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02 Oct 2020

The evolution and clinical impact of hepatitis B virus genome diversity

Authors:

Professor Peter Revill, Dr Thomas Tu (Westmead Institute for Medical Research), Professor Hans Netter, Dr Lilly Yuen, Professor Stephen Locarnini and Dr Margaret Littlejohn.

Doherty Institute researchers have recently published an invited review in the prestigious journal Nature Reviews Gastroenterology and Hepatology, providing insights into the evolution of hepatitis B virus (HBV) and discussing how HBV (and hepatitis delta virus) genetic variants and mutants are believed to play a role in disease progression and treatment response. 

HBV infection remains a global public health issue, with 257 million people chronically infected, resulting in more than 880,000 deaths per year worldwide. Although there is an effective preventive vaccine, there is no cure for chronic hepatitis B, current therapies can stop the virus from replicating, but cannot get rid of it. Nor do they eliminate the risk of HBV-mediated liver cancer.

The team’s review discusses HBV origins and evolution, as an ancient virus with deep ancestry in the animal kingdom. This is timely as a number of recent reports have greatly extended the host range of HBV related viruses (including fish and bats!), as well showing that HBV related viruses have been around for millions, rather than thousands of years as previously suggested.

It looks at the importance of HBV diversity in the HBV replication cycle and the mechanisms by which it occurs, both within an individual during infection, and at a population level. These mechanisms include features of the unique HBV replication cycle, as well as different selection pressures that are imposed by the immune system of the infected person. Chronic hepatitis B is not a ‘one size fits all’ disease, with HBV diversity contributing to the marked variations in HBV natural history, disease progression and treatment response observed in those living with chronic infection across the globe.

Enhancing our understanding of HBV diversity is key to optimising the use of current therapies, providing insights into disease prognosis, and stratifying patients for trials of new therapeutic interventions. HBV viral diversity must also be considered in the development of new treatments to ensure they are effective against different HBV variants.

Viral hepatitis is a global public health problem, and the burden of disease is increasing. In 2016, spurred by development of effective new curative treatments for hepatitis C and expanding access to hepatitis B vaccination, the 194 Member States of the WHO committed to eliminating viral hepatitis as a public health threat by 2030. This review contributes to this admirable goal, forming part of an important series of articles detailing what will be required to eliminate viral hepatitis as a public health threat by 2030.

This work was a collaboration between the Doherty Institute and Westmead Institute for Medical Research.

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