Hepatitis B functional cure: Current and future perspective

Core Tip

Core Tip: Achieving a functional cure for chronic hepatitis B, defined as sustained hepatitis B surface antigen loss with undetectable hepatitis B virus (HBV) DNA, remains challenging due to the persistence of covalently closed circular DNA (cccDNA) and immune dysfunction. While standard therapies, such as nucleos(t)ide analogues and pegylated interferon, yield low seroclearance rates, novel therapeutics targeting various steps in the life cycle of HBV-such as cccDNA silencing, RNA degradation, capsid modulation, and immune restoration- show promise. Combinatorial approaches, including small interfering RNA, checkpoint inhibitors, and therapeutic vaccines, are being evaluated. Identifying predictive biomarkers and optimizing the timing for treatment cessation may improve treatment outcomes.