications is estimated at 15% to 40%.4

    After effective hepatitis B vaccines became available in the early 1980s, universal infant immunization, regardless of the presence or absence of maternal infection, has been recommended at birth.3

    In an interview with Infectious Disease Advisor, Chari Cohen, DrPH, MPH, director of public health and deputy executive director at the Hepatitis B Foundation in Doylestown, Pennsylvania, discussed the challenges associated with managing chronic hepatitis B infection today, as well as the latest developments in the search for a cure.

    Infectious Disease Advisor: How has the development of the hepatitis B vaccine transformed the lives of people at risk for hepatitis B around the world?

    Chari Cohen DrPH, MPH: The hepatitis B vaccine is the first anti-cancer vaccine, because it prevents liver cancer. Hepatitis B is an important human carcinogen, and is second only to tobacco in the number of cancer cases and deaths that it causes.5 So, the advent of the hepatitis B vaccine has had a tremendous impact on preventing infection and breaking the cycle of infection for future generations. More than 1 billion doses of the hepatitis B vaccine have been given worldwide and it is considered one of the safest and most effective vaccines ever made.6 Preventing new hepatitis B infections not only reduces illness and death associated with hepatitis B — which causes up to 877,000 global deaths each year — but it saves money.7 It is far more cost effective to prevent new hepatitis B infections than it is to treat chronic hepatitis B, cirrhosis, or liver cancer. Prevention of hepatitis B infection equals lives saved.

    Infectious Disease Advisor: How effective is vaccination in preventing hepatitis B infection?

    Dr Cohen: The vaccine offers long-term protection in more than 90% of healthy people who are vaccinated.8,9 It is important to remember, however, that even with the vaccine, there are still 257 million people living with hepatitis B globally,7 and thousands of people are newly infected each day. There are critical systemic barriers worldwide that prevent us from ensuring that everyone, especially individuals at high risk for infection, receives the vaccine. This is a particular unmet need in babies born to mothers who are infected, as the hepatitis B virus can be transmitted from mother to child during childbirth. Administering a dose of hepatitis B vaccine within 12 to 24 hours of birth can prevent most babies from getting infected, but the birth dose administration rate worldwide remains low, at 39%.7 The World Health Organization (WHO)  has set a goal to eliminate viral hepatitis by 2030. Without more effectively ensuring that the hepatitis B vaccine birth dose is routinely given, especially in high-risk countries around the world, we will not be able to eliminate hepatitis B from the globe — even though we have the tools to do it.

    Infectious Disease Advisor: What are some of the challenges associated with managing chronic hepatitis B infection today?

    Dr Cohen: Chronic hepatitis B infection can lead to liver failure, cirrhosis and liver cancer over time. In fact, up to 25% of people who have chronic hepatitis B will die prematurely from hepatitis B-related liver disease without intervention.10 The current US Food and Drug Administration (FDA)-approved antiviral medications for chronic hepatitis B infection can be effective at slowing down viral replication in liver cells, which can often lead to less liver damage over time.11 So, current antiviral treatment can slow down or prevent progression to liver disease such as cirrhosis or liver cancer in many people who are treated. However, these medications aren’t effective in everyone who has chronic hepatitis B infection. And these medications are not curative – they are long-term treatments, which most often need to be taken for many years, often for life – and they rarely rid the body of the virus.

    Furthermore, while someone is taking antiviral medications for hepatitis B infection they need to be monitored on an ongoing basis by a healthcare provider. It can be difficult for people to continue to visit a healthcare provider and take daily medication for many years – in many countries there is a lack of healthcare infrastructure for this type of care. In the United States, many of the communities on which hepatitis B has a disproportionate impact have limited access to healthcare (and medicine) due to multiple barriers, including under-insurance. For these reasons (and others), it is critical that we find a cure for hepatitis B.

    There are many barriers to receiving treatment that need to be overcome. Worldwide, only 9% of infected individuals are aware of their infection, and only 8% receive treatment.7 In the United States, only 30% to 35% of infected individuals are diagnosed, and 5% receive treatment.12 We clearly need to do a better job identifying and managing people with hepatitis B infection.

    Infectious Disease Advisor: What is the main focus of the research effort aimed at developing a cure for hepatitis B?

    Dr Cohen: Recently, the Hepatitis B Foundation convened more than 30 of the world’s leading experts, and together we developed a Research Agenda for Curing Hepatitis B Virus Infection.13 This “Roadmap for a Cure” highlights priority areas for hepatitis B and liver cancer research, to see improved health outcomes in the millions of people living with chronic hepatitis B infection. The research agenda for a cure points out broad areas of research efforts that are needed, including: expanding our understanding of hepatitis B virology and immunology; developing antiviral therapies and immunological approaches to repress and eliminate hepatitis B in infected cells; and developing an improved understanding of the molecular pathways leading to liver cancer, to find new methods of early detection and management of liver cancer.13

    In terms of developing new therapeutics, the current FDA-approved antiviral medications for hepatitis B all work by inhibiting viral replication. However, there are other possible targets within the virus life cycle that need to be explored.14 For example, most agree that there is a need to prioritize research to understand the biology of hepatitis B covalently close circular DNA (cccDNA). cccDNA comes from the viral genome and it persists in liver cells. It can cause the virus to rebound after current antiviral therapies are stopped, which is why people with chronic hepatitis B infection often cannot discontinue their medication. It is thought that if we can target and suppress cccDNA, we might be on the fastest route to a cure. Little is currently known about cccDNA, but this is considered high priority research.13

    Infectious Disease Advisor: Are any promising drug candidates already being tested in clinical trials?

    Dr Cohen: Yes, there are many promising new drugs coming down the pipeline. For a list of drugs in development for chronic hepatitis B infection, please visit the Hepatitis B Foundation Drug Watch. You can also search for hepatitis B clinical trials on our Clinical Trials page. If you want to learn more about the current and future of hepatitis B cure research, you can view a video webinar featuring Dr Timothy Block, co-founder and president of the Hepatitis B Foundation and president and director of the Baruch S. Blumberg Institute.

    By Jasenka Piljac Žegarac

    References

    1. World Health Organization (WHO). Hepatitis B fact sheet. www.who.int/mediacentre/factsheets/fs204/en/.  Reviewed July 2017. Accessed August 5, 2017.
    2. Chang MH. Hepatitis B virus infection. Semin Fetal Neonatal Med. 2007;12:160-167.
    3. Jourdain G, Ngo-Giang-Huong N, Cressey TR, et al. Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen. BMC Infect Dis. 2016;16:393.
    4. Borgia G, Carleo MA, Gaeta GB, et al. Hepatitis B in pregnancy. World J Gastroenterol. 2012;18(34):4677-4683.
    5. World Health Organization (WHO). Hepatitis. www.who.int/biologicals/areas/vaccines/hepatitis/en/. Accessed August 9, 2017.
    6. Hepatitis B Foundation. Vaccination. www.hepb.org/prevention-and-diagnosis/vaccination/. Accessed August 9, 2017.
    7. World Health Organization (WHO). Global hepatitis report, 2017. www.who.int/hepatitis/publications/global-hepatitis-report2017/en/. Published April 2017. Accessed August 9, 2017.
    8. Zajac BA, West DJ, McAleer WJ, et al. Overview of clinical studies with hepatitis B vaccine made by recombinant DNA. J Infect. 1986;13(Suppl A):39-45.
    9. Andre FE. Summary of safety and efficacy data on a yeast-derived hepatitis B vaccine. Am J Med. 1987;87(Suppl 3A):S14-S20.
    10. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2001;34(6):1225‐1241.
    11. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661‐662.
    12. Cohen C, Holmberg S, McMahon BJ, et al. Is chronic hepatitis B being undertreated in the United States? J Viral Hepat. 2011;18(6):377‐383.
    13. Hepatitis B Foundation. Conquering hepatitis B now! An overview of a Roadmap for a Cure. http://hepbunited.org/wp-content/uploads/2017/06/May-24-Briefing-Agenda_external_with-logos-1.pdf. Accessed August 9, 2017.
    14. Block TM, Gish R, Guo H, et al. Chronic hepatitis B: what should be the goal for new therapies? Antiviral Res. 2013;98(1):27-34.
    ]]>
    VBI Vaccines to advance Phase 3 study for Sci-B-Vac http://www.eatg.org/news/vbi-vaccines-to-advance-phase-3-study-for-hepatitis-b-vaccine-sci-b-vac/ Sat, 02 Sep 2017 12:38:26 +0000 http://www.eatg.org/?post_type=news&p=6079 VBI Vaccines announces FDA acceptance of Investigational New Drug Application for Sci-B-Vac® Phase 3 clinical program

    — Sci-B-Vac® is a third-generation hepatitis B vaccine, approved for use in Israel and 14 other countries
    — VBI expects to initiate enrollment in a Phase 3 clinical program later in the second half of 2017 in the U.S., Europe and Canada

    August 30, 2017 – VBI Vaccines Inc. (Nasdaq: VBIV) (TSX: VBV) (VBI) today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug Application (IND) for a Phase 3 clinical program evaluating Sci-B-Vac®, VBI’s third-generation hepatitis B vaccine. The company had previously received a No Objection Letter (NOL) from Health Canada in response to its Clinical Trial Application (CTA) as well. Acceptance of the IND and CTA enable the company to initiate the Phase 3 clinical study in both the U.S. and Canada.

    “The receipt of formal acceptance of our clinical program from both the FDA and Health Canada marks a significant milestone as we move forward to initiating enrollment later this year in this Phase 3 pivotal program,” said Jeff Baxter, President and CEO of VBI. “This program is expected to be conducted at approximately 40 sites across the U.S., Canada and Europe.”

    VBI previously announced the design of its 4,800-subject clinical program which will consist of two concurrent, 15-month Phase 3 studies – a safety and immunogenicity study (PROTECT) and a lot-to-lot consistency study (CONSTANT).

