Liver Transplantation and Hepatology Unit, Hospital Universitari I Politècnic La Fe, Avda Fernando Abril Martorell, 106 (Torre F5), Valencia, 46026, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, 28029, Spain; ISS La Fe, Valencia, 46026, Spain.
University of Arizona, College of Medicine, 3110 East Minnesona Avenue, Phoenix, AZ, 85016, USA.
Best Pract Res Clin Gastroenterol. 2020 Jun-Aug;46-47:101681. doi: 10.1016/j.bpg.2020.101681. Epub 2020 Sep 11.
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.
免疫抑制（IS）药物效力的增强显著降低了肝移植（LT）中类固醇耐药排斥反应和与排斥反应相关的移植物丢失的发生率。目前，LT 后晚期死亡率的超过三分之二与移植物功能无关。然而，更有效力的 IS 药物带来的益处增加，加上移植受者的生存时间延长，导致患者更长时间接触这些药物及其不良的不良反应，形成了一把双刃剑。本文作者描述了最常用的免疫抑制药物的作用机制和不良反应，以及诱导和维持治疗中最常用的 IS 方案。在预防排斥反应的理想 IS 方案和最小化 IS 药物剂量以预防与使用相关的不良反应之间取得平衡，需要科学知识和医学艺术的经验。本文讨论了旨在保护肾功能、预防新发癌症和代谢综合征的不同方案。肝移植后晚期死亡的主要原因与 IS 药物的长期使用有关，并且有明确的证据表明肝移植受者存在过度免疫抑制。本文还回顾了 IS 最小化和停药策略的现状，评估了其益处和风险。
