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
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
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.
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.