Evolution Of Immunosuppression In Liver Transplantation

We are currently entering a new era of immunosuppressive therapy in liver transplantation (LT). Since the 1980s, calcineurin inhibitors (CNI) have been the mainstay of both early and late immunosuppressive regimes following LT. The occurrence of significant adverse events with current regimes of CNI combined with tapered corticosteroids, in particular nephrotoxicity, neurotoxicity and hypertension, has been responsible for a changing view of immunosuppression with increased availability of newer potentially less toxic agents. Combination regimes of various classes of immunosuppressive drugs, the addition of other drug types with reduction or withdrawal of CNI for treatment-related toxicity, or monotherapy with non-CNI agents are increasingly being utilised. Early corticosteroid withdrawal and steroid-free regimens have been successfully used in both children and adults. The use of induction therapy with polyclonal or monoclonal antibodies is now becoming commonplace in patients with renal dysfunction to delay CNI introduction, and to reduce acute rejection episodes. Biological induction agents have also permitted the use of steroid-free regimens and early reduction in CNI dose. Exploitation of the concept of liver tolerance with regimes to induce donor-specific systemic immunological tolerance by recipient pre-treatment, combined with low-dose post-transplant immunosuppression is an exciting and evolving field. Development of innovative immunotherapies that take advantage of natural immunoregulatory mechanisms contributing to immune privilege in the liver may challenge the need for lifelong immunosuppression in the future.