Toward Curative Immunomodulation Strategies for Chronic Hepatitis B Virus Infection

Chronic hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality worldwide. HBV surface antigen loss is considered a functional cure and is an ideal goal for antiviral therapy. However, current treatment regimens, including nucleos(t)ide analogues or interferons monotherapy and combination therapy, rarely achieve this goal in chronic hepatitis B patients. Nucleos(t)ide analogues (NAs), as well as many direct antiviral drugs in ongoing development, are able to inhibit HBV replication and gene expression, but it is hard to achieve immune control and prevent recurrence after therapy cessation. Host immunity, especially HBV-specific T cell response, is proven to play a critical role in control or clearance of HBV infection. Considering HBV chronically infected patients display varying degrees of dysfunction regarding their immune system, novel approaches to enhancing antiviral immune responses are necessary in order to combine with current antiviral agents. In this Review, we focus on the role of innate and adaptive immune responses in HBV immunopathogenesis and discuss attractive strategies or drugs that aim to activate or rebuild antiviral immunity to achieve the goal of an HBV functional cure.