Reduced-Dose Tacrolimus with Mycophenolate Mofetil vs. Standard-Dose Tacrolimus in Liver Transplantation: A Randomized Study
Reduced-Dose Tacrolimus with Mycophenolate Mofetil vs. Standard-Dose Tacrolimus in Liver Transplantation: A Randomized Study
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DOI：
10.1111/j.1600-6143.2011.03486.x
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发表时间：
2011-05-01
影响因子：
8.8
通讯作者：
Bellissant, E.
中科院分区：
文献类型：
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作者：
Boudjema, K.;Camus, C.;Bellissant, E.
我们在肝移植中进行了一项多中心随机研究，比较标准剂量他克莫司与减剂量他克莫司联合霉酚酸酯，以减少他克莫司副作用的发生。在移植后48周内监测两个主要结局（审查标准）：肾功能障碍或动脉高血压或糖尿病的发生（评估获益）和急性移植排斥反应的发生（评估风险）。在移植排斥风险增加的情况下，每40例患者进行中期分析以停止研究。研究停止时纳入了195例患者（对照组100例，实验组95例）。对照组和实验组分别有46例（46%）和28例（30%）患者发生急性移植排斥反应（HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024）。对照组和实验组分别有80例（80%）和61例（64%）患者出现肾功能不全或动脉高血压或糖尿病（HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021）。对照组和实验组分别有42例（42%）和23例（24%）患者出现肾功能不全（HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004）。白细胞减少症（p = 0.001）、血小板减少症（p = 0.017）和腹泻（p = 0.002）在实验组发生率更高。小剂量他克莫司联合霉酚酸酯可减少肾功能障碍的发生和移植物排斥反应的风险。这种免疫抑制方案可替代全剂量他克莫司用于成人肝移植。
We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.