Unmet Needs in Clinical and Basic Hepatitis B Virus Research

Abstract

Chronic hepatitis B (CHB) has become a treatable and controllable disease. The current nucleos(t)ide analogue (NUC) and pegylated interferon therapies effectively help slow disease progression and reduce the risk of cirrhosis, hepatocellular carcinoma (HCC), and CHB-associated mortality. Long-term viral suppression is easily achievable by NUC therapy, with limited adverse reactions. However, several unmet requirements still exist, including safety and risk-stratified HCC surveillance among patients who received long-term NUC therapy. Criteria for determining which patients should receive finite-duration NUC therapy and which should receive combination therapy with both NUC and pegylated interferon remain unsettled. The management of hepatitis B virus (HBV) e antigen-positive viremic patients with normal liver function and the incorporation of new biomarkers to help manage CHB require further exploration. To achieve functional cure (ie, HBV surface antigen seroclearance) and complete cure (ie, eradication of covalently closed circular DNA) of CHB, several challenges in basic research must be addressed, including the development of an efficient cell culture system and animal models for HBV investigation, development of treatment to eradicate covalently closed circular HBV DNA, and development of immunotherapy for CHB. This brief review focuses on unmet needs in both clinical and basic HBV research.