Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin
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文摘

Background & Aims

Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients.

Methods

<p>rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400 mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 μg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up.

Results

<p>rs12979860 genotyping revealed that 27 (37.5 % ) patients had C/C, 39 (54.2 % ) T/C, and 5 (6.9 % ) T/T. Thirteen patients (18.1 % ) became HCV RNA negative at week 2 and an additional 30 (41.7 % ) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8 % ; T/C or T/T: 50.0 % ). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36–6.02] median; [range] vs. 3.50; [0.14–5.62]; log IU HCV-RNA/ml; p <0.001; week 4: 4.97; [1.21–6.20] vs. 4.49; [1.16–6.23]; p = 0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar.

Conclusions

<p>IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined.

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