An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response

Gastroenterology. 2010 Sep;139(3):821-7, 827.e1. doi: 10.1053/j.gastro.2010.05.079. Epub 2010 Jun 2.

Abstract

Background & aims: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.

Methods: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.

Results: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7).

Conclusions: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Chi-Square Distribution
  • Drug Therapy, Combination
  • Female
  • Gene Frequency
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Italy
  • Logistic Models
  • Male
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Genetic*
  • Prospective Studies
  • RNA, Viral / blood
  • Recombinant Proteins
  • Recurrence
  • Ribavirin / therapeutic use*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b