Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Villejuif, France.
Liver Transpl. 2011 Aug;17(8):905-13. doi: 10.1002/lt.22292.
Data on the conversion of patients to everolimus after liver transplantation are sparse. A multicenter, retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion, the employed regimens and exposure levels, and the impact on efficacy and safety. The mean time from transplantation to the introduction of everolimus was 4.9 ± 5.2 years. The mean everolimus trough level was 7.3 ± 4.1 ng/mL at month 1 and 8.1 ± 4.7 ng/mL at month 12. At 12 months, 61.6% of the patients were no longer receiving calcineurin inhibitor (CNI) therapy. The mean estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault formula was 64.2 ± 30.0 mL/minute on day 0 and 68.4 ± 32.5 mL/minute at month 12 (P = 0.007). Among patients with baseline serum creatinine levels ≥ 130 μmol/L, the eGFR values were 44.3 ± 15.7 mL/minute on day 0 and 53.7 ± 26.0 mL/minute at month 12 (P = 0.003). Four patients (1.6%) developed mild or moderate biopsy-proven acute rejection. Adverse events led to everolimus discontinuation in 12.9% of the patients. After the initiation of everolimus, the mean white blood cell count decreased significantly, and the total cholesterol and triglyceride levels increased significantly. In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus, more than 60% of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile. Randomized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted.
关于肝移植后患者转为依维莫司的相关数据较为匮乏。一项多中心、回顾性研究对 240 名接受维持性肝移植的患者进行了随访，旨在分析目前转为依维莫司的适应证、采用的方案和暴露水平，以及对疗效和安全性的影响。从移植到引入依维莫司的平均时间为 4.9 ± 5.2 年。第 1 个月和第 12 个月时，依维莫司谷浓度的平均值分别为 7.3 ± 4.1ng/mL 和 8.1 ± 4.7ng/mL。在 12 个月时，61.6%的患者不再接受钙调磷酸酶抑制剂（CNI）治疗。根据 Cockcroft-Gault 公式计算的平均估算肾小球滤过率（eGFR）在第 0 天为 64.2 ± 30.0mL/min，在第 12 个月为 68.4 ± 32.5mL/min（P=0.007）。在基线血清肌酐水平≥130μmol/L 的患者中，第 0 天的 eGFR 值为 44.3 ± 15.7mL/min，第 12 个月为 53.7 ± 26.0mL/min（P=0.003）。4 名患者（1.6%）发生了轻度或中度经活检证实的急性排斥反应。因不良事件导致 12.9%的患者停用依维莫司。依维莫司开始后，白细胞计数显著下降，总胆固醇和甘油三酯水平显著升高。在这项对最大的维持性肝移植患者队列进行的回顾性分析中，超过 60%的患者在极低的急性排斥反应风险下停用 CNI，且具有可接受的安全性。需要进行随机试验，在这些试验中，应根据临床适应证或预防性将维持性肝移植患者转为依维莫司。