    About PROTECT – Safety and Immunogenicity Study

    PROTECT will be a double-blind, two-arm, randomized, controlled study. Approximately 1,600 adult subjects, age 18 years 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 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 more than 300,000 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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    Immune response to hepatitis B vaccination in HIV-positive individuals with isolated anti-HBc http://www.eatg.org/news/immune-response-to-hepatitis-b-vaccination-in-hiv-positive-individuals-with-isolated-anti-hbc/ Sat, 02 Sep 2017 09:10:30 +0000 http://www.eatg.org/?post_type=news&p=6086 Results of a prospective Italian study

    Abstract

    Background and aim

    Antibodies against hepatitis B core antigen (anti-HBc) are found in 14–44% of patients with HIV infection, but it is still unclear whether hepatitis B virus (HBV) vaccination should be recommended for HIV-positive subjects with isolated anti-HBc (IAHBc). We examined the rate of anamnestic and primary responses (ARs and PRs) and associated factors in a group of HIV-infected patients with an IAHBc profile.

    Methods

    This prospective study recruited 25 HIV-positive patients with anti-HBc alone who were vaccinated against HBV infection. Those without an AR (anti-hepatitis B envelope antigen [anti-HBs] levels of <10 U/L) or who were hypo-responsiveness (anti-HBs levels of >10 but <100 U/L) four weeks after the first dose of vaccine underwent a full course of vaccinations. Their clinical and virological data, including the presence of occult hepatitis B infection (OBI), were evaluated in accordance with the vaccination schedule.

    Results

    Six of the 25 patients (24%) showed an AR, four of whom had anti-HBs levels of <100 U/L. Ten of 19 (52.6%) remaining patients became seroprotected after the third dose. OBI was detected in four of the six patients with an AR, two of the 10 patients with a PR, and none of the nine patients who did not respond. Multivariate analysis showed that an AR was associated with the presence of OBI (P = 0.0162), and a PR was associated with HCV antibody status. (P = 0.0191).

    Conclusions

    Our data suggest that testing for anti-HBc alone may not be a reliable means of assessing protection from HBV infection in HIV-positive patients. OBI-positive patients may benefit from a single vaccine dose. Anti-HCV serostatus may affect PRs.

    Read the full study here.

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    Risk of HBV reactivation low in DMARD users http://www.eatg.org/news/risk-of-hbv-reactivation-low-in-dmard-users/ Sat, 02 Sep 2017 09:05:25 +0000 http://www.eatg.org/?post_type=news&p=6075 More common with chronic versus resolved infection

    Hepatitis B virus (HBV) reactivation was unlikely in patients receiving disease-modifying antirheumatic drugs (DMARDs) whose HBV infection had resolved, according to a meta-analysis.

    The rate of HBV reactivation was substantially higher in patients with chronic HBV infection without antiviral prophylaxis. Among patients with resolved HBV infection, the rate of reactivation was similar between patients receiving tumor necrosis factor (TNF) inhibitors, non-TNF biologic agents, and nonbiologic DMARDs, reported Daniel Solomon, MD, MPH, of Harvard Medical School in Boston, and colleagues.

    “We found that among all inflammatory arthritis patients with resolved hepatitis B receiving DMARDs of any type without antiviral prophylaxis, the HBV reactivation rate was low (1.6%) and remained low in DMARD subgroups,” they wrote in Arthritis Care & Research.

    The American Gastroenterological Association in its 2015 guidelines states that the risk of hepatitis B reactivation in patients with inflammatory arthritis using non-biologic DMARDs is generally <1%.

    Patients with chronic HBV have a five- to eight-fold greater risk for hepatitis B reactivation than patients with resolved HBV. With the advent of biologic immunomodulators, evidence had emerged to suggest that hepatitis B reactivation was associated with use of TNF inhibitors in inflammatory arthritis. Hepatitis B reactivation can largely be prevented by HBV screening before starting immunomodulators “and by initiating anti-viral prophylaxis in patients with chronic HBV infection,” the authors noted.

    Several large observational studies have been published since a previous meta-analysis in 2014 examining the risk of hepatitis B reactivation in patients with resolved or chronic HBV infection. That meta-analysis found that the overall pooled hepatitis B reactivation rate was 3.0% in patients with inflammatory arthritis who had resolved HBV infection and 15.4% in those with chronic HBV infection.

    Solomon’s group sought to provide more precise estimates of reactivation rates in patients receiving biologic or nonbiologic DMARDs and with or without antiviral prophylaxis.

    They included 25 studies in their meta-analysis, in which 1,032 patients with resolved and 259 with chronic HBV infection were identified. Reactivation was defined by seroconversion from HBsAg-negative at baseline to HBsAG-positive during follow-up, detectable HBV DNA during follow-up after undetectable HBV DNA at baseline or a >1 log increase in HBV during follow-up.

    The pooled estimate for HBV reactivation in patients with resolved HBV infection was 1.6% (95% CI 0.8-2.6%) overall. The estimates were 1.4% in patients who received TNF inhibitors, 6.1% in those who received non-TNF biologic DMARDs, and 1.7% in users of nonbiologic DMARDs.

    Seven studies reported HBV reactivation rates in patients with chronic HBV reactivation without antiviral prophylaxis and seven with antiviral prophylaxis.

    The pooled reactivation rates in patients with chronic HBV infection were 9.0% in those receiving antiviral prophylaxis and 14.6% without antiviral prophylaxis. Reactivation rates were 4.4% versus 15.6%, respectively, in the subgroup receiving TNF inhibitors. Reactivation rates in the chronic HBV infection group were similar with and without antiviral prophylaxis in the subgroup receiving nonbiologic DMARDs (27.1% versus 22.4%, respectively).

    Significant heterogeneity was found in the overall pooled estimates of the DMARDs with antiviral prophylaxis (P =0.02 for heterogeneity) and without antiviral prophylaxis groups (P<0.001 for heterogeneity).

    A sensitivity analysis in a subgroup of patients who consistently received antivirals during follow-up revealed a much lower reactivation rate than the primary analysis in recipients of nonbiologic DMARDs (pooled estimate 14.8%, 95% CI, 2.6-32.9, P=0.58 for heterogeneity) and lower than patients who did not receive antivirals.

    Use of the combination of nonbiologic DMARDs and glucocorticoids was common in included studies. “We found a similar reactivation risk between combination of nonbiologic DMARDs and glucocorticoids (1.7%) and TNF inhibitors (1.4%),” the authors wrote. “This finding is higher than expected (~1%) from the American Gastroenterological Association 2015 guideline and urges the awareness from physicians, as combination of nonbiologic DMARDs and glucocorticoids is a common choice for rheumatoid arthritis patients with moderate to high disease activity.”

    Study limitations included the fact all of the included studies were observational and non-controlled. Also, there was the possibility of misclassification of DMARD exposure, which was based on baseline information only.

    Solomon disclosed support from the NIH, and relevant relationships with Amgen, Astra Zeneca, Bristol-Myers Squibb, Eli Lily, Pfizer, and Genentech.

    By Wayne Kuznar

    Primary Source
    Arthritis Care & Research
    Source Reference: Lin Tc, et al “Risk of hepatitis B reactivation in inflammatory arthritis patients receiving disease modifying anti-rheumatic drugs (DMARDs): a Systematic Review and Meta-analysis” Arth Care Res 2017.

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    Higher FIB-4 index in patients with HBV linked to increased HCC risk http://www.eatg.org/news/higher-fib-4-index-in-patients-with-hbv-linked-to-increased-hcc-risk/ Sat, 02 Sep 2017 08:59:53 +0000 http://www.eatg.org/?post_type=news&p=6077 In a cohort of patients with chronic hepatitis B without cirrhosis, the risk for hepatocellular carcinoma was significantly higher among those with a FIB-4 index over 1.29, according to recently published data.

    “Implementation of HCC surveillance is important because it is the only way to identify HCC at an early stage, which reduces disease-related morbidity and mortality,” Tai-Chung Tseng, MD, PhD, from the National Taiwan University Hospital Jinshan Branch, and colleagues wrote. “On the basis of our data, the patients with baseline FIB-4 index [lower than] 1.29 and a favorable clinical profile did not develop HCC within 16 years of follow-up. This finding helps practicing physicians identify the patients with the lowest HCC risks, who may not have additional benefit from HCC surveillance.”

    To confirm the role of FIB-4 index in association with HCC risk, the researchers enrolled 2,075 treatment-naive adults with chronic HBV without cirrhosis. Additionally, the study comprised a validation cohort of 532 patients who received long-term nucleos(t)ide analogue (NUC) treatment from 2004 to 2012.

    Mean FIB-4 was 1.11 (range, 0.23-6.65). During follow-up, 137 patients developed HCC with an incidence rate of 0.41 cases per 100 person-years.

    All patients with an FIB-4 index over 1.29 had an increased risk for HCC (HR = 5.56; 95% CI, 3.93-7.86) vs. those with an index below 1.29. The cut-off of an index higher than 1.29 remained significant after adjusting for age, sex, alanine aminotransferase and aspartate aminotransferase, HBeAg, genotype, HBV DNA and HBsAg levels (HR = 2.27; 95% CI, 1.26-3.8).

    Patients in the validation cohort received long-term NUC treatment for a mean of 6.69 years (range, 1.28-11.88 years). Ten of these patients developed HCC with an incidence rate of 0.27 cases per 100 person-years. The researchers observed that FIB-4 index higher than 1.29 at both baseline (P = .023) and 1-year (P < .001) was significantly correlated with higher risk for HCC among patients treated with NUC treatment.

    “Our treatment-naive data suggests that the risks of HBV-related HCC are extremely low if the patients do not have significant fibrosis. This hypothesis was further supported by our on-treatment data that no HCC developed in NUC-treated patients FIB-4 [below] 1.29 … which suggest an early anti-viral therapy may minimize the HCC risk,” the researchers concluded.

