Gastroenterology

Gastroenterology

Volume 139, Issue 3, September 2010, Pages 821-827.e1
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
An IL28B Polymorphism Determines Treatment Response of Hepatitis C Virus Genotype 2 or 3 Patients Who Do Not Achieve a Rapid Virologic Response

https://doi.org/10.1053/j.gastro.2010.05.079Get rights and content

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.

Section snippets

Patient and Control Populations

The primary study was a multicenter randomized controlled trial that recruited patients from 13 clinical sites in Italy.5 In the original study, 70 patients were randomized to standard treatment duration (24 wk; standard duration [SD], 24) and 213 to variable duration (VD) according to week 4 response: patients achieving RVR were treated for 12 weeks (VD12); while those not achieving RVR were treated for 24 weeks (VD24). Patients received pegIFN-alfa-2b (PEG-Intron; Schering-Plough, Kenilworth,

Patients

A total of 268 patients were included in this analysis. All patients were Caucasian, 213 patients were infected with genotype 2 HCV, and 55 patients were infected with genotype 3 HCV. Baseline demographic, biochemical, and virologic characteristics of the patients are reported in Table 1. Sixty-eight patients were randomized to 24 weeks of standard therapy, and 200 patients were randomized to variable duration therapy (Supplementary Figure 1). There were no significant differences in baseline

Discussion

We report on the role and relevance of the recently described IL-28B genetic polymorphism to PegIFN and RBV treatment outcome in the setting of chronic infection with genotype 2 or 3 HCV. This unique cohort, from a prospectively performed landmark clinical trial,5 has allowed us to carefully evaluate the interaction between this genetic determinant and treatment response in patients who received a variable duration of therapy based on week 4 virologic response.

The data indicate that the IL-28B

References (19)

  • M. von Wagner et al.

    Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C

    Gastroenterology

    (2005)
  • P.J. Scheuer

    Classification of chronic viral hepatitis: a need for reassessment

    J Hepatol

    (1991)
  • D. Ge et al.

    Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance

    Nature

    (2009)
  • Y. Tanaka et al.

    Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C

    Nat Genet

    (2009)
  • V. Suppiah et al.

    IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy

    Nat Genet

    (2009)
  • M.G. Ghany et al.

    Diagnosis, management, and treatment of hepatitis C: an update

    Hepatology

    (2009)
  • A. Mangia et al.

    Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3

    N Engl J Med

    (2005)
  • O. Dalgard et al.

    Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

    Hepatology

    (2008)
  • M.L. Shiffman et al.

    Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3

    N Engl J Med

    (2007)
There are more references available in the full text version of this article.

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Conflicts of interest These authors disclose the following: Alexander Thompson, Kevin Shianna, David Goldstein, and John McHutchison are co-inventors of a patent application based on the interleukin-28B discovery. The remaining authors disclose no conflicts.

Funding Supported by funding from the Duke Clinical Research Institute, a generous research gift from the Richard B. Boebel Family Fund, the National Health and Medical Research Council of Australia, the Gastroenterology Society of Australia, and the Royal Australasian College of Physicians (A.J.T.).

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