Hepatitis B Virus: Pathogenesis and Therapeutic Approaches

Hepatitis B virus (HBV) was discovered in the 1960s but has yet to be cured despite global efforts. Multiple approaches to the development and clinical application of direct-acting antiviral compounds are efficacious in reducing virus titers in the blood, but no treatments have been devised that will result in a sterilizing cure. Part of the problem in eliminating HBV is the lack of universal vaccination, inadequate resources for diagnosis needed to prevent virus spread, and intravenous drug abuse. Much research has focused on the attempted elimination of covalently closed circular (ccc) HBV DNA, which is the template for virus replication, but this has proven challenging. Relatively little effort has been put into targeting HBV X (HBx), which supports viral gene expression and replication. In addition, HBx is a major contributor to the pathogenesis of chronic liver disease and the development of hepatocellular carcinoma. Future research will involve the development of combination therapies, some of which may also include the epigenetic targeting of HBx, to help promote a functional cure for this disease, which claims the lives of hundreds of millions of people worldwide each year. Hepatitis B Virus - Pathogenesis and Therapeutic Approaches outlines some of these barriers to virus elimination, especially among developing countries, and suggests therapeutic approaches that will contribute to a functional cure to decrease hepatitis B-associated morbidity and mortality.