N Engl J Med. 1994 Oct 27;331(17):1110-5. doi: 10.1056/NEJM199410273311702.
Tacrolimus (FK 506), a macrolide compound isolated from a bacterium, is a potent immunosuppressant with activity in solid-organ transplants. Most immunosuppressive regimens for liver transplantation are based on cyclosporine.
We conducted an open-label, randomized, multicenter trial to compare the efficacy and safety of tacrolimus-based and cyclosporine-based immunosuppressive regimens for patients receiving a first liver transplant. A total of 478 adults and 51 children (< or = 12 years of age) were randomly assigned at the time of transplantation to receive tacrolimus (n = 263) or cyclosporine (n = 266) and were followed for one year. The primary end points were patient and graft survival at one year. The secondary end points were the incidence of acute rejection, corticosteroid-resistant rejection, and refractory rejection (continued rejection after two courses of corticosteroids and an intervening course of muromonab-CD3).
According to Kaplan-Meier analysis, actuarial patient-survival rates at day 360 were 88 percent for both the tacrolimus and cyclosporine groups (P = 0.85; 95 percent confidence interval for the difference, -5.4 to 6.6 percent), and graft-survival rates were 82 percent and 79 percent, respectively (P = 0.55; 95 percent confidence interval for the difference, -4.8 to 9.7 percent). Acute rejection occurred in 154 patients in the tacrolimus group and 173 patients in the cyclosporine group (P < 0.002), corticosteroid-resistant rejection occurred in 43 and 82 patients, respectively (P < 0.001), and refractory rejection occurred in 6 and 32 patients, respectively (P < 0.001). Tacrolimus was associated with a higher incidence of adverse events requiring withdrawal from the study, primarily nephrotoxicity and neurotoxicity; 37 patients in the tacrolimus group and 13 in the cyclosporine group discontinued the study because of adverse events (P < 0.001).
After one year, immunosuppressive regimens based on tacrolimus and cyclosporine were comparable in terms of patient and graft survival. Tacrolimus was associated with significantly fewer episodes of acute, corticosteroid-resistant, or refractory rejection, but substantially more adverse events requiring discontinuation of the drug.
他克莫司（FK 506）是一种从细菌中分离出的大环内酯类化合物，是一种强效免疫抑制剂，在实体器官移植中具有活性。大多数肝移植免疫抑制方案都基于环孢素。
我们进行了一项开放标签、随机、多中心试验，比较以他克莫司为基础和以环孢素为基础的免疫抑制方案对首次接受肝移植患者的疗效和安全性。共有478名成人和51名儿童（≤12岁）在移植时被随机分配接受他克莫司（n = 263）或环孢素（n = 266）治疗，并随访一年。主要终点是一年时的患者和移植物存活率。次要终点是急性排斥反应、糖皮质激素抵抗性排斥反应和难治性排斥反应（在两个疗程的糖皮质激素和一个疗程的莫罗单抗-CD3干预后仍持续排斥）的发生率。
根据Kaplan-Meier分析，他克莫司组和环孢素组在第360天时的精算患者存活率均为88%（P = 0.85；差异的95%置信区间为-5.4%至6.6%），移植物存活率分别为82%和79%（P = 0.55；差异的95%置信区间为-4.8%至9.7%）。他克莫司组有154例患者发生急性排斥反应，环孢素组有173例患者发生急性排斥反应（P < 0.002），糖皮质激素抵抗性排斥反应分别发生在43例和82例患者中（P < 0.001），难治性排斥反应分别发生在6例和32例患者中（P < 0.001）。他克莫司与因不良事件而需要退出研究的较高发生率相关，主要是肾毒性和神经毒性；他克莫司组有37例患者因不良事件而停止研究，环孢素组有13例患者因不良事件而停止研究（P < 0.
