Review article: genetic factors that modify the outcome of viral hepatitis

Aliment Pharmacol Ther. 2014 May;39(10):1059-70. doi: 10.1111/apt.12717. Epub 2014 Mar 24.

Abstract

Background: Genetic factors can play an important role for treatment response and disease progression in chronic viral hepatitis.

Aim: To review the influence of host genetic factors on the clinical course as well as on treatment response in patients with viral hepatitis.

Methods: Review of the literature.

Results: A landmark genome-wide association study (GWAS) identified polymorphisms in the IL28B gene on chromosome 19 (19q13.13) associated with response to therapy with pegylated interferon-α (PEG-IFN) and ribavirin (RBV) and spontaneous viral clearance in acute hepatitis C. Furthermore, IL28B genotype is associated with changes of lipid metabolism and insulin resistance. A further GWAS demonstrated that ITPA genetic variants protect HCV genotype 1 patients from RBV-induced anaemia. Another polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) is associated with hepatic steatosis. Difficult-to-treat hepatitis C patients homozygous for GG had an up to five-fold lower chance of viral clearance on PEG/RBV than non-GG patients. In chronic hepatitis B patients treated with PEG-IFN several retrospective analyses of IL28B rs12980275 and rs12979860 genotypes yielded conflicting results which can be explained by the heterogeneity between the study populations. Some variants of the HLA-DP locus (HLA-DPA1 A allele and HLA-DPB1) protect against progression of chronic hepatitis B infection.

Conclusions: The determination of IL28B polymorphisms may be useful to individualise treatment options when using PEG/RBV based therapies for chronic hepatitis C infection. In contrast, so far identified genetic factors play only a minor role in chronic hepatitis B infection.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genotype
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Genetic
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a