4.8 Article

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C

期刊

JOURNAL OF HEPATOLOGY
卷 55, 期 5, 页码 980-988

出版社

ELSEVIER
DOI: 10.1016/j.jhep.2011.01.050

关键词

Hepatitis C; IL28 B; Viral kinetics

资金

  1. European Community [QLK2-2000-00836]
  2. The Swedish Society Against Cancer (Cancerfonden)
  3. The Swedish Society of Medicine
  4. Swedish Research Council
  5. The Torsten and Ragnar Soderberg Foundation
  6. Swedish Foundation for Strategic Research
  7. VIRGO consortium [BSIK 03012]
  8. Leenaards foundation
  9. Swiss National Science Foundation [SNF 32003B-127613]
  10. Hoffmann La Roche
  11. The Epicept Corporation

向作者/读者索取更多资源

Background & Aims: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-alpha/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs. Methods: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naive Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-alpha 2a (180 mu g weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates. Results: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T-rs12979860) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted p <0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p <0.001). In univariate analyses, Trs12979860 was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, Trs12979860 was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline. Conclusions: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-alpha/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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