Sirolimus and everolimus: inhibitors of mammalian target of rapamycin in liver transplantation

Sirolimus (SRL) and everolimus are members of a relatively new class of immunosuppressants that impair cell cycle proliferation by inhibition of the mammalian target of rapamycin. These agents have been evaluated and licensed for use in kidney transplantation where they are used predominantly as maintenance immunosuppression because they lack the nephrotoxicity associated with calcineurin inhibitors. Neither SRL nor its newer analogue everolimus are currently licensed for use in liver transplantation, but both have been used with varying degrees of success and efficacy in this setting. Concern has been expressed about a potential association between de novo use of SRL and both a high incidence of hepatic artery thrombosis after liver transplantation and impaired wound healing, and thus, subsequent development has focused on the use of SRL in response to calcineurin inhibitor toxicity in patients with established liver transplants as well as using its potential antitumor effects in patients transplanted for malignancy. This article reviews the reported experience of mammalian target of rapamycin inhibitor therapy in liver transplantation.