Identification of naïve HVC-4 patients who may be treated with pegylated-interferon and ribavirin according to IL28B polymorphisms

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Abstract

Background

The current treatment of HCV-4 patients is dual therapy with PEG-IFN and ribavirin; however, new drugs against this genotype will be available within few months. Despite the evidenced good virological response in IFN-free regimens, the high cost of these new therapies will require patient selection. In our paper we propose the use of both rs8099917 and rs12979860 IL28-B polymorphisms, in order to identify potentially categories of SVR, null-responder and relapse and consequently to choose the dual therapy or novel approach.

Methods

One hundred and sixty-nine patients with chronic hepatitis C and genotype 4 treated with pegylated interferon and ribavirin for 48 weeks were retrospectively studied. All patients were genotyped for rs8099917 and rs12979860 interleukin-28B polymorphisms.

Results

80 patients with SVR (88.8%) had the TT/CC or TT/TC (rs8099917/rs12979860) (p < 0.001) genotypes; the null-responders (n = 13), 9 (69.2%) showed the GG/TT allelic distribution (p < 0.001); relapsers showed a prevalent distribution of the TG/TC genotype (83.3%) (p < 0.001). The 6 (100%) breakthrough patients showed TT/TC genotype, while the partial responders patients did not show any particular IL-28B genetic profile. Genetic profiles different from TT/CC showed 94.9% negative predictive value for SVR, with 92.6% of sensitivity and 65.2% of specificity. Insulin-resistance, diabetes and liver fibrosis were not relevant in our multivariate analysis.

Conclusions

The combination of both rs8099917/rs12979860 polymorphisms is useful for early identification of SVR, null-responders and relapsers. This could be used to chose between standard dual therapy or novel approach with IFN-free regimens.

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