Liver, Pancreas and Biliary TractInteraction between calcineurin inhibitors and IL-28B rs12979860 C>T polymorphism and response to treatment for post-transplant recurrent hepatitis C

BackgroundThe impact of calcineurin inhibitors on achievement of sustained virological response to antiviral therapy for post-transplant recurrent hepatitis C is controversial. This study aimed at investigating the interactions between calcineurin inhibitors and interleukin-28B (IL-28B) gene polymorphisms and sustained virological response.MethodsRetrospective study of 147 liver transplant recipients with recurrent hepatitis C, who received 48 weeks of peg-interferon-α (N = 113) or standard interferon (N = 34), in association with ribavirin. Cyclosporine and tacrolimus were administered in 68 and 79 patients, respectively. IL-28B rs12979860 allele frequency was assessed in both donors and recipients.ResultsOverall, 57 patients (38.8%) obtained sustained virological response; no difference was found between cyclosporine and tacrolimus-treated patients (42.6% vs. 35.4%, p = 0.371). Recipient and donor IL-28B genotypic frequencies were C/C = 30.6%, C/T = 51.7%, T/T = 17.7% and C/C = 44.9%, C/T = 50.3%, T/T = 4.8%, respectively. Combining donor and recipient alleles, response rates decreased from cyclosporine-treated patients carrying ≤1 T allele (56.1%) to tacrolimus-treated patients carrying ≤1 T allele (44.7%) to patients carrying ≥2 T alleles (25.0%, p = 0.0009).ConclusionsDonor and recipient rs12979860 alleles synergistically influence sustained virological response rate to antiviral treatment for recurrent hepatitis C. In patients carrying <2 T alleles cyclosporine favours a better response than tacrolimus, while no difference was found in the presence of ≥2 T alleles.