ReviewChronic hepatitis B: A wave of new therapies on the horizon

•This articles introduces a symposium marking the 50th anniversary of the discovery of the Australia antigen.•Current antiviral therapies for chronic hepatitis B suppress viral replication, but rarely eradicate the virus.•The persistence of viral cccDNA in the nucleus of hepatocytes is the principal obstacle to curative therapy.•Many new treatment approaches are now under development, and some may be more effective in eliminating cccDNA.•As for hepatitis C, optimal therapy for hepatitis B may consist of a combination of drugs with different targets.

This year marks the 50th anniversary of the discovery of the Australia antigen (Blumberg et al., 1965), which in 1967 was identified to be the hepatitis B virus (HBV) surface antigen. Even though several antiviral medications have been in use for the management of chronic HBV infection for more than 20 years, sustained clearance of HBsAg, similar to the sustained viral response (SVR) or cure in chronic hepatitis C, occurs in only a minority of treated patients. Moreover, even after 10 years of effective suppression of HBV viremia with current therapy, there is only a 40-70% reduction in deaths from liver cancer. Recent success in developing antivirals for hepatitis C that are effective across all genotypes has renewed interest in a similar cure for chronic HBV infection. In this article, we review a wave of newly identified drug targets, investigational compounds and experimental strategies that are now under clinical evaluation or in preclinical development. The paper forms part of a symposium in Antiviral Research on “An unfinished story: From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.”