西罗莫司与他克莫司对超米兰标准肝癌患者肝移植后肿瘤复发的影响

Impact of sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond milan criteria： randomized controlled clinical trial

目的探讨西罗莫司与他克莫司对超米兰标准原发性肝癌患者肝移植后肿瘤复发的影响。方法采用区组随机法将2008年1月至2012年4月间接受肝移植治疗的超米兰标准的原发性肝癌患者61例分为西罗莫司组（30例）和他克莫司组（31例）。他克莫司组采用以他克莫司为基础的免疫抑制方案，皮质激素仅用1个月，视情况使用吗替麦考酚酯，但用量不超过1．5g／d。西罗莫司组术后1个月内的免疫抑制方案同他克莫司组，术后1个月开始将他克莫司分步转换为西罗莫司。肿瘤复发或转移前不采取抗肿瘤措施。有复发或转移之后，依具体情况进行肿瘤局部治疗和（或）全身药物治疗。比较两组受者肿瘤复发率和受者存活率。结果术后随访时间为10．3～60．2个月，中位数为35．2个月。西罗莫司组术后1、2、3和4年肿瘤复发率分别为13．3％、36．7％、43．3％和53．3％，均显著低于他克莫司组（38．7％、67．7％、74．2％和77．4％），差异均有统计学意义（P〈0．05）。西罗莫司组的受者1年存活率为90．O％，他克莫司组为87．1％（P〉O．05），但西罗莫司组的2、3和4年受者存活率（53．3％、33．3％和20．O％）均显著高于他克莫司组（41．9％、22．6％和9．7％），差异均有统计学意义（P〈0．05）。两组间肝、肾功能异常发生率的差异无统计学意义（P〉0．05）。结论与他克莫司相比，西罗莫司能显著降低超米兰标准原发性肝癌患者肝移植后的肿瘤复发率，提高受者的存活率。

Objective To compare the impact of the sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond Milan criteria. Method Sixty-one liver transplantation recipients due to HCC beyond Milan criteria, between Jan. 2008 and Apri. 2012, were randomized, with the informed consent, into two different immunosuppression groups： sirolimus group （n = 30） and tacrolimus group （n = 31）. In tacrolimus group, tacrolimus was used as the basic immunosuppressant, methylprednisolone was discontinued within one month postoperatively, and myeophenolate mofetil was used within the dosage of 1.5 g/d accordingly. In sirolimus group, the immunosuppresive scheme was the same as that of the tacrolimus group within postoperative one month, and from that, tacrolimus was transferred to sirolimus. No antineoplastic agents were given before tumor recurrence. The tumor recurrence rate and the survival rate of the recipients were compared between the two groups. Result The median follow-up duration was 35. 2 months （10. 3 -60. 2）. The tumor recurrence rate at postoperative year 1, 2, 3 and 4 in the sirolimus group （13. 3%, 36.7%, 43.3% and 53.3%） was significantly lower than that in the tacrolimus group （38. 7%, 67. 7%, 74. 2% and 77. 4% ）, P 〈 0. 05 for all. The one-year survival rate in the recipients postoperation had no significant difference between sirolimus group and tacrolimus group （90. 0% vs. 87. 1%, P = 0. 438）. The 2-, 3- and 4-year survival rate in the recipients was significantly higher in the sirolimus group （53. 3%,33. 3% and 20. 0%） than that in the tacrolimus group （41.9%, 22. 6% and 9. 7% ）, P 〈 0. 05 for all. The liver function and renal function of the recipients at the postoperative year 1, 2, 3 and 4 showed no significant difference between the two groups, P〉0. 05. Conclusion In comparison with tacrolimus, sirolimus could significantly reduce the tumor recurrence rate and increase the survival rate for the liver transplant recipients due to HCC beyond Milan criteria.