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

Timothy R. Morgan, Richard W. Lambrecht, Herbert L. Bonkovsky, Raymond T. Chung, Deepa Naishadham, Richard K. Sterling, Robert J. Fontana, William M. Lee, Marc G. Ghany, Elizabeth C. Wright, Thomas R. O'Brien

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)548-556
Number of pages9
JournalJournal of Hepatology
Volume49
Issue number4
DOIs
StatePublished - Oct 1 2008

Keywords

  • Chronic/genetics
  • Gene frequency
  • Genetic
  • Hepatitis C
  • Interferon-alfa/therapeutic use
  • Polymorphism

ASJC Scopus subject areas

  • Hepatology

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    Morgan, T. R., Lambrecht, R. W., Bonkovsky, H. L., Chung, R. T., Naishadham, D., Sterling, R. K., Fontana, R. J., Lee, W. M., Ghany, M. G., Wright, E. C., & O'Brien, T. R. (2008). DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial. Journal of Hepatology, 49(4), 548-556. https://doi.org/10.1016/j.jhep.2008.05.011