Chronic Hepatitis B (CHB) caused by infection with hepatitis B virus (HBV) currently affects 296 million people worldwide1, including 120 million persons in the Asia-Pacific region, with over 880,000 deaths per year. The highly effective preventative vaccine has no effect on existing infections and current direct acting antivirals suppress but do not eliminate viral replication. Nor do they eliminate the risk of liver cancer, with 40% of all hepatocellular carcinomas (HCC) caused by chronic HBV. A major contributor to HBV persistence in persons living with chronic HBV is the presence of a covalently closed circular DNA (cccDNA) reservoir in the nucleus of HBV infected hepatocytes that is not directly targeted by any current antiviral therapy.
There is global consensus for the need for HBV cure2, 3, to markedly reduce liver disease, improve the well-being of all persons living with CHB and eliminate HBV-related stigma. Such cures must be affordable and widely available to all who need them.
In 2019, the International Coalition to Eliminate Hepatitis B virus (ICE-HBV) released its global scientific strategy3, effectively a roadmap for HBV cure. This strategy concluded that HBV cure will likely require approaches that both specifically target the virus, and stimulate HBV specific host immune responses.
The complex HBV replication cycle offers multiple novel targets to impact viral replication, including the viral cccDNA reservoir. In turn, numerous approaches to enhance HBV specific host immune responses are in development, including therapeutic vaccines and approaches to reverse immune cell exhaustion. Many of these approaches are in pre-clinical or early phase clinical trials, with different combinations of treatments also being investigated. The current status of HBV curative research and where we are on the road towards HBV cure will be discussed.