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

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

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.

Associate Editor: C.P. Day

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

1 Division of Gastroenterology, University of California-Irvine, Irvine, CA, USA

2 Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, USA

3 Department of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA

4 Department of Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA

5 Carolinas Medical Center, Charlotte, NC, USA

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

7 New England Research Institutes, Watertown, MA, USA

8 Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, USA

9 Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA

10 Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA

11 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

12 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

13 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

Corresponding author. Tel.: +1 562 826 5756; fax: +1 562 826 5436.

☆ 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

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