Current and future directions of management of hepatitis B: steps toward a cure

Universal hepatitis B virus vaccination has been effective in reducing incident chronic hepatitis B but will not have the requisite effect on the prevalence of end-stage liver disease in chronically infected persons. The natural history and immunological stages of hepatitis B virus infection are still being defined. Over three decades, current therapies have reduced morbidity from chronic hepatitis B. The majority require nucleoside analog maintenance therapy. The preferential preservation of covalently closed circular DNA (cccDNA), and capsid reverse transcriptase-cccDNA interactions currently precludes cure in most. A functional cure in the host may require several synergistic antiviral and immunological intercessions. The correct sequencing and combinations of treatment with either host or viral targeting agents have yet to be determined. Proven surrogates for cccDNA for clinical trials are required. Different strategies may become apparent for patients at different stages of the disease. Curative therapies will require affordability. This review focuses on steps toward a cure.