None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis

PLoS One. 2012;7(11):e48217. doi: 10.1371/journal.pone.0048217. Epub 2012 Nov 16.

Abstract

Background & aims: A combination of pegylated interferon-alpha and ribavirin (PR) is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR) to PR has been well documented in patients with CHC genotype-1 (GT1), but it is controversial in genotype-2 (GT2) CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP) of IL28B on the treatment responses of PR in patients with CHC GT2.

Method: 197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV) genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM) analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias.

Results: The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR), cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2.

Conclusions: The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Data Interpretation, Statistical*
  • Female
  • Genotype*
  • Hepacivirus / drug effects
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Ribavirin
  • Interferons

Grants and funding

This work was supported by NMRP: 98-3112-B-182A-003 and NMRP: 360021 from the National Science Council, Taiwan, and CMRPG 390682, 37542, 360463 from Chang Gung Memorial Hospital. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.