    Tseng TC, et al. Am J Gastroenterol. 2017;doi:10.1038.ajg/2017.254.

    By Talitha Bennett

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    The availability of direct-acting antivirals is reducing disparities in the uptake of hepatitis C treatment http://www.eatg.org/news/the-availability-of-direct-acting-antivirals-is-reducing-disparities-in-the-uptake-of-hepatitis-c-treatment/ Wed, 30 Aug 2017 20:55:42 +0000 http://www.eatg.org/?post_type=news&p=6060 Improvement in treatment access for people with HIV co-infection

    An analysis from British Columbia, Canada shows that older people, individuals with HIV co-infection, people with cirrhosis and – to some extent – injecting drugs users have been significantly more likely to receive directly acting antiviral treatments, compared to the older interferon-based treatments. The findings show that in the current era, treatment uptake has improved for groups who tended not to receive interferon-based treatments, Naveed Janjua and colleagues write in the August issue of the Journal of Viral Hepatitis.

    However individuals living in economically deprived neighbourhoods remained significantly less likely to receive treatment, although healthcare is publicly funded and free of charge to patients in British Columbia.

    In the era of interferon-based treatments for hepatitis C, the rate of treatment uptake was low (below 15%) and especially so for certain population groups, including people living with HIV and people who inject drugs. Some of the barriers to treatment included increased side-effects and healthcare providers’ expectations of poor adherence. The availability of short course, highly effective and well-tolerated direct-acting antivirals (DAAs) could be expected to remove barriers and increase treatment rates.

    Data come from a cohort of all people reported as having hepatitis C in British Columbia between 1990 and 2013, with data on drug prescriptions up to 2015. A total of 11,886 people received treatment:

    • 86.4% received an interferon-based regimen, including people receiving telaprevir or boceprevir with peginterferon/ribavirin.
    • 3.8% received a combination of DAAs with ribavirin or peginterferon/ribavirin.
    • 9.8% received DAAs only (in most cases, ledipasvir/sofosbuvir).

    The main analysis compared individuals receiving DAAs only with individuals receiving older interferon-based regimens. In multivariable analysis, the odds of being treated were increased for people between 45 and 54 years (adjusted odds ratio 2.7, 95% confidence interval 1.7-4.4) and people over 55 years (aOR: 15.2, 95% CI: 9.5-24.2).

    People co-infected with HIV had three times the odds of receiving DAAs (aOR: 3.0, 95% CI: 2.3-3.8). To a lesser extent, the odds of receiving DAAs were also higher for those with cirrhosis (aOR: 1.8, 95% CI: 1.5-2.2) and diabetes (aOR: 1.3, 95% CI: 1.1-1.5).

    Similarly, those with a history of injection drug use had slightly higher odds of receiving DAAs (aOR: 1.3, 95% CI: 1.1-1.7), as did individuals on opioid substitution therapy (aOR: 1.3, 95% CI: 1.0-1.7).

    The authors note that these findings contrast with studies from other settings, in which people with a history of substance use were less likely to receive DAA treatment. Although research has shown good adherence and virological outcomes in people who inject drugs, clinicians and policy makers may be concerned about the potential for reinfection if a person continues to inject drugs. “Changes in the cost of treatment and developing treatment programs that reduce the risk of reinfection will be needed to overcome barriers to HCV treatment with DAAs among PWIDs,” they say.

    Finally, compared to patients from the most-privileged neighbourhoods, the odds of receiving DAAs were lower for patients in materially deprived neighbourhoods. Whereas the aOR for those in the second quintile was 1.0 (95% CI: 0.8-1.2), for those in the fifth quintile (the most deprived) it was 0.7 (95% CI: 0.6-0.9). This is despite free access to healthcare in British Columbia. The researchers call for interventions to reduce these inequalities.

    “These findings indicate an improvement in treatment uptake in the DAA era for population groups who were traditionally not treated with interferon-based treatments,” the authors conclude.

    By Roger Pebody

    Reference

    Janjua NZ et al. Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study. Journal of Viral Hepatitis 24: 624-630, 2017. (Abstract).

    ]]>
    Continuum of hepatitis C care in France: A 20-year cohort study http://www.eatg.org/news/continuum-of-hepatitis-c-care-in-france-a-20-year-cohort-study/ Wed, 30 Aug 2017 20:50:47 +0000 http://www.eatg.org/?post_type=news&p=6058 Abstract

    Background

    Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study.

    Methods

    We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment.

    Results

    In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4–2.9), age > 45 years (HR 1.5, 95%CI 1.02–2.3), patient acceptance of care (HR 9.3, 95%CI 5.4–16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4–16.0), and absence of cancer (HR 6.7, 95%CI 1.6–27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC.

    Conclusions

    Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.

    Read the full study here.

    ]]>
    Liver cancer risks not affected by hepatitis C eliminating therapy http://www.eatg.org/news/liver-cancer-risks-not-affected-by-hepatitis-c-eliminating-therapy/ Wed, 30 Aug 2017 20:46:47 +0000 http://www.eatg.org/?post_type=news&p=6057 Hepatitis C virus (HCV) patients faced a similar risk of developing liver cancer whether they eradicated the virus with direct-acting antiviral (DAA) drugs or interferon therapy, researchers in Japan found.

    Yuko Nagaoki and colleagues at Hiroshima University compared the occurrence of hepatocellular carcinoma (HCC) in HCV patients cured with DAAs and those given pegylated interferon with ribavirin (PEG-IFN/RBV). Treating chronic HCV is important because the virus is a leading cause of cirrhosis, liver failure and HCC.

    “The goal of chronic HCV infection treatment is eradication of the virus in order to prevent HCC development,” Nagaoki, an assistant professor at , and her team wrote in a paper regarding the study.

    Japan approved Bristol-Myers Squibb’s daclatasvir (Daklinza) and asunaprevir (Sunvepra) for genotype 1 HCV in 2014. About 95% of patients attained sustained virologic response (SVR) in real-world studies with the interferon-free DCV/ASV DAA treatment, previous research has shown.

    However, it was unknown whether this regimen would reduce a patient’s risk of developing HCC to the same extent as treatment with PEG-IFN/RBV, the researchers said.

    To investigate, the team assessed 398 HCV genotype 1 patients. All were treated at Hiroshima University Hospital and attained SVR from January 1995 to April 2015. Individuals who’d previously undergone HCV treatment or who had a history of HCC were excluded from the analysis.

    There were 154 patients in the interferon-free DCV/ASV group and 244 individuals in the PEG-IFN/RBV group. The DAA patients had a median age of 73, versus 59 for the interferon patients, and were mainly female (62.3% versus 52.2%). This group also had more complicating factors, including greater levels of diabetes, alcohol intake and hypertension. To overcome these covariates, one-to-one matches were created using propensity score analysis, the authors said.

    All patients were tracked for HCC at least biannually after the virus was eradicated.

    HCC was seen in 13 of the 244 (5.3%) PEG-IFN/RBV group members and 7 of the 154 (4.5%) individuals given DCV/ASV.

    The cumulative rates of HCC development at 1, 3 and 5 years were 0.4%, 3% and 5% for the PEG-IFN/RBV patients and 0.6%, 9% and 9% for the DCV/ASV group, respectively. Propensity score matching analysis showed similar rates of HCC development in the two groups, the researchers said.

    “In the present study, HCC development risk was similar between the PEG-IFN/RBV and the DCV/ASV groups in both patients with and without advanced liver fibrosis,” the researchers wrote.

    The researchers noted that a previous study had found that DAAs did not reduce the risk of HCC occurrence in patients with cirrhosis.

    “It is possible that HCV eradication by DAA therapy could enhance HCC development or recurrence in patients who have elevated risk for HCC,” they wrote. “However, the present study showed no evidence for an increase in HCC development following achievement of HCV eradication by DAA therapy.”

    The team said further analysis is needed to clarify the relationship between liver fibrosis and the risk of developing HCC after HCV is cleared with DAA drugs. They also suggested large-scale, long-term follow-ups to study patients treated with other direct-acting antiviral regimens.

    The study, “The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy,” was published online in the journal PLOS this month.

    By Gail Connor Roche

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    New WHO guidelines for hepatitis B virus vaccine http://www.eatg.org/news/new-who-guidelines-for-hepatitis-b-virus-vaccine/ Wed, 30 Aug 2017 20:42:30 +0000 http://www.eatg.org/?post_type=news&p=6056 The World Health Organization (WHO) issued updated recommendations for the use of the hepatitis B virus (HBV) vaccine, including a WHO report containing excerpts of the new recommendations that was published in Vaccine.1,2

    The WHO regularly publishes position papers to update guidelines on the use of vaccines for the prevention of internationally widespread and pandemic diseases, and especially vaccines that are implemented on a large-scale or nationwide basis.1

    In the position paper, the WHO continues to emphasize that “[a] comprehensive approach to eliminating HBV transmission must address prevention of infections acquired perinatally and during childhood, as well as prevention of infections acquired by adolescents and adults.” Including HBV vaccines in national immunization programs is central to achieving this mission.1

    HBV is most commonly transmitted in the perinatal period, so the HBV monovalent vaccine should be administered to all infants within 24 hours after birth. Although the HBV vaccine becomes progressively less effective within several days after birth, a late dose given after 7 days can still prevent mother-to-child transmission and should be administered if the infant has not received the early birth dose. Infants who are premature or have low birth weight should also receive the birth dose.1

    The WHO also outlined the recommended HBV vaccine schedule after the birth dose, consisting of a 3- or 4-dose schedule, with each dose separated by 4 weeks. The birth dose administered to premature and low birth weight do not count toward these series. Booster doses after completing the series are generally not recommended because of lack of supporting evidence. However, the WHO calls for studies that examine the long-term immunity provided by the vaccine and whether booster doses are necessary in certain subgroups.1

