Abstract
Chronic hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma, estimated to be globally responsible for ∼800,000 deaths annually. Although effective vaccines are available to prevent new HBV infection, treatment of existing chronic hepatitis B (CHB) is limited, as the current standard-of-care antiviral drugs can only suppress viral replication without achieving cure. In 2016, the World Health Organization called for the elimination of viral hepatitis as a global public health threat by 2030. The United States and other nations are working to meet this ambitious goal by developing strategies to cure CHB, as well as prevent HBV transmission. This review considers recent research progress in understanding HBV pathobiology and development of therapeutics for the cure of CHB, which is necessary for elimination of hepatitis B by 2030.
Highlights
Hepatitis B virus (HBV) is a small hepatotropic DNA virus that can persist and lead to chronic necro-inflammatory liver diseases
The long-term suppression of viral replication by NUCs reduces the risk of death due to liver diseases by 50% to 70% [3,4,5], viremia recurs following treatment cessation and fewer than 5% to 15% of those treated achieve the loss of circulating HBV surface antigen (HBsAg) [6, 7], which is an important marker of functional Chronic hepatitis B (CHB) cure [8]
HBV is a member of the Hepadnaviridae family and has a 3.2-kb, partially double-stranded, relaxed circular DNA genome in an icosahedral capsid enveloped with a lipid bilayer studded with three viral envelope proteins [11]
Summary
Hepatitis B virus (HBV) is a small hepatotropic DNA virus that can persist and lead to chronic necro-inflammatory liver diseases. The long-term suppression of viral replication by NUCs reduces the risk of death due to liver diseases by 50% to 70% [3,4,5], viremia recurs following treatment cessation and fewer than 5% to 15% of those treated achieve the loss of circulating HBV surface antigen (HBsAg) [6, 7], which is an important marker of functional CHB cure [8]. Optimism that the goal of elimination might be possible has increased because of public health outreach advances and an improved understanding of HBV replication and immunopathogenesis that is enabling the development of novel therapeutics. These advances are discussed in this review
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