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Hepatitis B virus variants

Nature Reviews Gastroenterology & Hepatology volume 6, pages 453–462 (2009)Cite this article

Abstract

HBV replicates through reverse transcription of an RNA intermediate; the inherent lack of proofreading causes a high mutation frequency. Mutations in the precore and core promoter regions that abolish or reduce the production of hepatitis B e antigen occur most commonly. Patients with these HBV variants remain viremic and can develop progressive liver disease. Mutations in the core promoter region are associated with an increased risk of hepatocellular carcinoma. Exogenous selection pressure might favor certain mutations. Mutations in the HBV polymerase that confer resistance to nucleoside and nucleotide analog treatments are a major barrier to the success of therapy for hepatitis B. The development of antiviral drug resistance negates the initial treatment response and can lead to hepatitis flares and hepatic decompensation. Prompt addition of another drug to which the virus is not cross-resistant is required. Mutations in the HBV surface protein that facilitate escape from host immunity are responsible for the failure of immune prophylaxis in infants who received HBV vaccine and in liver transplant recipients who received hepatitis B immune globulin.

Key Points

  • Mutations in the precore and core promoter regions are the most common naturally occurring mutations in HBV

  • Mutations in the core promoter, which are most commonly associated with HBV genotype C, are associated with an increased risk of hepatocellular carcinoma

  • Selection for mutations in the reverse transcriptase region of the HBV polymerase is a major barrier to the success of nucleoside or nucleotide analog treatment of hepatitis B

  • Antiviral drug resistance initially manifests as virologic breakthrough and might be followed by biochemical breakthrough, hepatitis flare and hepatic decompensation

  • Antiviral treatment should be initiated with nucleoside or nucleotide analogs that have high genetic barriers to resistance

  • Immune-escape HBV surface mutations are responsible for the failure of immune prophylaxis in infants who received HBV vaccine and in liver transplant recipients who received hepatitis B immune globulin

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Figure 1: Transcription and translation of HBV precore and core promotor variants.
Figure 2: Antiviral drug resistance mutations.

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  1. Division of Gastroenterology, University of Michigan Health System, Ann Arbor, MI, USA

    Watcharasak Chotiyaputta & Anna S. F. Lok

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Anna S. F. Lok has carried out consultancy work for Roche, Gilead, Schering-Plough, Bristol-Myers Squibb and Pharmasset, and has received grant or research support from Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, Novartis, Gilead, Innogenetics and Nabi. W. Chotiyaputta declares no competing interests.

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Chotiyaputta, W., Lok, A. Hepatitis B virus variants. Nat Rev Gastroenterol Hepatol 6, 453–462 (2009). https://doi.org/10.1038/nrgastro.2009.107

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