    In countries with moderate or low prevalence of HBV infection, the most important mode of HBV transmission is from an infected individual to an unvaccinated individual. Those who were born before the implementation of universal HBV vaccination in childhood should receive catch-up vaccination against HBV. Younger individuals should be prioritized for catch-up vaccination because they are at the greatest risk for chronic HBV infection.1

    Individuals who have the highest risk for HBV infection should be vaccinated. Examples of high-risk groups include patients who have diabetes or HIV or are solid organ transplant recipients. Patients with HIV should be immunized at the earliest opportunity to maximize the immune response to vaccination.1

    The WHO does not recommend routine serological testing before or after vaccination. However, it may be cost-effective to perform prevaccination testing where services are available, as doing so may help avoid unnecessary vaccination in patients who have adequate immunity against HBV.1

    The position paper also provides guidance on monitoring performance and outcome measures. The WHO recommends establishing administration of the birth dose within 24 hours (“timely delivery”) as a universal performance measure and measuring the effectiveness of vaccination programs by monitoring the prevalence of HBsAg in the population.1

    By Crystal Wong

    Reference

    1. World Health Organization. Hepatitis B vaccines: WHO position paper, July 2017 – Recommendations [published online July 22, 2017]. Vaccine. doi: 10.1016/j.vaccine.2017.07.046
    2. World Health Organization. Hepatitis B vaccines: WHO position paper – July 2017. Wkly Epidemiol Rec. 2017;92(27):369-392.
    ]]>
    HBV surface antibody reduces risk for reactivation during chemotherapy http://www.eatg.org/news/hbv-surface-antibody-reduces-risk-for-reactivation-during-chemotherapy/ Wed, 30 Aug 2017 20:37:38 +0000 http://www.eatg.org/?post_type=news&p=6055 In a recent meta-analysis of patients with resolved hepatitis B who underwent chemotherapy for hematological malignancies, the presence of positive antibodies to HBV surface antigen, or anti-HBs, was correlated with a decreased risk for viral reactivation in the absence of antiviral prophylaxis.

    “This finding supports the inclusion of anti-HBs in screening protocols prior to chemotherapy for hematological malignancy with antiviral prophylaxis for those who are anti-HBs-negative,” the researchers wrote.

    The researchers searched for studies published from 1965 to Mar. 1, 2016, in the MEDLINE, Web of Science, Cochrane Register of Controlled Trials and Scopus databases using terms for HBV, cancer chemotherapy and virus reactivation and included 20 original reports in their analysis.

    The reports comprised 11 prospective studies, eight retrospective studies and one randomized control trial that compared Baraclude (entecavir, Bristol-Myers Squibb) HBV prophylaxis prior to chemotherapy with entecavir therapy for HBV reactivation, totaling 1,713 patients with complete serology data. Only one study with 41 patients examined antiviral prophylaxis.

    The risk for HBV reactivation was 7.2% (95% CI, 5-10) in 1,672 patients who did not receive antiviral prophylaxis during chemotherapy, 10% (95% CI, 5.8-16) in 800 patients who received Rituxan (rituximab; Genentech, Biogen) chemotherapy, and 4% (95% CI, 2.2-6.3) in 580 patients who received nonrituximab chemotherapy. Among 1,142 patients with lymphoma, the risk for reactivation was 8% (95% CI, 4-11).

    For the 388 patients who were positive for antibodies to HBV core (anti-HBc) but negative for anti-HBs, the risk for reaction was 14% (95% CI, 9.4-19) compared with a 5% risk (95% CI, 3-7) in 1,284 patients with anti-HBs.

    Compared with patients who were negative for anti-HBs, the presence of anti-HBs significantly reduced reactivation (OR = 0.21; 95% CI, 0.14-0.32). Specifically, in 800 who received rituximab-only chemotherapy, patients with anti-HBs had a greater reduced reactivation than those without (OR = 0.19; 95% CI, 0.11-0.31). The researchers also observed significantly reduced reactivation in patients with lymphoma who had anti-HBs (OR = 0.18; 95% CI, 0.11-0.28).

    The researchers observed no heterogeneity among any of the studies.

    “Given the risk of reactivation associated with rituximab-based therapy, we are in agreement with current guidelines that recommend HBV antiviral prophylaxis in patients receiving rituximab-based regimens regardless of anti-HBs status,” the researchers concluded. “However, the management of patients with resolved HBV infection receiving nonrituximab-based chemotherapy regimens remains uncertain.”

    Paul S, et al. Hepatol. 2017;doi:10.1002/hep.29082.

    By Talitha Bennett

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    AAP recommends newborn hepatitis B vaccine by 24 hours of age http://www.eatg.org/news/aap-recommends-newborn-hepatitis-b-vaccine-by-24-hours-of-age/ Mon, 28 Aug 2017 21:30:53 +0000 http://www.eatg.org/?post_type=news&p=6005 New recommendations from the American Academy of Pediatrics (AAP) say medically stable newborns weighing 2000 g or more should receive their first dose of the hepatitis B vaccine within the first 24 hours of life.

    The AAP’s Committee on Infectious Diseases and Committee on Fetus and Newborn published the policy statement online August 28 in Pediatrics. It endorses October 2016 recommendations made by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). The 2016 recommendation updated previous recommendations from 2005, which allowed clinicians to wait until the first well-baby visit to administer the first dose.

    The new recommendation was made because “we have not eliminated perinatal transmission of hepatitis B in the United States, and up to 1000 new perinatal cases occur every year,” Karen Puopolo, MD, PhD, one of the statement authors, told Medscape Medical News.

    The high rates of opioid addiction in many parts of the country added a sense of urgency, said Dr Puopolo, associate professor of clinical pediatrics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. “It was one of many reasons this change was recommended. The [Centers for Disease Control and Prevention] has documented that in a few states, there has been an increase in adult cases of hepatitis B coincident with opioid abuse, and that does raise the concern that more women of childbearing age will acquire the virus, increasing the risk of perinatal transmission.”

    Vaccinating neonates against hepatitis B has been a standard recommendation “for years and years,” she added. “What is different in this statement is only that we are recommending it be administered before 24 hours of age.”

    Also, “we really urge families to do it. Before, the recommendation was at 24 hours or on discharge from the birth hospital, which meant some infants did not get the vaccination until they were 2 or 3 days old. Now we are saying we really think you should get it before you are 24 hours old, as long as your birth weight is greater than 2000 g and you are medically stable.”

    The recommendation states that if the mother is known to be positive for the hepatitis B surface antigen (HBsAg), the newborn should receive both the vaccine and the hepatitis B immune globulin within 12 hours of birth, regardless of birth weight. Infants born to women who are HBsAg-negative should receive the vaccine within 24 hours if their birth weight is 2000 g or more. If the mother is HBsAg-negative and her newborn weighs less than 2000 g at birth, the infant should be vaccinated at 1 month of age as part of universal routine prophylaxis or at hospital discharge, whichever comes first.

    When the mother’s HBsAg status is unknown, the infant should receive the vaccination within 12 hours of birth, regardless of weight. That should be followed by hepatitis B immune globulin administration within 7 days or hospital discharge (whichever comes first) for children with a birth weight of at least 2000 g, or within 12 hours if they have a birth weight less than 2000 g.

    With this immunization schedule, followed by completion of the infant hepatitis B immunization series, rates of perinatal infection range from 0.7% to 1.1%, the authors explain. The vaccine alone is 75% to 95% effective at preventing perinatal transmission if it is administered within 24 hours of birth.

    Perinatal hepatitis B infection is associated with a 25% increase in the risk for premature death from illnesses such as cirrhosis or hepatocellular carcinoma, Dr Puopolo told Medscape Medical News. “So the child has a lifelong increased risk of very serious disease. And all of that can be prevented with timely administration of the hepatitis B vaccine.”

    “What ACIP and the AAP are saying is that, for everybody, the best approach to eliminating all perinatally acquired hepatitis B in the United States is to routinely administer the vaccine to all infants before 24 hours of age. This gives us the advantage of dealing with cases where the mother’s hepatitis B status is not known at birth,” she added. “It also accounts for cases in which the mother has tested negative in error, or has acquired the virus after being tested.”

    For infants born to women whose hepatitis B status is positive or unknown, the birth dose of the vaccine provides a “critical safety net,” the authors write.

    The authors have disclosed no relevant financial relationships.

    Pediatrics. 2017;140:e20171870.

    By Norra MacReady

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    Shorter anti-HCV regimen effective in patients with or without cirrhosis http://www.eatg.org/news/shorter-anti-hcv-regimen-effective-in-patients-with-or-without-cirrhosis/ Wed, 23 Aug 2017 18:34:14 +0000 http://www.eatg.org/?post_type=news&p=5951 An eight-week regimen containing grazoprevir-ruzasvir-uprifosbuvir appears to be effective for treating hepatitis C virus (HCV) infection in patients with or without cirrhosis, according to findings from a pair of randomized phase 2 open-label trials.

    Dr. Edward J. Gane from Auckland Clinical Studies, in Auckland, New Zealand, and colleagues – in part A of the C-CREST-1 and C-CREST-2 trials – randomly assigned 240 patients with HCV genotype 1, 2 or 3 and without cirrhosis to receive an eight-week course of a daily three-drug combination:

    – grazoprevir 100 mg, plus

    – either elbasvir 50 mg or ruzasvir 60 mg, plus

    – either 300 mg or 450 mg of uprifosbuvir.

    The studies were funded by Merck and Co.

    Sustained virologic response rates 12 weeks after the end of therapy (SVR12) were 92% with both doses of the grazoprevir-ruzasvir-uprifosbuvir regimen and ranged from 85% to 88% (depending on uprifosbuvir dose) with grazoprevir-elbasvir-uprifosbuvir, according to one of the reports, both online August 9 in The Lancet Gastroenterology and Hepatology.

