The adverse pharmacology of calcineurin inhibitors and their impact on hepatitis C recurrence after liver transplantation: Implications for clinical practice

Calcineurin inhibitors are widely used as maintenance immunosuppressants in solid-organ transplantation to minimize the risk of allograft rejection. Although the use of these agents has transformed the outcomes for patient and graft survival, this has come at a cost, notably the well-known adverse events of nephrotoxicity and metabolic abnormalities, to name a few. Over the last decade, tremendous interest has also focused on the impact of these medications on the replication of hepatitis C virus (HCV), with cyclosporine in particular having a negative effect on viral replication in vitro. Although small retrospective studies suggested that there may be a beneficial effect with cyclosporine on the progression of recurrent HCV and response to interferon, these findings have not been validated in several well-designed randomized controlled trial studies. The authors will review the pharmacology and pharmacokinetics of these well-known drugs and discuss the impact of these medications on the natural history of HCV recurrence after liver transplantation.