【作者】 谢琴芬；

【导师】 郑树森；

【作者基本信息】 浙江大学 ， 外科学， 2010， 硕士

【摘要】 背景：肝移植是治疗终末期肝病的唯一有效手段。霉酚酸酯(Mycophenolate mofetil, MMF)作为无肾毒性的免疫抑制剂在肝移植术后广泛应用,但它存在骨髓抑制,胃肠道反应等副作用,使得临床上存在一部分肝移植受者不能耐受MMF治疗。本研究通过分析临床上因不耐受MMF而未使用MMF的肝移植受者术后并发症发生及转归情况,总结出MMF不耐受病人的免疫抑制方案使用经验。方法：我院从2008年1月至2009年12月间共施行肝移植手术188例,其中采用他克莫司(FK506)联合激素或不联合激素免疫抑制方案的病例24例为无MMF组；对照组选择同期手术并与实验组在年龄、性别、随访时间等相匹配的48例病例,为MMF组,均采用他克莫司+MMF+激素三联或他克莫司+MMF二联方案。比较两组间肝移植术前资料及术后并发症的发生情况。结果：无MMF组和MMF组肝移植受者术后平均随访时间分别为12.4月和14.0月。无MMF组病人术前白细胞、血红蛋白、血小板水平显著低于MMF组病人,分别为(2.1±0.9)*109/L vs.(5.5±3.3)*109/L,P<0.01；93±23g/L vs.106±27g/L,P=0.041；(38±21)*109/L vs.(84±66)*109/L,P<0.01)。无MMF组的FK506血药浓度在移植术后2d、1周、2周、3周、4周与MMF组相比无明显统计学差异(P>0.05)。发生急性排斥时无MMF组FK506血药浓度与MMF组相比无显著性差异(5.54±1.96 ng／ml vs.6.76±1.84 ng／ml,P>0.05)。在急性排斥反应发生率上,无MMF组显著高于MMF组(45.8% vs.14.6%,P=0.004)；在经肝穿证实的急性排斥反应发生率上,无MMF组与MMF组相比在统计学上无显著性差异(25%vs.10.6%,P=0.105),且无MMF组63.6%为轻型容易控制的急性排斥反应。无MMF组和MMF组在移植术后感染发生率(62.5% vs.43.8%,P=0.134)高血压病发生率(8.3%vs.8.7%,P=0.959),糖尿病发生率(13% vs.4.5%,P=0.209),肝癌复发率(27.3% vs.38.5%,P=0.562),乙肝复发率(0%vs.4.2%,P>0.05)及患者生存率(100% vs.93.8%,P>0.05)在统计学上并无显著差异。结论：对于MMF不耐受的肝移植受者,无MMF免疫抑制方案可增加轻型急性排斥反应的发生,但不影响肝移植受者术后感染、代谢并发症、肝癌复发、乙肝复发的发生及患者生存率,因而是安全可行的。更多还原

【Abstract】 Background:Liver transplantation is the only effective method to treat end-stage liver disease. As a non-nephrotoxic immunosuppressant following liver transplantation, mycophenolate mofetil(MMF) possesses side effects such as bone marrow suppression, and gastrointestinal disorders, resulting in the existence of patients who are intolerant of MMF. This study aims to explore the complications and outcome of MMF-intolerant patients treated with MMF-free immunosuppressive regimens after liver transplantation, and summarizes a single center experience in application of immunosuppressive regimens in MMF-intolerant liver transplant recipients.Methods:Altogether 188 patients undergoing liver transplantation from January 2008 to December 2009 were reviewed. The preoperative data and postoperative complication rates were compared between MMF-free group (24 cases, tacrolimus(FK506)+steroid or FK506 regimen without steroid) and MMF group (48 cases, FK506+MMF+steroid or FK506+MMF regimen) as a control. Results:The mean follow-up time for liver transplant recipients in MMF-free group and MMF group was 12.4 and 14.0 months, respectively. Preoperative levels of white blood cell, hemoglobin and platelet in MMF-free group were significantly lower than that in the MMF group, respectively (2.1±0.9)*109/Lvs.(5.5±3.3)*109/L,P<0.01; 93±23g/L vs.106±27g/L, P=0.041; (38±21)*109/L vs.(84±66)*109/L, P<0.01). There was no significant difference between MMF-free group and MMF group in blood concentration of FK506 at 2nd day,1st week,2nd week,3rd week and 4th week after liver transplantation (P> 0.05). When acute rejection occurs, there was no significant difference in the blood concentration of FK506 between MMF-free group and MMF group (5.54±1.96 ng/ml vs.6.76±1.84 ng/ml, P>0.05). The incidence of acute rejection in MMF-free group was significantly higher than that in MMF group (45.8% vs.14.6%, P=0.004). The incidence of biopsy-proven acute rejection in MMF-free group was higher than that in MMF group (25% vs.10.6%), but the difference was not statistically significant (P=0.105), and about 63.6% acute rejection types in MMF-free group are considered to be mild rejection easy to be controlled. There was no significant difference between MMF-free group and MMF group in the rates of infection (62.5% vs. 43.8%, P=0.134), hypertension (8.3% vs.8.7%, P=0.959), diabetes (13% vs.4.5%, P=0.209), tumor recurrence (27.3% vs.38.5%, P=0.562), hepatitis B recurrence (0% vs.4.2%, P> 0.05) and patient survival (100% vs.93.8%, P> 0.05).Conclusion:For liver transplant recipients who are intolerant of MMF, MMF-free immunosuppressive regimen may increase the incidence of mild acute rejection,but does not affect infection, metabolic complications, tumor recurrence, HBV recurrence and patient survival after liver transplantation, so it is considered to be safe and feasible.更多还原