    All four regimens were well-tolerated.

    “These results support the selection of grazoprevir plus ruzasvir plus uprifosbuvir 450 mg as the regimen for further clinical investigation in broader populations,” the researchers conclude.

    Dr. Eric Lawitz from Texas Liver Institute at the University of Texas Health San Antonio and colleagues extended these findings in part B of C-CREST-1 and C-CREST-2. In this trial, 675 patients with HCV-1, -2, -3, -4 or -6, with or without cirrhosis, received eight, 12, or 16 weeks of grazoprevir-ruzasvir-uprifosbuvir 450 mg, with or without ribavirin.

    SVR12 rates with eight weeks of therapy were 93% in individuals with genotype 1a, 98% with genotype 1b, 86% with genotype 2 (without cirrhosis; patients with HCV-2 and cirrhosis received a longer course), 95% with genotype 3 (treatment naive, without cirrhosis) and 100% with genotypes 4 and 6.

    “We were surprised by the relatively lower efficacy of an 8-week duration of this regimen among those with genotype 2 infection,” Dr. Lawitz told Reuters Health by email. “However, extending therapy to 12 weeks overcame this effect.”

    SVR12 rates were generally higher among participants with or without cirrhosis who received 12 or 16 weeks of therapy.

    There were no documented virologic failures after week 12 of follow-up, although 10 participants who achieved SVR12 were lost to follow-up.

    As in part A of the study, treatment with this fixed-dose combination with or without ribavirin was generally well tolerated.

    “Results from the current studies support further investigation of grazoprevir, ruzasvir, and uprifosbuvir as a pan-genotypic regimen in individuals infected with HCV with and without cirrhosis, and suggest that this combination has the potential to provide a safe, single-duration regimen in most populations, including individuals with cirrhosis infected with genotype 3 who had previously received treatment with pegylated interferon and ribavirin,” the researchers conclude.

    “We await data from phase 3 to know how this regimen might impact the current treatment landscape,” Dr. Lawitz said. “We hope that this regimen will be able to give providers more options with regard to pan-genotypic regimens for the treatment of HCV.”

    Dr. Eleanor M. Wilson from the University of Maryland School of Medicine, Baltimore, who coauthored an accompanying comment in the journal, told Reuters Health by email, “The safety and efficacy data seem promising, but it’s still investigational, so not sure about its impact on the field of hepatitis C treatment yet.”

    “With the recent approvals of Vosevi and Mavyret, in addition to the previously available options, I think the overall take-away is that it’s fantastic that there are more hepatitis C treatment options for patients and providers,” she said. “It’s tremendous that previously so-called ‘difficult-to-treat patients’ including those with previous treatment experience, comorbid conditions like HIV or renal disease, and those with advanced fibrosis and cirrhosis now have a variety of safe and highly effective options to treat their hepatitis C.”

    “My area of expertise is in novel treatment approaches, including strategies to reduce the treatment duration in order to increase access and decrease treatment cost, as well as options for patients who haven’t successfully cleared HCV with first-line therapy (due to problems of adherence or viral resistance), and from that standpoint, it’s an exciting time to be a hepatitis C provider,” Dr. Wilson said.

    Dr. Mark Sulkowski, who directs the viral hepatitis center at Johns Hopkins University in Baltimore, told Reuters Health by email, “We currently have multiple outstanding HCV regimens for the treatment of all genotypes of hepatitis C, which typically include combinations of direct-acting antiviral inhibitors of HCV protein targets NS3 (protease), NS5A and NS5B (polymerase). While we have seen the regulatory approval of multiple inhibitors of the NS3 and NS5A proteins, to date, only one (nucleotide) inhibitor of the NS5B polymerase active site has been approved, sofosbuvir.”

    “The C-CREST-1 and -2 studies provide a phase 2 evaluation of another (nucleotide) analogue inhibitor of NS5B, uprifosbuvir,” said Dr. Sulkowski, who was not involved in the research. “Based on the results of these studies, uprifosbuvir appears to be poised to move to phase 3 studies, and if successful in phase 3 trials, this agent could become a valuable addition to the available drugs to treat hepatitis C.”

    Dr. Gane did not respond to a request for comment.

    Merck funded the trials and employed most of the authors.

    By Will Boggs

    SOURCE: http://bit.ly/2fRhHna, http://bit.ly/2fSnWXK and http://bit.ly/2fSIIXa

    Lancet Gastroenterol Hepatol 2017.

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    Liver fibrosis speeds up around the menopause in women with HIV and HCV co-infection http://www.eatg.org/news/liver-fibrosis-speeds-up-around-the-menopause-in-women-with-hiv-and-hcv-co-infection/ Wed, 23 Aug 2017 18:25:05 +0000 http://www.eatg.org/?post_type=news&p=5950 Menopause is associated with accelerated liver fibrosis in women with HIV and hepatitis C virus (HCV) co-infection, investigators from the United States report in the online edition of Clinical Infectious Diseases. The study showed that liver damage due to fibrosis – the build-up of scar tissue after cell death caused by HCV-related inflammation – begins to speed up as the menopause takes place.

    The researchers say that the findings have important clinical significance, suggesting that peri- and post-menopausal women should be prioritised as candidates for HCV therapy using direct-acting antiviral agents (DAAs) to avoid further liver damage.

    “We found that liver fibrosis rates…increased as women transitioned through menopause,” comment the authors. “Importantly, we employed a robust statistical approach to account for potential confounding effects of chronological aging, and evaluated reproductive stages by hormonal confirmation of ovarian reserve. Acceleration of hepatic fibrosis also began during peri-menopausal years, suggesting that women may be at increased risk of liver scarring earlier than suggested by prior data relying on self-reported menopausal age.”

    Up to 15% of people with HIV in the United States have co-infection with HCV, at least three times the HCV infection rate seen in the general population. Untreated HIV infection is associated with accelerated HCV-related liver fibrosis. Sex is also a risk factor for fibrosis progression, with men having higher rates than women. This is thought to be because of the protective effects of oestrogen in women, and higher rates of fibrosis have been observed in post-menopausal women.

    However, previous research exploring the impact of reproductive ageing on fibrosis progression has been limited by lack of adjustment for chronological ageing and an absence of longitudinal follow-up. Moreover, the relationship between oestrogen and fibrosis progression has not been assessed in HIV-positive women.

    Investigators from the Women Interagency HIV Study (WIHS) designed a study involving 405 women with HIV/HCV co-infection who were pre-menopausal at baseline. Progression of menopause and liver fibrosis were monitored longitudinally. To enable the investigators to robustly assess the relationship between reproductive ageing and the progression of liver fibrosis, data were also collected on chronological age, race, alcohol use, metabolic syndrome, HCV viral load and HIV-related factors (CD4 cell count, use of antiretroviral therapy [ART], viral load).

    Menopausal status was assessed using serial measures of anti-Müllerian hormone (AMH). The level of AMH indicates the reserve of eggs left in the ovaries. Pre-menopause was defined as the presence of detectable AMH; peri-menopause was defined as the period within five years of AMH becoming undetectable; post-menopause was more than five years after AMH loss.

    Fibrosis was assessed using two measures: APRI and FIB-4.The APRI and FIB-4 scales use levels of liver enzymes and platelets to calculate the extent of liver damage.

    Median age at baseline was 37 years, and average age at the onset of menopause was 49 years. The majority of women were Hispanic (58%). At the start of the study, 6% had fibrosis stage 3 or above, which increased during follow-up to 32% when assessed using FIB-4 and 20% using APRI. Only 6% of participants reported heavy alcohol use. Most were taking ART (88%), but only 23% received any kind of HCV therapy with just 2% treated with DAAs. Approximately a quarter of participants had a history of diabetes and 11% had ever been diagnosed with metabolic syndrome.

    Median follow-up was 9.1 years, and a fifth of women took some form of hormone replacement therapy during this period.

    After taking into account chronological age, the investigators found that fibrosis was accelerated during peri-menopause compared to pre-menopause using FIB-4 (0.12 units/year faster; 95% CI, 0.02-0.21; p = 0.001) and APRI (0.05- units/year after; 95% CI 0.002-0.09; p = 0.06). Faster fibrosis progression was also present post-menopause compared to pre-menopause, though the difference was short of statistical significance for both FIB-4 (p = 0.07) and APRI (p = 0.06).

    After adjustment for other potential confounders including Hispanic ethnicity, ART use and alcohol consumption, peri-menopause continued to be associated with accelerated fibrosis (0.10 FIB-4 units/year after vs pre-menopause; 95% CI, 0.008-0.20; p = 0.034).

    “The current study represents an important advance in our understanding of the effects of reproductive ageing on liver fibrosis by highlighting the accelerated fibrosis that begins as early as pre-menopausal years,” comment the researchers. “Using AMH as a gold standard measurement of ovarian reserve we were able to evaluate each woman’s fibrosis rate as she transitioned across reproductive stage.”

    The authors conclude that fibrosis progression in women with HIV/HCV co-infection accelerates with reproductive age, independent of chronological age. “Accelerated fibrosis began in peri-menopausal years, highlighting a previously unrecognized group of women at increased risk of progressive fibrosis and associated complications,” they note. “Similar analyses using serial measures of fibrosis should be conducted in non-HCV related liver diseases, including women without HIV infection, given potential implications of ovarian reserve on fibrosis progression in women with a broad spectrum of liver diseases.”

    By Michael Carter

    Reference

    Sarkar M et al. Reproductive aging and hepatic fibrosis progression in HIV/hepatitis C virus co-infected women. Clin Infect Dis, online edition, 2017.

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    Sharing injection paraphernalia does not lead to HCV transmission http://www.eatg.org/news/sharing-injection-paraphernalia-does-not-lead-to-hcv-transmission/ Wed, 23 Aug 2017 18:24:40 +0000 http://www.eatg.org/?post_type=news&p=5970 New findings suggest that sharing paraphernalia used to cook and prepare injection drugs does not directly lead to transmission of hepatitis C virus.

