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

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.

• Authors: 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, HALT-C Trial Group
• Journal: Journal of hepatology (J Hepatol) Vol. 49 Issue 4 Pg. 548-56 (Oct 2008) ISSN: 0168-8278 [Print] Netherlands
• PMID: 18619701 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• Haplotypes
• Hepacivirus (genetics)
• Hepatitis C (drug therapy, 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)