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Global drive for hepatitis B cure launched at International Liver Congress

Keith Alcorn
10 April 2019

The Global Scientific Strategy to Cure Hepatitis B (The ICE-HBV Strategy) by the International Coalition to Eliminate HBV (ICE-HBV), a global group of researchers, patient representatives and health organisations, was released on the opening day of The International Liver Congress in Vienna.

Over 257 million people worldwide are living with chronic hepatitis B infection and over 887,000 die due to the infection each year. Chronic hepatitis B causes almost 40% of hepatocellular carcinoma, which is the second leading cause of cancer-related mortality worldwide.

Hepatitis B infection cannot be cured with current treatments because viral DNA persists in liver cells even when virus production is suppressed by antiviral treatment. The virus also causes permanent changes in liver cells that increase the risk of developing hepatocellular carcinoma even when the hepatitis B virus (HBV) is fully suppressed.

As in the case of HIV, scientists are pursuing two approaches to curing hepatitis B infection. One approach is to aim for a sterilising cure, defined as complete elimination of hepatitis B cccDNA (covalently closed circular DNA) and integrated DNA from liver cells and undetectable hepatitis B surface antigen (HBsAg) in the blood. The other approach is to achieve a functional cure, defined broadly as undetectable HBsAg or HBV DNA in blood after discontinuation of antiviral treatment.

Researchers say that a functional cure seems more achievable and point to the experience of millions of people who clear acute hepatitis B infection through a strong immune response within months of exposure. Around 90% of adults exposed to hepatitis B clear acute infection but may have a small reservoir of hepatitis B-infected cells in the liver. Understanding how immune system control of hepatitis B can be promoted in people with chronic infection without the need for lifelong treatment is one aim of the ICE-HBV Strategy.

In the longer term, scientists need to understand how to measure HBV cccDNA in cells, how HBV cccDNA interacts with host cells in the liver and which are the most promising targets to interfere with the cccDNA lifecycle to reduce levels in liver cells. They also want to understand other critical steps in the HBV lifecycle, as combination therapies like those used to cure hepatitis C and suppress HIV will probably be needed to control or eliminate HBV.

“Curing hepatitis B is not a pipe dream,” said Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, Australia. “While the pharmaceutical industry will develop novel drugs and evaluate them in clinical trials, we have an ethical and scientific imperative to foster collaborations with clinical scientists outside of industry if we are to see successful drug development, the facilitation of clinical studies, the characterizing correlates of “cure”, refining treatment endpoints and identifying the best patients for clinical trials according to the mode of action (MoA) of the tested drugs. The ICE-HBV Global Scientific Strategy can help make that happen and get us on the road towards an HBV cure.”

ICE-HBV consists of international scientific working groups that bring together leaders in HBV virology, immunology, technology and clinical research, who have worked to identify research priorities to achieve a safe, scalable and affordable cure for hepatitis B infection.