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

Abstract

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.

Keywords::

• calcineurin inhibitor
• cyclosporine
• hepatitis C
• immunosuppression
• liver transplant
• tacrolimus

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript