Emerging antiviral drugs and immunotherapy for chronic hepatitis B and associated liver disease

Chronic hepatitis B virus (HBV) infection is a major global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite current antiviral therapies, functional cure remains elusive due to persistent HBsAg expression and immune dysfunction. Recent therapeutic advances include direct-acting antivirals, such as entry inhibitors, siRNAs, antisense oligonucleotides, capsid assembly modulators, and HBsAg release blockers, and immunomodulatory approaches like therapeutic vaccines, Toll-like receptor (TLR) agonists, and immune checkpoint inhibitors. Combination regimens that integrate viral suppression with immune restoration offer the most promising route toward sustained HBV control. Nevertheless, challenges such as limited seroconversion, viral rebound, and safety concerns persist. This review systematically summarizes recent progress in antiviral and immunotherapeutic strategies for chronic HBV infection associated hepatitis, highlights their underlying mechanisms and clinical efficacy, and underscores the future value of rational combination therapies in achieving functional cure and reducing hepatitis B burden.