Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
Panminerva Med. 2009 Dec;51(4):215-25.
A significant increase of potent immunosuppressive agents over the last two decades has contributed to improved patient and graft survival after liver transplantation (LT). Numerous ongoing studies aim to determine the most effective immunosuppressive protocols while minimizing drug-related side effects. These protocols often combine several drugs with different mechanisms of action and toxicities allowing dosage adjustment. There is also a trend towards tailored immunosuppressive regimens according to the etiology of liver disease and comorbidities such as renal dysfunction and cardiovascular disease. The introduction of antibody induction therapies and antimetabolites resulted in an increasing number of studies with steroid minimization and calcineurin inhibitor (CNI) reduction protocols. Combined mycophenolate mofetil and minimal dose CNI therapy has shown to be safe and to improve kidney function and cardiovascular risk profile in the majority of studies. Sirolimus (SRL) and everolimus constitute a new class of compounds designated as the mammalian target of rapamycin (mTOR) inhibitors, which exhibit immunosuppressive and antiproliferative effects. There are conflicting results with respect to renal improvement upon switch to mTOR inhibitor therapy with concomitant reduction/elimination of CNI. Further trials will determine whether earlier conversion to mTOR inhibitors enable prevention of CNI-related renal dysfunction. Future results from randomized controlled studies will also show whether SRL can improve recurrence-free survival in patients transplanted for hepatocellular carcinoma.
在过去的二十年中，强效免疫抑制剂的大量使用促进了肝移植（LT）后患者和移植物的存活率的提高。许多正在进行的研究旨在确定最有效的免疫抑制方案，同时最大限度地减少药物相关的副作用。这些方案通常结合几种具有不同作用机制和毒性的药物，允许调整剂量。根据肝脏疾病的病因和合并症（如肾功能不全和心血管疾病）制定个体化免疫抑制方案也成为一种趋势。抗体诱导治疗和抗代谢药物的引入导致越来越多的研究采用类固醇最小化和钙调神经磷酸酶抑制剂（CNI）减少方案。联合霉酚酸酯和最小剂量 CNI 治疗已被证明是安全的，并能改善大多数研究中的肾功能和心血管风险状况。西罗莫司（SRL）和依维莫司是一类被称为雷帕霉素哺乳动物靶标（mTOR）抑制剂的新型化合物，具有免疫抑制和抗增殖作用。关于转换为 mTOR 抑制剂治疗同时减少/消除 CNI 后肾功能改善的结果存在争议。进一步的试验将确定是否早期转换为 mTOR 抑制剂可以预防 CNI 相关的肾功能障碍。随机对照研究的未来结果还将表明 SRL 是否可以改善因肝细胞癌而接受移植的患者的无复发生存率。
