Everson G T, Trotter J F, Kugelmas M, Forman L
Division of Gastroenterology and Hepatology and Department of Medicine, University of Colorado School of Medicine, Denver, CO 80262, USA.
Minerva Chir. 2003 Oct;58(5):725-40.
This article highlights the currently available immunosuppressive medications that are used to prevent or treat hepatic allograft rejection. Currently-available immunosuppressive medications are highly effective in prevention of allograft rejection, graft loss, and patient death. However, side effects of medications are common, usually dose-related, and specific to the administered drug. Maintenance immunosuppression which has been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or tacrolimus, Tac) is commonly modified to reduce metabolic complications of therapy. Toxic consequences of steroids may be ameliorated by steroid withdrawal without risk of acute rejection or immunologic graft loss. Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or sirolimus, and allow reduction in doses and plasma levels of CsA and Tac. Recurrence of hepatitis C is universal after liver transplantation and progresses rapidly, compared to its natural history in non-immunocompromised patients. Unfortunately, no single immunosuppressive agent or strategy has yet been shown to convincingly modify the course of post-transplant recurrence. Most centers manage recurrenc hepatitis C by either steroid avoidance, reduction in immunosuppression, or institution of antiviral therapy. Ongoing advances in immunosuppressive and antiviral medications will allow tailoring of the immunosuppressive prescription, which undoubtedly will benefit current and future liver recipients.
本文重点介绍了目前用于预防或治疗肝移植排斥反应的免疫抑制药物。目前可用的免疫抑制药物在预防移植排斥反应、移植物丢失和患者死亡方面非常有效。然而,药物的副作用很常见,通常与剂量相关,且因所使用的药物而异。主要基于钙调神经磷酸酶抑制剂(环孢素、CsA或他克莫司、Tac)的维持免疫抑制通常会进行调整,以减少治疗的代谢并发症。停用类固醇可改善其毒性后果,而不会有急性排斥反应或免疫性移植物丢失的风险。减少钙调神经磷酸酶的方案可能包括使用霉酚酸酯(MMF)或西罗莫司,并允许降低CsA和Tac的剂量及血药浓度。与非免疫受损患者的自然病程相比,肝移植后丙型肝炎复发很普遍且进展迅速。不幸的是,尚无单一的免疫抑制药物或策略能令人信服地改变移植后复发的病程。大多数中心通过避免使用类固醇、减少免疫抑制或采用抗病毒治疗来处理丙型肝炎复发。免疫抑制和抗病毒药物的不断进展将使免疫抑制方案能够个体化,这无疑将使当前和未来的肝移植受者受益。