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

J Hepatol. 2010 Dec 8. [Epub ahead of print]

Scherzer TM, Hofer H, Staettermayer AF, Rutter K, Beinhardt S, Steindl-Munda P, Kerschner H, Kessler HH, Ferenci P.

Medical University of Vienna, Internal Medicine III, Department of Gastroenterology and Hepatology, Austria.

Abstract

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

METHODS: : rs12979860 and rs8099917 were analyzed by the StepOnePlus Real time PCR system in 71 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 treatment and follow-up.

RESULTS: : rs12979860 genotyping revealed that 27 (37.5%) pts had C/C, 39 (54.2%) T/C and 5 (6.9%) T/T. Thirteen pts (18.1%) became HCV RNA negative at week 2 and additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; C/T or T/T: 50.0%). Irrespective of the ribavirin dose the viral load decline was larger than in those with T allele (C/T 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 showed similar results.

CONCLUSION: : 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 of C/C patients needs to be determined.

Copyright © 2010. Published by Elsevier B.V.

PMID: 21145807 [PubMed - as supplied by publisher]

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