Journal of Hepatology
Volume 49, Issue 4 , Pages 548-556, October 2008

DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial☆☆☆

  • Timothy R. Morgan

      Affiliations

    • Division of Gastroenterology, University of California-Irvine, Irvine, CA, USA
    • Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 562 826 5756; fax: +1 562 826 5436.
    • ,
  • Richard W. Lambrecht

      Affiliations

    • Department of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    • ,
  • Herbert L. Bonkovsky

      Affiliations

    • Department of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    • Department of Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    • Carolinas Medical Center, Charlotte, NC, USA
    • ,
  • Raymond T. Chung

      Affiliations

    • Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA, USA
    • ,
  • Deepa Naishadham

      Affiliations

    • New England Research Institutes, Watertown, MA, USA
    • ,
  • Richard K. Sterling

      Affiliations

    • Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, USA
    • ,
  • Robert J. Fontana

      Affiliations

    • Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
    • ,
  • William M. Lee

      Affiliations

    • Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
    • ,
  • Marc G. Ghany

      Affiliations

    • Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
    • ,
  • Elizabeth C. Wright

      Affiliations

    • Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
    • ,
  • Thomas R. O’Brien

      Affiliations

    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
    • ,
  • the HALT-C Trial Group

Received 20 December 2007; received in revised form 4 May 2008; accepted 8 May 2008. published online 05 June 2008.

Associate Editor: C.P. Day

Background/Aims

Certain host genetic polymorphisms reportedly affect the likelihood of a sustained virological response (SVR) to interferon treatment in subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we evaluated genetic associations among patients infected with HCV genotype 1 who had failed previous interferon treatment.

Methods

SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleotide polymorphisms (SNPs) were selected on the basis of previously reported associations with treatment response. Genotypes were assessed by polymerase chain reaction-based assays. The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype.

Results

Among 637 non-Hispanic Caucasian patients there were no significant associations between genotype for any individual SNP (IL10−1082, IL10−592, TNF−308, TNF−238, TGFB1 codon 25, CCL2−2518, EPHX1 codon 113 and AGT−6) and SVR, but SVR was more common among the patients who were homozygous for the ACC IL10 promoter diplotype (adjusted odds ratio, 3.24; 95% confidence interval, 1.33–7.78; p=0.001).

Conclusions

Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR.

Keywords: Hepatitis C, Chronic/genetics, Polymorphism, Genetic, Interferon-alfa/therapeutic use, Gene frequency

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☆ Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: T.R. Morgan is a consultant, is on the speaker’s bureau and receives research support; R.T. Chung receives research support; R.K. Sterling is a consultant, on the speaker’s bureau, and receives research support; R.J. Fontana is on the speaker’s bureau; and W.M. Lee receives research support. Authors with no financial relationships related to this project are: R.W. Lambrecht, H.L. Bonkovsky, D. Naishadham, M.G. Ghany, E.C. Wright, and T.R. O’Brien. This is a NIH funded study.

☆☆ This is publication number 30 from the HALT-C Trial Group.

PII: S0168-8278(08)00354-1

doi:10.1016/j.jhep.2008.05.011

Journal of Hepatology
Volume 49, Issue 4 , Pages 548-556, October 2008

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