    According to Robert Heimer, PhD, professor of epidemiology and pharmacology at the Yale School of Public Health, and colleagues, this contrasts with past epidemiological studies that reported HCV incidence linked to sharing “cookers” and filters. Heimer said those studies were not clear on whether the results reflected the contamination of such paraphernalia or syringe-mediated contamination among people who inject drugs (PWID).

    Heimer and colleagues used lab studies to show that transmission occurs via the needles used in preparing and injecting drugs, not through shared paraphernalia. In light of their results, they said syringe access programs should not spend their limited resources on providing “cookers” and filters to PWID. Instead, Heimer and colleagues said they should focus on distributing more syringes with fixed needles, which are less apt to harbor infectious HCV than those with detachable needles.

    HCV is prevalent among PWID, reaching universal levels in some populations, according to Heimer and colleagues. Their experiments attempted to replicate a common scenario in which PWID share bags or balloons of drugs.

    “These findings suggest it may not be HCV in shared ‘cookers’ and filters that leads to transmission, but instead that this kind of sharing is a surrogate for situations in which HCV-discordant injectors share drugs,” Heimer and colleagues wrote in The Journal of Infectious Diseases.

    “In this scenario, injectors collectively prepare drugs. If a contaminated syringe was used to add water, dissolve and apportion the drug, then some of the contents of the contaminated syringe would pass through the ‘cooker’ and filter and into the syringe of the uninfected person. In such a case, the ‘cookers’ and filters may not even harbor infectious virus, and the distribution of clean ones and warnings about sharing them may have little or no impact on HCV incidence.”

    To replicate the real-world scenario in which an injector with HCV shares drugs with an HCV-uninfected person, Heimer and colleagues prepared syringes containing residual liquid contaminated with the virus and used them to simulate the preparation of the next injection, passing the contents through the “cookers” and filters used to prepare the injections and then introducing them into a second syringe. The contents of the syringes, “cookers” and filters were then entered into a microculture system for testing.

    In their experiments, Heimer and colleagues could not recover HCV from “cookers” regardless of input syringe type or “cooker” design — in the study, ridged or smooth caps resembling soda bottle tops were used. HCV was recovered in 15.4% of filters when detachable needles were used, compared with 1.4% when fixed needles were used. Recovery of HCV was higher when comparing detachable needles with fixed needles for residue in input syringes (73.8% vs 0%) and receptive syringes (93.8% vs. 45.7%).

    Heimer and colleagues said past findings linking HCV transmission to shared “cookers” and filters have led to syringe access programs providing clean “cookers” and filters to PWID, but no evidence exists showing that this intervention reduces HCV incidence. They said their results should lead to a rethinking of these policies.

    “At a minimum, our findings should compel programs that serve PWID 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 expanding scarce resources to provide supplies that will do little or nothing to prevent HCV transmission. Given the usual situation of limited financial resources facing syringe exchange and related harm-reduction programs, spending money on objects that can have little impact on disease transmission should come to be viewed as profligate.”

    Heimer R, et al. J Infect Dis. 2017;doi:10.1093/infdis/jix427.

    By Gerard Gallagher

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    Low-level hepatitis B viral load raises liver cancer risk http://www.eatg.org/news/low-level-hepatitis-b-viral-load-raises-liver-cancer-risk/ Wed, 23 Aug 2017 18:23:54 +0000 http://www.eatg.org/?post_type=news&p=5966 Low but detectable HBV DNA during antiviral therapy is associated with detrimental long-term outcomes.

    Having even a low level of hepatitis B virus (HBV) while on treatment with Baraclude (entecavir) increases the risk of liver cancer, according to a recent report in Hepatology. These findings suggest that low-level viral load is not harmless, but the best approach for managing it remains unclear.

    Over years or decades, chronic HBV infection can lead to serious liver disease, including cirrhosis and hepatocellular carcinoma (HCC), a type of primary liver cancer.

    The nucleoside/nucleotide analog antivirals Baraclude and Viread (tenofovir disoproxil fumarate), which are the current recommended first-line medications for hepatitis B, can suppress HBV replication over the long term, but they seldom lead to a cure. Effective antiviral therapy can slow, halt or even partially reverse liver disease progression, but people with hep B remain at risk for liver cancer, especially if they have developed cirrhosis.

    However, the implications of persistent or recurring low-level virus while on antiviral therapy are not well understood. It is not clear whether people with low but detectable viral load while on a single potent antiviral should switch therapy or add another drug.

    To address this question, Jung Hee Kim, MD, of Sungkyunkwan University School of Medicine in Seoul, and colleagues did a study of previously untreated people with hepatitis B who started Baraclude monotherapy (taken alone).

    This retrospective analysis included 875 chronic hepatitis B patients. Two thirds were men, and the mean age was 48 years. About half had cirrhosis when they started Baraclude.

    The researchers compared the HCC risk of patients who maintained virological response, defined as persistently undetectable HBV DNA, and those who experienced persistent or intermittent episodes of detectable but low-level viral load not exceeding 2,000 international units per milliliter.

    Most people (97.1 percent) achieved a complete virological response after starting Baraclude, defined as HBV DNA below 12 IU/mL. More than half of these (58.6 percent) maintained viral suppression during follow-up, but the rest sometimes had low-level detectable virus. People with high pretreatment viral load and those who were hepatitis B “e” antigen (HBeAg) positive were less likely to maintain viral suppression.

    Overall, 85 people (9.7 percent) were newly diagnosed with HCC over a median follow-up period of nearly five years. People with low-level viral load developed liver cancer nearly twice as often as those who maintained viral suppression (14.3 percent vs. 7.5 percent at five years, respectively).

    The difference in HCC risk was even greater when looking only at patients with liver cirrhosis (23.4 percent vs. 10.3 percent, respectively). However, the difference in HCC incidence rates (4.0 percent vs. 6.9 percent, respectively) was no longer statistically significant among people without cirrhosis, meaning it could have occurred by chance.

    Based on these findings, the study authors concluded that low-level HBV levels are “not benign.”

    As low-level virus is associated with a worse clinical outcome, these findings suggest that “active management that can further induce [maintained virological response] should be pursued” for people with low-level HBV DNA while on potent nucleoside/nucleotide analogs, especially for those with cirrhosis, according to the authors.

    However, they acknowledge that studies of switching treatment for patients with low-level virus have produced conflicting results. Some studies support staying on the same antiviral monotherapy while others favor changing to a different high-potency antiviral or adding a new potent drug to existing therapy.

    “More data that can guide clinical practice are needed,” they wrote. “Until such data are available, clinicians must evaluate adherence for patients with [low-level virus]. If adherence is not a concern, providers should discuss the risks and benefits of each treatment strategy (add-on, switching and continuing monotherapy) in everyday practice, and the treatment decisions should be individualized.”

    In addition, people with hepatitis B should continue to undergo liver cancer screening.

    In an accompanying editorial, Albert Min, MD, of the Icahn School of Medicine at Mount Sinai, wrote: “[W]e are once again reminded that in managing chronic hepatitis B patients, we should remain vigilant in continuing regular HCC surveillance indefinitely, regardless of whether undetectable HBV DNA levels and/or even loss of HBsAg have been achieved, particularly in patients with cirrhosis.”

    By Liz Highleyman

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    Men on PrEP & HIV-positive men are getting hepatitis C during sex—here’s why http://www.eatg.org/news/men-on-prep-hiv-positive-men-are-getting-hepatitis-c-during-sex-heres-why/ Mon, 21 Aug 2017 20:44:18 +0000 http://www.eatg.org/?post_type=news&p=5939 Hepatitis C is best known as an infection transmitted by blood, with most new cases of hepatitis C caused by sharing injection drug use equipment. But this dangerous infection, which can cause liver disease, also has a higher prevalence among men who have sex with men who are living with HIV. And, practitioners are more recently noticing cases of sexually transmitted hepatitis C among men taking PrEP. What is going on?

    A new hypothesis of how hepatitis C is transmitted during sex

    In 2016 and 2017, a team of researchers at the Icahn School of Medicine at Mount Sinai in New York published two research studies challenging the idea that blood needed to be present during sex for hepatitis C transmission to happen. Prior to that point, it was widely believed that only “traumatic” sex acts like fisting that produced blood put people at risk for hepatitis C.

    Their first study showed that about one third of HIV-positive men who have sex with men, with recent HCV infection, have hepatitis C virus in their semen.

    “About one-third to one-half of men with HCV shed HCV into their semen,” Daniel Fierer, MD, the lead investigator of the study explained to BETA. “And some men just don’t. The message is that if HCV is in someone’s semen, and the semen gets into a person’s rectum, that person may acquire hepatitis C.”

    In the journal article, Fierer and colleagues explain that because 10 to 20 HCV particles is enough to establish a parenteral infection, an average ejaculate (which might contain between 50 and 6630 international units (IU) of virus) could plausibly be enough to establish an infection. “These seemingly low HCV levels could play a significant role in sexual transmission of HCV when deposited into a rectum whose surface epithelial [skin] layer has been disrupted through anal intercourse,” they said.

    The results of this study explain how men who bottom without a condom might acquire hepatitis C. But what about when men top—are they at risk for acquiring hepatitis C if they top without a condom?

    “The other body fluid I thought was necessary to look at—because semen doesn’t explain all hepatitis C transmissions—is rectal fluid,” said Fierer. In a second study, his research team tested the rectal fluid of men living with hepatitis C to see if they could detect the virus.

    In a sample of 45 MSM who were co-infected with HIV and HCV, the researchers found that about half (47%) had detectable HCV in their rectal fluid. There was a positive correlation between HCV viral load in someone’s blood and HCV detectable in their rectal fluid, with about 80% of men with chronic blood levels of viremia shedding HCV into their rectal fluid.

