摘要
目的观察以他克莫司(FK506)为基础的免疫抑制方案在肝移植后合理的联用方法及合适的血药浓度。方法本实验为单中心、随机、开放、前瞻性研究。从2001年2月至2004年7月首次肝移植患者94例,初始给予以他克莫司为基础的免疫抑制方案治疗(二联:联用糖皮质激素;三联:联用麦考吗替酚酯(MMF)+糖皮质激素;四联:联用MMF+糖皮质激素,用2个剂量赛尼哌诱导治疗),比较术后6个月各组之间的有效性与安全性。结果术后6个月内急性排斥反应率:二联25·9%,三联11·1%,四联7·5%;二联组与四联组比差异有显著性(P=0·038)。术后6个月人/肝存活率相同,分别为:二联88·9%,三联92·6%,四联92·5%,P=0·67。高血压发病率分别为:二联37·0%,三联18·52%,四联17·50%,P=0·834。高血糖发病率分别为:二联40·7%,三联33·3%,四联35·0%,P=0·573。手震颤发病率分别为:二联59·3%,三联51·9%,四联47·5%,P=0·639。乙肝再感染率分别为:二联12·0%,三联19·2%,四联7·9%,P=0·339;CMV感染率分别为:二联55·6%,三联59·3%,四联67·5%,P=0·586;细菌感染率分别为:二联48·2%,三联44·4%,四联55%,P=0·680。在术后3个月谷氨酸转氨酶(ALT)水平分别为:二联:64·0±50·9,三联:29·3±23·0,四联:30·00±37·4,P=0·030;四联比二联显著低,P=0·011。血胆固醇(Tch)水平分别为:二联:5·24±1·17,三联:4·70±1·06,四联:4·36±1·09,P=0·005;四联组比二联组显著低,P=0·002。结论以他克莫司为基础的免疫抑制方案应选择低剂量联合应用对移植肝有较好的保护作用,减低对机体的毒副作用。
Objective To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus. Methods Ninety-four adult recipients of cadaveric livers were randomly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens ： dual （ tacrolimus ＋ glucocorticoid）, triple [ tacrolimus ＋ mycophenolate mofetil （MMF） ＋ glucocorticoid ]; quadruple [ tacrolimus ＋ MMF ＋ glucocorticoid in addition of induction treatment by daclizumab ]. The efficacy and safety of the 3 groups 6 months after the transplantation were compared. Results The frequencies of acute rejection were 25.9%, 11.1%, and 7.5% for the dual, triple, and quadruple therapy groups, that of the quadruple therapy group being significantly lower than that of the dual therapy group （ P = 0. 038 ）. There were no significant differences in the rates Three months after transplantation, the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group （ PALT = 0.011, PTch = 0. 002 ）. Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng · ml^-1 - 13 ng · ml^-1. Conclusions Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest, followed by the triple therapy and dual therapy. Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2006年第48期3389-3392,共4页
National Medical Journal of China
基金
国家"973"重点基础研究发展计划基金资助项目(2003CB515501)
关键词
他克莫司
肝移植
免疫抑制剂
急性排斥反应
Tacrolimus
Liver transplantation
Immunosuppression
Acute rejection
