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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.

SUBMITTER: Morgan TR

PROVIDER: S-EPMC3903339 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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

Morgan Timothy R TR Lambrecht Richard W RW Bonkovsky Herbert L HL Chung Raymond T RT Naishadham Deepa D Sterling Richard K RK Fontana Robert J RJ Lee William M WM Ghany Marc G MG Wright Elizabeth C EC O'Brien Thomas R TR

Journal of hepatology 20080605 4

<h4>Background/aims</h4>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.<h4>Methods</h4>SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleot ...[more]

PMID: 18619701

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Project description:BACKGROUND:IL28B gene polymorphism is the best baseline predictor of response to interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new IFN-L4 polymorphism was identified as first potential functional variant for induction of IL28B expression. Individualization of interferon alfa-based therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to optimize virologic outcome and economic resources. METHODS:Optimization of treatment outcome prediction was assessed by combination of different IL28B and IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n?=?385), 2/3 (n?=?267), and 4 (n?=?220) infection treated with pegylated interferon alfa (PEG-IFN) and ribavirin with (n?=?79) or without telaprevir. Healthy people from Germany (n?=?283) and Egypt (n?=?96) served as controls. RESULTS:Frequencies of beneficial IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients in comparison to controls (20-35% vs. 46-47%) this was also true for ss469415590 TT/TT (20-35% vs. 45-47%). Single interferon-lambda SNPs (rs12979860, rs8099917, ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3, and 4 infected patients while no association was observed for genotype 2. Interestingly, in genotype 3 infected patients, best SVR prediction was based on IFN-L4 genotype. Prediction of SVR with high accuracy (71-96%) was possible in genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin combination therapy by selection of beneficial IL28B rs12979860 C/C and/or ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%) rates was based on the presence of at least one beneficial genotype of the 3 IFN-lambda SNPs. CONCLUSION:IFN-L4 seems to be the best single predictor of SVR in genotype 3 infected patients. For optimized prediction of SVR by treatment with dual combination or first generation PI triple therapies, grouping of interferon-lambda haplotypes may be helpful with positive predictive values of 71-96%.

Dataset Information

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

Publications

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

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