Functional cure of chronic hepatitis B virus infection: current therapeutic regimens

Abstract

Hepatitis B virus (HBV) infection remains a major cause of hepatocellular carcinoma (HCC). It is estimated that 254 million people are chronically infected with HBV, with 1.1 million deaths projected in 2025. Functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg), is important for the prevention of HCC. While nucleos(t)ide analogs maintain viral suppression in over 95% of patients, HBsAg clearance is achieved in only 2%-11%. The functional cure rate with interferon therapy is highly variable in different populations, ranging from 2% to over 40%. Consequently, functional cure remains the primary focus of novel therapeutic development. Here, we analyze the virological and immunological barriers to functional cure and summarize current therapeutic methods. Among these, novel RNA-interference-based therapeutics reduce HBsAg to below 10% of baseline in most patients. However, monotherapy with these agents results in HBsAg loss in fewer than 10% of cases. However, sequential interferon or immunomodulatory agents raise the HBsAg loss to 15%-30%. To achieve the > 50% cure rate likely required for the World Health Organization’s 2030 elimination goals, we analyze promising strategies focused on multi-target combination approaches and precision-medicine frameworks.

Keywords

Hepatitis B virus / functional cure / novel therapeutic methods / combination strategies / special populations

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