From Bench to Bedside: Progress in Hepatitis B Treatment Modalities

Abstract

Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820,000 deaths worldwide in 2019. The diagnosis of HBV infection requires serologic testing for HBsAg and, for acute infection, additional testing for hepatitis B core IgM antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions includes HBV DNA testing, while assessment of liver disease activity and stage is based mainly on aminotransferases, platelet counts, and elastography. Universal immunization of infants, including birth dose vaccination, is the most effective means of preventing chronic HBV infection. Two vaccines with improved immunogenicity for adults have recently been approved in the US and EU, and their availability is expected to expand. Pegylated interferon and nucleos(t)ide analogues, which are now used in therapy, can stop the development of cirrhosis and hepatocellular cancer, but they cannot completely eradicate the virus and seldom remove HBsAg. Patients with severe or active liver disease, cirrhosis, or elevated HBV DNA levels should consider treatment. Clinical trials are underway to explore novel antiviral and immunomodulatory treatments with the goal of achieving functional cure, or the removal of HBsAg. The World Health Organization (WHO) has set a 2030 deadline for the eradication of HBV infection. Achieving this objective would require developing curative medicines, increasing screening, diagnosis, and connection to care, as well as removing stigma.