Mutations in hepatitis C virus genotype 1b and the sensitivity of interferon-ribavirin therapy after liver transplantation

J Hepatol. 2010 May;52(5):672-80. doi: 10.1016/j.jhep.2009.10.034. Epub 2010 Mar 4.

Abstract

Background & aims: The results of post-transplant antiviral therapy for recurrent hepatitis C virus (HCV) are poor, and significant pre-transplant predictors for sustained viral response (SVR) have not yet been identified.

Methods: Pegylated interferon/ribavirin therapy was performed for more than 48 weeks in 50 patients who underwent liver transplantation (LT) for HCV genotype 1-related liver disease. Of these, 22 patients achieved SVR. The predictive potential of the viral mutations, including amino acids (aa) 70 and 91 in the Core region, interferon sensitivity-determining region (ISDR, aa 2209-2248) and interferon/ribavirin resistance-determining region (IRRDR, aa 2334-2379) in NS5A, was evaluated.

Results: In 16 patients, the sequences in the pre- and post-transplant samples were the same, except for aa 70 in the Core of 1 patient. The SVR achievement percentage was significantly lower in the Non-double wild (DW) at aa 70 and 91, the ISDR<2 and IRRDR<6 groups than in the DW (30% vs. 65%, p=0.015), the ISDR2 (35% vs. 69%, p=0.035) and IRRDR6 (25% vs. 78%, p<0.001) groups, respectively. Predictive scoring with these three items provides a newly established and significant predictor for SVR after LT (p=0.015).

Conclusion: DW, ISDR2 and IRRDR6 were found to be significant predictors for SVR after LT. In addition, it is possible that the establishment of a new scoring system consisting of these three factors may be a useful marker to predict interferon sensitivity for recurrent HCV after LT.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antiviral Agents / therapeutic use
  • Drug Tolerance
  • Female
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology*
  • Hepatitis C / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons / therapeutic use*
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / methods
  • Living Donors
  • Male
  • Middle Aged
  • Mutation
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • Tissue Donors / statistics & numerical data
  • Viral Nonstructural Proteins / genetics
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • Viral Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a