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

J Hepatol. 2008 Oct;49(4):548-56. doi: 10.1016/j.jhep.2008.05.011. Epub 2008 Jun 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Haplotypes
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interleukin-10 / genetics
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Recombinant Proteins
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • White People / genetics

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Interleukin-10
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

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