Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

Background: Predictors of sustained virological response (SVR) to antiviral therapy post-liver transplantation (LT) for chronic hepatitis C are needed. In non-transplanted patients, viral kinetics can predict SVR. Objectives: To determine the early viral kinetics in LT recipients with different immunosuppression (tacrolimus - Tac- vs. cyclosporine - CsA-) during treatment with peg-IFN + RBV. Study design: Prospective pilot study in HCV-1b infected patients: (LT CsA n = 8; Tac n = 8; non-LT n = 4), treated with IFN alpha-2a vs. alpha-2b (180 mu g or 1.5 mu g/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70 ng/mL, respectively. HCV-RNA was quantified before treatment and after 3, 6, 12 h; days 1-6; and weeks 4, 12, 24, 48 and 78 (follow-up). Results: Different kinetics were observed: early viral load declines with shoulder phase (n = 12), delayed monophasic without first phase (n = 5, all CsA), and biphasic (n = 1) or flat (n = 1), without influence of IL28B rs12979860 donor/recipient alleles. In LT, median declines (log(10) UI/mL) at week 4 were -3.62 and -1.49 for Tac vs. CsA; and -2.10 vs.-1.50 for IFN alpha-2a vs. alpha-2b (NS), with a trend for faster declines in Tac patients. Generalized additive models suggested a cut-off for predicting response in LT patients of 30 days for Tac, but beyond day 40 for CsA. Conclusion: In LT, the viral kinetics during peg-IFN + RBV treatment is delayed. HCV-RNA at 48 h. may not be predictive of response, and CsA-immunosupressed patients with delayed monophasic declines may potentially achieve ETVR and SVR despite unfavourable or absent early viral load declines. (C) 2011 Elsevier B.V. All rights reserved.