Vitamin D pathway gene variants and HCV-2/3 therapy outcomes

BACKGROUND: The combination of ribavirin and pegylated-interferon-α is considered the standard of care for HCV-2/3 genotypes treatment. The immune system plays a key role in the achievement of the sustained virological response (SVR). Vitamin D seems to influence antiviral response in chronic hepatitis C and its pathway is controlled by polymorphic genes as CYP27B1, CYP24A1 and VDR. In this study, we have investigated the correlation among the treatment outcomes and single nucleotide polymorphisms (SNPs) in the above mentioned genes and IL28B ones. METHODS: One hundred and twelve HCV-2/3 patients treated with interferon plus ribavirin were retrospectively studied; allelic discrimination was performed by real-time PCR. RESULTS: CYP24A1rs2585428, IL28Brs12979860 and rs8099917 SNPs affected the non response and BMI, Metavir score, IL28Brs8099917TT and CYP24A1rs2585428GG were the only factors able to predict it. SVR was predicted by Metavir score, HCV-RNA at baseline and early virological response (EVR). IL28Brs12979860 SNP and HCV-RNA were also related to rapid virological response (RVR). EVR was predicted by BMI, Metavir score and CYP24A1rs2585428 SNP. IL28Brs8099917TT and FokITT were relapse prediction factors. CONCLUSIONS: As well as to non genetic factors, SNPs in vitamin D pathway seem to have a role in HCV-2/3 therapy outcomes. This study reveals the likely usefulness of pharmacogenetic-based ribavirin and interferon therapy to help identify patients for whom therapy could be successful or not, also considering the new future expensive therapy options. To date, no similar data were published on these viral genotypes, but further studies in different and bigger cohorts are needed.