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Finding a cure for hepatitis B: are we close?

Hepatitis B virus (HBV) takes a huge human and economic toll. Despite this, research into HBV is drastically underfunded, to the point that it was recently compared to a neglected tropical disease. But hope for a cure is growing.

A computer-generated image of the hepatitis B virus
Jason Roberts, Doherty Institute

Causing more than 887 000 deaths each year, HBV is a major threat to global public health. Some 257 million people worldwide are chronically infected with HBV, and the disease causes around 40% of all primary liver cancers – the second most deadly cancer.

In 2016, global partners joined forces to create the International Coalition to Eliminate Hepatitis B (ICE-HBV), with the aim of fast-tracking the discovery of a cure for HBV. The ICE-HBV formed international working groups comprising more than 50 global scientific leaders in HBV virology, immunology, technology and clinical research. The fruits of this partnership are now starting to show.

At the International Liver Congress (ILC) in Paris in April 2018, ICE-HBV members reported on encouraging developments towards an HBV cure. There are now almost 50 new anti-HBV and hepatitis D virus treatments being openly investigated, and 17 of these are already undergoing phase II clinical trials.

While a vaccine to prevent HBV exists, lifelong treatment is needed for those already chronically infected. Treatment helps keep HBV under control, but it is not a cure because it cannot completely clear HBV from infected cells. In addition, even with ongoing treatment, people are still at a higher risk of developing liver cancer, particularly those with underlying cirrhosis due to chronic HBV.

Recent scientific progress – and the momentum created by the discovery of a cure for hepatitis C virus (HCV) – has created a sense of renewed hope, as well as increased pressure, to find a cure for HBV, which affects more people and has a higher death rate than HCV.

Pre-clinical studies in animals also presented at ILC 2018 revealed that the most promising strategies are based on a combination of antiviral approaches that target both the virus itself (direct acting) and the human cells that host the virus (indirect acting). Indeed, getting HBV to stop replicating seems necessary, but it isn’t enough to stop the virus returning after treatment is discontinued.

In mice, effective new direct antivirals targeting the virus, combined with a therapeutic vaccination that aims to eliminate the virus, followed by immune boosting, gave promising results towards achieving a HBV “functional cure” – i.e. where HBV is reduced to permanently harmless levels after stopping treatment, but some residual virus may still be present in the body.

However, none of the approaches have so far had an effect on reaching the viral reservoir in the liver – this remains a major objective for future strategies.

While it is not possible to give a precise timeline, hope of finding an HBV cure is strong, and the scientific community – academic and industry alike – are clearly racing in the right direction.

source: who.int