Impact of IL28B gene polymorphisms on interferon-λ3 plasma levels during pegylated interferon-α/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV

The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-/ribavirin therapy. A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56 of patients. IL28B rs12979860 alleles were genotyped using the 5 nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-3 plasma levels or in their median values. In contrast, median IFN-3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.756.3) versus 15.6 (15.630.3) pg/mL, respectively; P0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-3 at week 4 of therapy did not predict SVR. The exogenous administration of IFN- may induce IFN-3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.