EATG » Hepatitis B: Search for the cure and challenges that remain

Hepatitis B: Search for the cure and challenges that remain

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.
Share on FacebookTweet about this on TwitterShare on Google+Pin on PinterestShare on LinkedIn
Source:
Infectious Disease Advisor
News categories: Hepatitis