    “Our data show that an inserted penis would be exposed to at least 2,300 IU HCV in rectal fluid for the duration of anal intercourse. Although the surface of the penis is dry epithelium composed of stratified squamous cells and therefore relatively impermeable to HCV when intact, in the setting of the continuous friction of intercourse, this magnitude of exposure could result in absorption of HCV,” the authors said.

    “This explains to me how sexual [HCV] transmission happens,” said Fierer. “It can get into rectal fluid, so if you have a penis or a toy that comes into contact with infected rectal fluid during group sex, and then goes into someone else’s rectum, transmission can happen. If infected semen gets in your rectum, you might get hepatitis C. Hepatitis C is not a ‘professional’ sexually transmitted agent. It’s not as easily transmitted during sex as say, chlamydia or gonorrhea. But HCV can certainly be transmitted during sex.”

    How do we know sexually transmitted hepatitis C is happening?

    Finding out how often HCV transmission happens during sex can be difficult in the “real world,” when people are not tested for HCV regularly, or when researchers rely on self-report to find out if an HCV infection may have happened during injection drug use. There have been reports from clinicians around the world, however, documenting the sexual transmission of HCV.

    “We are seeing cases of hepatitis C at Dean Street who report no risk factors other than anal sex,” said Sheena McCormack, MBBS, MSc, FRCP, an HIV and sexual health clinician based at the London clinic 56 Dean Street. “Incidence is difficult to measure even amongst the PROUD participants who we are seeing and testing regularly as testing practices have changed over time. We were testing HIV-positive individuals who did not report additional risk factors more frequently than HIV-negative attendees but are now testing both populations. My estimate of incidence is 1-2% per year,” she told BETA.

    Among HIV-positive men attending a sexually transmitted infection clinic in Amsterdam, one study found that the prevalence of HCV increased from 5.6% in 1995 to 10.3% in 2010. This sample did include people who used injection drugs, although only a relatively small percentage of people (11%) reported this as a transmission risk (unprotected anal sex and fisting were separately found to be risk factors for HCV, giving evidence to support sexual transmission of HCV in this population).

    In San Francisco, researchers at the Department of Public Health have reported rates of HCV among HIV-positive men who have sex with men (who do not use injection drugs) ranging from 4.5% (in 2008) to 12.3% (in 2011). “It is of note that among HIV-infected non-IDU men, HCV prevalence is more than 8 times higher than among the general population in the United States,” explained Raymond Fisher, DrPH, the lead author of the study.

    Sexual transmission of hepatitis C to men on PrEP

    Sexual transmission of hepatitis C has also been noted among HIV-negative men who have sex with men on PrEP.

    In 2015, practitioners at Kaiser Permanente San Francisco Medical Center published a short report in Clinical Infectious Diseases describing two sexually transmitted hepatitis C cases found among 485 men who have sex with men receiving PrEP at the clinic.

    The first case was in a 46-year old man who started PrEP in 2013, who reported two cases of syphilis, rectal gonorrhea and rectal chlamydia from August 2013 to July 2014 and condomless receptive anal sex during that time. The second case was in a 37-year old man who started PrEP in 2013 who also acquired rectal chlamydia, rectal gonorrhea and syphilis between 2013 and 2014, and reported condomless anal sex during that time.

    “In both cases, no risk factors for HCV infection were reported other than sexual intercourse without condom use,” said Volk and colleagues. “These incident HCV infections suggest an important role for ongoing HCV monitoring for HIV-uninfected MSM receiving PrEP given the potential for sexual transmission in this population.”

    Fierer offered anecdotal evidence of hepatitis C transmission among men using PrEP.

    “I have seen 10 hepatitis C infections among men on PrEP in the last couple of years,” he said. “And these are men who do not use injection drugs so we can be reasonably certain they acquired hepatitis C sexually.”

    Are men living with HIV at higher risk?

    Rates of sexually transmitted hepatitis C are certainly higher among HIV-positive men who have sex with men than HIV-negative men who have sex with men, although it’s difficult to prove exactly why.

    Fierer reasoned that more men living with HIV end up getting HCV through sex because HIV is much more efficient at transmission through sex—which means that people at risk for getting HCV through sex are more likely to be those who have already been exposed to (and acquired) HIV.

    “If an HIV-negative man is at risk for acquiring hepatitis C through sex, that means he also might be at risk for acquiring HIV through sex. Chances are, he’s going to become infected with HIV first, which is why these cases of hepatitis C appear as though they’re largely affecting HIV-positive men,” he said.

    The question is, with PrEP breaking down barriers between HIV-negative and HIV-positive men, will the number of hepatitis C infections among HIV-negative men start to rise?

    “That’s what I’ve been saying,” said Fierer. “We are going to see more cases of sexually transmitted hepatitis C with increased use of PrEP. I don’t have a prospective cohort to prove it, but it’s biological. The sun rises, the sun sets, and infectious diseases are transmitted.”

    Sexually transmitted infections and hepatitis C

    New research, presented at the IAS 2017 conference in July, and published recently in BMC Infectious Diseases, shows for the first time that syphilis—but not chlamydia—also increases risk of sexually acquired hepatitis C infection.

    This is an important finding, said Nicholas Medland, MBBS and colleagues, because it brings to light a new biological pathway that may increase risk of hepatitis C. Syphilis can cause ulcers in the mucosal surfaces of the rectum, which may heighten susceptibility for hepatitis C infection if a person is exposed to HCV during anal sex. (Chlamydia typically does not cause these types of ulcers, which is why the researchers think this infection was not associated with increased hepatitis C risk.)

    “We wondered, why is it that some people get sexually transmitted hepatitis C and others don’t? Is it something about people’s sexual behavior? Or something about their bodies? So we looked at the risk factors for hepatitis C in our study,” said Medland.

    The study included data from 822 men living with HIV attending the Melbourne Sexual Health Centre (MSHC) in the Australian state of Victoria. All of the participants were receiving HIV care at the clinic, had two or more HCV antibody tests between January 2008 and March 2016 (with the first HCV test being negative) and had sexual contact with men as their first recorded risk factor for HIV acquisition. People were not included in the study if they used injection drugs (which is a separate risk factor for HCV).

    The rate of new syphilis diagnoses among the men included in the study increased more than three times during the study, which lasted between 2008 and 2016.

    “We found that if you got syphilis, this raised a person’s risk for getting sexually transmissible hepatitis C by about four times,” said Medland. “The overall incidence rate for hepatitis C was just over 1%, but if a person got syphilis it was closer to 5%. This is enough to warrant increased HCV testing, I think.”

    By Emily Newman

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    Health Canada approves Vosevi and Maviret for the treatment of hepatitis C http://www.eatg.org/news/health-canada-approves-vosevi-and-maviret-for-the-treatment-of-hepatitis-c/ Sun, 20 Aug 2017 21:23:42 +0000 http://www.eatg.org/?post_type=news&p=5928 Gilead Sciences Canada’s press release for the approval of Vosevi is available here.

    AbbVie Canada’s press release for the approval of Maviret is available here.

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    Medivir licenses exclusive rights to MIV-802 for Greater China to Ascletis http://www.eatg.org/news/medivir-licenses-exclusive-rights-to-miv-802-for-greater-china-to-ascletis/ Sun, 20 Aug 2017 19:30:31 +0000 http://www.eatg.org/?post_type=news&p=5931 Stockholm, Sweden and Hangzhou, China, 18 August 2017 — Medivir AB and Ascletis today announce that Ascletis has licensed the exclusive rights to develop, manufacture and commercialize Medivir’s nucleotide polymerase inhibitor for hepatitis C, MIV-802 (Ascletis code: ASC21), in Greater China.

    Under the terms of the agreement, Medivir received an upfront payment, and is entitled to receive milestones based on successful development through commercial launch and tiered royalties on net sales of MIV-802 containing products. Ascletis will fund clinical development, manufacturing and commercialization of MIV-802 in Greater China.

    “We are pleased to have Ascletis as a partner with their track record in advancing development of pharmaceuticals in Greater China and their portfolio of antivirals with which to create a combination drug against hepatitis C” said Christine Lind, CEO of Medivir.

    “Ascletis has filed an NDA in China for its first HCV NS3/4A medicine, danoprevir, at the end of 2016 and has an HCV NS5A inhibitor in the late stage clinical development. By acquiring MIV-802, a nucleotide NS5B inhibitor, Asceltis is committed to treating, eventually eliminating, hepatitis C in greater China with its multiple leading antiviral combinations including MIV-802,” said Dr. Jinzi J. Wu, CEO of Ascletis.

    About MIV-802

    MIV-802 is a potent, pangenotypic nucleotide inhibitor of the HCV NS5B polymerase. Hepatitis C treatments comprise combinations of pharmaceuticals with different antiviral mechanisms. Preclinical data indicate that MIV-802 can be used effectively in combination with other classes of antiviral agents for the treatment of HCV, including protease inhibitors, non-nucleoside NS5B inhibitors, and NS5A inhibitors.

    About Medivir

    Medivir is a research-based pharmaceutical company with a focus on oncology. We have a leading competence within protease inhibitor design and nucleotide/nucleoside science and we are dedicated to develop innovative pharmaceuticals that meet great unmet medical needs. Medivir is listed on the Nasdaq Stockholm Mid Cap List.

