Immunosuppression in liver transplant

Abstract

The increasing potency of immunosuppression (IS) agents resulted in significantly decreased rates of steroid resistant rejection and rejection related graft loss in liver transplantation (LT). Currently, more than two thirds of late mortality after LT is unrelated to graft function. However, the increased benefit of more potent IS drugs, coupled with the prolonged survival of transplant recipients led to longer patients exposure to these drugs and their unwanted adverse effects, creating a double-edged sword. In this article the authors describe the mechanism of action and the adverse effects of the most commonly used immunosuppressed drugs, and the most commonly used IS regimens for both induction and maintenance regimens. The balance between the ideal IS regimen to prevent rejection and the need to minimize the dose of IS drugs in order to prevent the adverse effects related to its use requires the knowledge of the science and the experience with the art of medicine. The different protocols aimed at protecting renal function and preventing the development of de novo cancer and metabolic syndrome are discussed here. The main causes of mortality late after liver transplant are associated with prolonged use of IS medications, and clear evidence exists about over-immunosuppression of recipients of liver transplant. The current status of strategies of IS minimization and withdrawal are reviewed in this article, with evaluation of its benefits and pitfalls.

Keywords: Azathioprine; Calcineurin inhibitors; Cyclosporine; Everolimus; Immunosuppression; Immunosuppression induction; Immunosuppression maintenance; Immunosuppression minimization; Immunosuppression withdrawal; Liver transplantation; Mammalian target of rapamycin inhibitors; Monoclonal antibodies; Mycophenolate mofetil; Sirolimus; Tacrolimus; Tolerance.