Abstract
Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.
Highlights
In the treatment naïve individuals, PegIFN/RBV achieves 40–50% sustained virologic response (SVR) rates in patients infected with in HCV genotype-1 (HCV-1) and 75% in those with HCV-2/3 infections in western countries[7]
The emergence of direct acting antiviral agents, such as telaprevir and boceprevir, has improved the SVR rates substantially and become the regimen of abbreviated therapy for patients infected with HCV-111–15
We hypothesized that the inflammatory cytokines plays a crucial role in the PegIFN/RBV treatment efficacy of chronic hepatitis C
Summary
In the treatment naïve individuals, PegIFN/RBV achieves 40–50% sustained virologic response (SVR) rates in patients infected with in HCV genotype-1 (HCV-1) and 75% in those with HCV-2/3 infections in western countries[7]. Rapid virologic response (RVR)[16], HCV genotypes[17], viral load[18,19], IL-28B polymorphisms[20,21,22,23,24,25], and host microRNAs26,27 are major predictors for treatment outcomes of PegIFN/RBV therapy. Increased Th2 cytokine production is associated with non-virological response for PegIFN/RBV therapy in chronic HCV patients[33,34]. Analysis of the inflammatory cytokines expression during HCV infection could help us realize the mechanism of viral-host interactions and identify the predictors of treatment outcome[35,36,37]. We conducted a clinical study to survey the dynamics of inflammatory cytokines during PegIFN/RBV therapy for HCV. We tried to identify immunological factors to predict the outcomes of antiviral therapy
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