Jiménez-Pérez M, González Grande R, Rando Muñoz F J, de la Cruz Lombardo J, Muñoz Suárez M A, Fernández Aguilar J L, Pérez Daga J A, Santoyo-Santoyo J, Manteca González R, Rodrigo López J M
Unidad de Hepatología-Trasplante Hepático, UGC de Aparato Digestivo, Hospital Regional Universitario de Málaga, Spain.
Unidad de Hepatología-Trasplante Hepático, UGC de Aparato Digestivo, Hospital Regional Universitario de Málaga, Spain.
Transplant Proc. 2015 Jan-Feb;47(1):90-2. doi: 10.1016/j.transproceed.2014.11.005.
The purpose of this study was to assess the efficacy and safety of a de novo immunosuppressive regimen with everolimus (EVL) plus mycophenolate mofetil (MMF) without calcineurin inhibitors (CNI) for liver transplantation. The secondary purpose was to compare the renal function with a control group of patients treated with tacrolimus plus MMF.
Sixteen male and 4 female liver transplant patients received immunosuppression with EVL plus MMF without CNI, with induction with steroids and 16 with basiliximab also. In 10 cases it was indicated as induction immunosuppression without CNI as prevention against nephrotoxicity and neurotoxicity or recurrence of hepatocarcinoma in predisposed patients and in another 10 after withdrawing CNI during the immediate post-transplant period, before hospital discharge, as the result of toxicity, mainly nephrotoxicity and neurotoxicity or the presence of hepatocarcinoma with a high risk of recurrence. A control group comprising 31 patients taking tacrolimus plus MMF was included to compare the renal function.
The mean follow-up time was 24 months. One patient had a recurrence of hepatocarcinoma at 8 months after transplant. The cases of nephrotoxicity and neurotoxicity resolved favorably. There were 7 rejections (35%); 2 evolved to chronic rejection with both needing retransplantation, 2 resolved with dose adjustment, and 3 required conversion to CNI. The side effects were hyperlipidemia (25%), wound dehiscence (10%), lymphedema (10%), cytomegalovirus infection (25%), myelotoxicity (25%) and proteinuria >1 g in 1 case (5%). No differences were found in renal function between the two groups.
This regimen was proven to be efficient to prevent and treat nephrotoxicity and neurotoxicity with an acceptable tolerability profile. However, the high associated rejection rate indicates that great caution is required in its use during the immediate post-transplant period. It is advisable to associate the regimen with low doses of CNI and to have agile methods available to monitor EVL to enable rapid dose adjustment.
本研究旨在评估采用依维莫司（EVL）联合霉酚酸酯（MMF）且无钙调神经磷酸酶抑制剂（CNI）的全新免疫抑制方案用于肝移植的疗效和安全性。次要目的是将肾功能与接受他克莫司联合MMF治疗的对照组患者进行比较。
20例肝移植患者（16例男性和4例女性）接受了EVL联合MMF且无CNI的免疫抑制治疗，其中10例采用类固醇诱导，另10例采用巴利昔单抗诱导。10例患者因预防肾毒性和神经毒性或易感患者肝癌复发而被指定为无CNI的诱导免疫抑制治疗；另外10例在移植后即刻、出院前因毒性反应（主要是肾毒性和神经毒性）或存在高复发风险的肝癌而停用CNI后接受该治疗。纳入一个由31例服用他克莫司联合MMF的患者组成的对照组以比较肾功能。
平均随访时间为24个月。1例患者在移植后8个月出现肝癌复发。肾毒性和神经毒性病例得到良好缓解。发生7次排斥反应（35%）；2例进展为慢性排斥反应，均需再次移植，2例通过调整剂量得到缓解，3例需要转换为CNI治疗。副作用包括高脂血症（25%）、伤口裂开（10%）、淋巴水肿（10%）、巨细胞病毒感染（25%）、骨髓毒性（25%），1例出现蛋白尿>1g（5%）。两组肾功能未发现差异。
该方案被证明在预防和治疗肾毒性和神经毒性方面有效，且耐受性可接受。然而，较高的相关排斥反应率表明在移植后即刻使用时需要极其谨慎。建议将该方案与低剂量CNI联合使用，并具备灵活的方法监测依维莫司以便能够快速调整剂量。