    About Ascletis

    Ascletis is a leading biotechnology company dedicated to discovering, developing and commercializing new treatments for liver diseases. Ascletis has assembled an entrepreneurial management and senior scientific team with a track record of successful pharmaceutical discovery and development at major global pharmaceutical companies. To date the company has added four late-stage candidates to its product portfolio: Danoprevir (ASC08), an NDA-filed HCV protease inhibitor, licensed from Roche; Ravidasvir (ASC16), phase II completed HCV NS5A inhibitor, licensed from Presidio Pharmaceuticals; ASC06, a clinical stage, first-in-class, RNAi therapeutic for the treatment of liver cancers, licensed from Alnylam Pharmaceuticals; and ASC09, a phase IIa completed HIV protease inhibitor, licensed from Janssen, a Johnson & Johnson company.
    For more information, please visit www.ascletis.com or www.ascletis.com.cn

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    Serum viral load predicts HBV flares in patients who cease therapy http://www.eatg.org/news/serum-viral-load-predicts-hbv-flares-in-patients-who-cease-therapy/ Sun, 20 Aug 2017 19:28:24 +0000 http://www.eatg.org/?post_type=news&p=5929 Persistent or severe hepatitis followed virological relapse among patients who discontinued treatment with Baraclude for chronic hepatitis B, according to recently published data. Serum viral load at treatment cessation predicted clinical flares.

    “It remains controversial whether [chronic hepatitis B] patients can safely discontinue [nucleos(t)ide analogues] before HBsAg loss. How to predict durable off-therapy remission has become the focus of intense research,” the researchers wrote. “Our study adds to current understanding about the risk and risk stratification of clinical hepatitis subsequent to virological relapse in [chronic HBV] patients who stop taking [Baraclude].”

    The prospective study comprised 92 patients diagnosed with chronic HBV for more than 6 months, had been treated with Baraclude (entecavir, Bristol-Myers Squibb) for a minimum of 3 years, and were seronegative for both HBeAg and viral DNA at treatment cessation. The patients developed virological relapse over a mean follow-up of 12.6 months.

    Fifty-two patients encountered clinical hepatitis with a cumulative incidence of 61% (95% CI, 49.9-72.3) at 2 years from treatment cessation and 37 patients developed persistent or severe hepatitis with a cumulative incidence of 53% (95% CI, 40.9-66.2) at 2 years.

    The researchers found that serum viral load at the time of virological relapse was a significant risk factor for clinical hepatitis after adjusting for alanine aminotransferase (ALT; HR = 1.31 per log IU/mL; 95% CI, 1.07-1.6). They also observed that severity of viremia at relapse was an independent risk factor for subsequent persistent or severe hepatitis (HR = 1.63 per log IU/mL; 95% CI, 1.27-2.1), after adjusting for the effect of ALT at relapse and alpha-fetoprotein at treatment cessation.

    The risk for both clinical hepatitis and persistent or severe hepatitis increased incrementally with serum viral load in a dose-dependent manner (P < .0001). Patients with HBV DNA higher than 100,000 IU/mL at virological relapse had a 2-year cumulative incidence of 89.7% (95% CI, 72.4-89.2) for clinical hepatitis compared with 51.3% (95% CI, 38.6-65.5) in those with viremia lower than 100,000 IU/mL.

    Patients with viral load higher than 100,000 IU/mL similarly had a higher risk for developing persistent or severe hepatitis at a cumulative incidence of 88% (95% CI, 69.7-97.9) compared with 41.7% in those with a viral load less than 100,000 IU/mL (95% CI, 28.2-58.2).

    “The major concern of stopping [nucleos(t)ide analogue] in [chronic HBV] patients is the risk of acute on chronic liver failure that may rapidly ensue after a severe bout of clinical flare,” the researchers wrote. “Based on our findings, retreatment should not be deferred in patients who relapse with a high viral load. Identification of this indicator helps to diminish the risk of persistent or severe clinical hepatitis.”

    Hsu YC, et al. J Gastroenterol Hepatol. 2017;doi:10.1111/jgh.13728.

    By Talitha Bennett

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    Experts and patients come together on people-centred hepatitis response in the Russian Federation http://www.eatg.org/news/experts-and-patients-come-together-on-people-centred-hepatitis-response-in-the-russian-federation/ Thu, 17 Aug 2017 21:36:59 +0000 http://www.eatg.org/?post_type=news&p=5913

    Awareness is growing in the Russian Federation on the need for a strategy on viral hepatitis. Patients and doctors are pointing to the huge burden of disease and the challenges in accessing health services. WHO is advocating for action based on the global and European strategy and plan.

    On 25 July 2017, patients, doctors, experts, civil society and WHO/Europe came together in a round-table discussion in Moscow dedicated to World Hepatitis Day. They discussed building the Russian viral hepatitis response based on the voices of experts and patients, so as to make it both sound and centred on the needs of the people affected.

    The huge burden of disease from viral hepatitis

    Dr Irina Shestakova, Chief Specialist on Infectious Diseases of the Ministry of Healthcare of the Russian Federation, stated, “Around 16% of all deaths in the Russian Federation were due to viral hepatitis-related liver disease in 2016. That is three times more than deaths from road traffic”.

    Leading clinicians and representatives of patients’ organizations presented and debated the epidemiological situation and response to viral hepatitis. This discussion included the challenges in accessing laboratory diagnosis, as well as the modern and highly effective treatment for chronic hepatitis in the country.

    Participants were joined via video conference by representatives from the leading international hepatitis patients’ organizations: the World Hepatitis Alliance and European Liver Patients’ Association. They discussed the value of a national strategy that would guide the Russian Federation’s response to its hepatitis epidemic, and contribute to achieving the global elimination goal by 2030.

    Global goal: elimination of hepatitis by 2030

    The Russian initiative takes place within the global and European frameworks.

    • The first-ever “Global health sector strategy on viral hepatitis”, adopted in May 2016 by the World Health Assembly, calls for the elimination of viral hepatitis as a public health threat by 2030.
    • The “Action plan for the health sector response to viral hepatitis in the WHO European Region”, adopted in the same year, identifies priority actions to achieve this goal in the Region.

    Similarly, many other countries are developing national strategies or action plans and strengthening their response. WHO assists them with guidelines and operational manuals and by providing technical assistance on request.


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    Treatment with DAAs reduces the risk of mortality in the first 18 months after the completion of treatment http://www.eatg.org/news/treatment-with-daas-reduces-the-risk-of-mortality-in-the-first-18-months-after-the-completion-of-treatment/ Tue, 15 Aug 2017 17:33:38 +0000 http://www.eatg.org/?post_type=news&p=5872

    For the first time, a large study has demonstrated that treatment with direct-acting antivirals (DAAs) significantly reduces mortality rates among people with hepatitis C virus (HCV) monoinfection. The study – published in Clinical Infectious Diseases – matched people who received therapy with all-DAA regimens with untreated controls. Mortality rates in the first 18 months after therapy were significantly lower among individuals who received DAAs. After controlling for other factors, treatment with DAAs was associated with a 57% reduction in the risk of death.

    “To our knowledge, this is the first large-scale study to demonstrate the effect of newer DAA regimens upon survival,” write the authors. “Treatment with 2 commonly used DAA regimens…was associated with significant improvements in survival within the first 18 months of treatment, compared with demographically and clinically similar untreated HCV-infected controls.”

    DAAs have revolutionised the treatment of people with HCV, with all-oral regimens achieving sustained virologic response (SVR) – or cure – rates in excess of 90% in clinical trials. Successful treatment with DAAs in routine care has already been shown to be associated with a lower risk of fibrosis progression. However, the survival benefit from successful DAA therapy has never been examined in a large study.

    A recent Cochrane Collaboration systematic review concluded that, due to the lack of long-term follow-up studies, there was no evidence that DAAs prolonged life or reduced liver-related ill-health in people who achieved SVR to DAA treatment. The Cochrane review has been strongly criticised by European and United States associations of liver experts for ignoring the short-term nature of the studies of DAAs designed for registration and for ignoring previous evidence from the treatment of hepatitis C, which showed that achieving SVR to interferon-based treatment was associated with a reduction in the risk of death and liver disease.

    Investigators from the ERCHIVES (US Electronically Retrieved Cohort of HCV Infected Veterans) study compared survival between people treated with one of two all-DAA regimens – paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) – and matched HCV-infected untreated controls.

    Individuals with HIV, hepatitis B virus and liver cancer were excluded from the study, as were people without baseline HCV viral load measurements or FIB-4 measurements of liver disease.

    The study populations consisted of 6970 people treated for at least 14 days (5497 of whom received LDV/SOF) and an equal number of untreated HCV-infected controls.

    Median age was approximately 61 years and approximately 96% of individuals were male. Ninety-four per cent of those treated with LDV/SOF and 90% of those treated with PrOD achieved SVR.

    There were some significant differences between the treated individuals and the controls. Those receiving DAAs were more likely to be obese and have liver cirrhosis, but less likely to have serious kidney disease, drug or alcohol dependence and anaemia.

    In the first 18 months of follow-up, mortality was significantly higher (p < 0.001) among the untreated controls (2.5%) compared to either treatment group (PrOD,  0.3%; LDV/SOF, 1.4%).

    Treatment with either regimen was associated with a 57% reduction in mortality (HR = 0.43%; 95% CI, 0.33-0.57). Comparison between individuals who received therapy showed that attainment of an SVR was associated with a 43% reduction in the risk of mortality (HR = 0.57; 95% CI, 0.33-0.99).

    Between 17 and 20% of treated people had a history of drug or alcohol abuse. This was not associated with lower chances of survival. “Our results suggest that a history of these conditions should not deter providers from initiating treatment,” comment the investigators.

    “Treatment for HCV with either PrOD or LDV/SOF and attainment of SVR are associated with a significant reduction in mortality, a benefit that is seen within the first 18 months of treatment,” the authors conclude. “Benefits of treatment at a population level are expected to be substantial.”

    By Michael Carter

    References

    Butt, AA et al. Effect of paritaprevir/ritonavir/ombitasvir/dasabuvir and ledipasvir/sofosbuvir regimens on survival compared with untreated hepatitis C virus-infected persons: results from ERCHIVES. Clin Infect Dis, online edition. DOI.10.1093/cid/cix364.

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