Clin Mol Hepatol.  2022 Jan;28(1):17-30. 10.3350/cmh.2021.0093.

Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus

Affiliations
  • 1Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
  • 3Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
  • 4Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea

Abstract

Hepatitis B virus (HBV) affects approximately 250 million patients worldwide, resulting in the progression to cirrhosis and hepatocellular carcinoma, which are serious public health problems. Although universal vaccination programs exist, they are only prophylactic and not curative. In the HBV life cycle, HBV forms covalently closed circular DNA (cccDNA), which is the viral minichromosome, in the nuclei of human hepatocytes and makes it difficult to achieve a complete cure with the current nucleos(t)ide analogs and interferon therapies. Current antiviral therapies rarely eliminate cccDNA; therefore, lifelong antiviral treatment is necessary. Recent trials for antiviral treatment of chronic hepatitis B have been focused on establishing a functional cure, defined by either the loss of hepatitis B surface antigen, undetectable serum HBV DNA levels, and/or seroconversion to hepatitis B surface antibody. Novel therapeutic targets and molecules are in the pipeline for early clinical trials aiming to cure HBV infection. The ideal strategy for achieving a long-lasting functional or complete cure might be using combination therapies targeting different steps of the HBV life cycle and immunomodulators. This review summarizes the current knowledge about novel treatments and combination treatments for a complete HBV cure.

Keyword

Hepatitis B virus; Antiviral therapy; Complete cure
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