Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus

J Gastroenterol Hepatol. 2015 Jun;30(6):1040-8. doi: 10.1111/jgh.12890.

Abstract

Background/aims: Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C (CHC) patients.

Methods: This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 1 and 6 HCV received antiviral therapy were included. Host IL-28B rs12979860/rs8099917 and PNPLA3 rs738409 genotype were tested. The primary outcome was sustained virologic response (sustained virologic response [SVR]: undetectable HCV RNA 24 weeks post-treatment).

Results: From 305 patients had positive antibody to HCV, 52 and 31 patients infected by genotype 1 and 6 HCV, respectively were recruited. Mean age was 58 ± 11 years; 70% were male. Mean baseline HCV RNA was 6.8 ± 2.7 log IU/ml. The SVR for patients infected by genotype 1 and 6 HCV was 67.3% and 90.3%, respectively. The proportions of IL28B genotypes were 78%, 21%, and 1% for TT/TG/GG at rs8099917, and 81%, 18%, and 1% for CC/TC/TT at rs12979860, respectively. The proportions of PNPLA3 rs738409 genotypes were 16%, 36%, and 48% for GG/GC/CC. IL28B genotype was significantly associated with SVR in patients infected by genotype 1 but not genotype 6 HCV, with 80% versus 38% of patients infected by genotype 1 achieved SVR carried TT versus TG/GG at rs8099917, respectively (P=0.003). PNPLA3 genotype was not associated with SVR.

Conclusions: IL28B gene with rs8099917 T allele as an independent predictor of SVR in Chinese CHC patients infected by genotype 1 but not genotype 6 HCV.

Keywords: cirrhosis; early virologic response; liver biopsy; rapid virologic response; sustained virologic response; transient elastography.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antiviral Agents / therapeutic use*
  • Asian People
  • Cohort Studies
  • Female
  • Genetic Association Studies*
  • Genotype*
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Hepatitis C / virology*
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Lipase / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • Membrane Proteins
  • Interferons
  • Lipase
  • adiponutrin, human