Background & Aims: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/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-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg 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, T rs12979860 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, T rs12979860 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-α/ ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
Bibliographical noteFunding Information:
This study was supported by the European Community (QLK2-2000-00836), The Swedish Society Against Cancer (Cancerfonden), The Swedish Society of Medicine, the Swedish Research Council, The Torsten and Ragnar Söderberg Foundation, the Swedish Foundation for Strategic Research, the VIRGO consortium (BSIK 03012), the Leenaards foundation, the Swiss National Science Foundation (SNF 32003B-127613), Hoffmann La Roche, and The Epicept Corporation.
- Hepatitis C
- IL28 B
- Viral kinetics