Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study

BMC Infect Dis. 2015 Mar 26:15:156. doi: 10.1186/s12879-015-0888-x.

Abstract

Background: The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment.

Methods: Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy.

Results: The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p=0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p=1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p=0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy.

Conclusions: In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Case-Control Studies
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use
  • Severity of Illness Index
  • Treatment Failure
  • Viral Load

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a