Influence of Genes Suppressing Interferon Effects in Peripheral Blood Mononuclear Cells during Triple Antiviral Therapy for Chronic Hepatitis C

<div><p>The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (<i>IL28B</i>) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable <i>IL28B</i> genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for <i>A20, SOCS1</i>, and <i>SOCS3</i>, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as <i>IRF1</i> were significantly higher at 8 h in patients with an unfavorable <i>IL28B</i> genotype than in those with a favorable one (<i>P</i> = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of <i>IRF1</i> at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable <i>IL28B</i> genotype (<i>P</i> = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to <i>IL28B</i> genotypes, paralleling treatment efficacy.</p>