Biology of hepatitis B virus DNA integration and its impact on antiviral R&D

Hepatitis B virus (HBV) drastically increases the risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) in the ∼300 million people with chronic hepatitis B infections. HBV reproduces through an epigenetic circular genome, but can occasionally integrate into the host genome as a replication-defective form. These integrated forms have been reported to contribute to virus persistence and hepatocarcinogenesis. In this review, we highlight the effects of current and novel treatment under development on HBV DNA integrations and provide areas of potential research to develop more effective therapies that target the underlying drivers of persistence and pathogenesis.