Maintenance Mechanism of Chronic HBV Infection and the Strategy for Functional Cure

Chronic Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis (LC), liver failure (LF) and hepatocellular carcinoma (HCC) in China. In addition to a 3.2 kb partially double-stranded relaxed circular DNA (rcDNA) genome, the HBV DNA exists in two other forms, covalently closed circular DNA (cccDNA) serves as the source of HBV replication and its persistence sustains chronic HBV infection, while integrated HBV DNA (iDNA) can continuously express surface antigen (HBsAg) independently of the viral life cycle. Following cccDNA clearance or transcriptional silencing, iDNAs becomes the primary source of serum HBsAg. Thus, in the future, there is an urgent need to develop drugs that can more effectively inhibit viral replication, accelerate the depletion/silencing of cccDNA as well as iDNA, and specifically enhance the host immunity against HBV with fewer side effects to achieve the functional cure of CHB. This review analyzes the mechanism sustaining chronic HBV infection through virus-immune interaction and examines recent clinical studies on CHB treatment and potential cure strategies.