肝移植术后患者应用免疫抑制剂的单中心经验总结(附1400例分析)

目的总结对肝移植术后患者应用免疫抑制剂的经验,探讨个体化治疗的可行性。方法回顾分析2002年4月至2010年8月单中心1400例肝移植患者的临床资料。术后免疫抑制治疗方案的制定按时间发展经历了3个阶段:(1)第1阶段(2002年4月至2004年12月)311例患者采用传统免疫抑制治疗方案;(2)第2阶段(2005年1月至2007年12月)618例患者采用部分传统免疫抑制剂减量的方案;(3)第3阶段(2008年1月至2010年8月)471例患者采用个体化免疫抑制治疗方案。再按术前终末期肝病模型(modelforend-stageliverdisease,MELD)评分及肿瘤是否超出米兰标准分为常规组、超米兰标准组和重症组。收集3个阶段肝移植患者的生存情况,绘制生存曲线。观察第3阶段3组患者的排斥反应发生情况,了解免疫抑制剂其他不良反应及药物替换情况。结果第1、第2、第3阶段患者生存率呈逐渐升高趋势。第3阶段采用个体化治疗,3组的免疫抑制剂用量不同,但3组间免疫排斥反应发生率差异无统计学意义(均为P>0.05)。第3阶段共将12例患者的他克莫司(FK506)转换为环孢素(CsA),32例患者因肾功能损害将FK506转换为小剂量FK506+麦考酚吗乙酯(MMF)或西罗莫司,病情得以缓解。因肿瘤因素或肾功能异常应用单独应用西罗莫司27例,3例因为高脂血症或口腔溃疡不能耐受西罗莫司。结论肝移植术后免疫抑制剂的个体化治疗是可行的,可减少免疫抑制剂的用量,又不增加排斥反应发生率,有利于提高患者生存率。

Experience in a single-center with application of immunosuppressants on patients after liver transplantation: 1 400 cases analysis

Objective To sum up the experience of immunotherapy on patients after liver transplantation and to investigate the feasibility of individualized treatment.Methods Clinical data of 1 400 patients who underwent liver transplantation in a single center were analyzed retrospectively from April 2002 to August 2010.The strategies of immunosuppressive therapy after operation could be divided into 3 stages with time:(1)In stage 1(from April 2002 to December 2004),the traditional immunosuppressive treatment was used in 311 patients;(2)In stage 2(from January 2005 to December 2007),the partial decrement of immunosuppressive agents was used in 618 patients;(3)In stage 3(from January 2008 to August 2010),the individua-lized immunosuppressive treatment was used in 471 patients.And the patients were then divided into conven-tional group,outside Milan criteria group and severe patient group according to their model for end-stage liver disease(MELD)scores before transplantation and their tumor size.The survival time of all patients after liver transplantation was collected and the survival curve was drawn.The incidence of rejection of patients in 3 groups was observed.The side-effects and drug replacement of immunosuppressant were also observed.Results The survival rate of patients in stage 1,2 and 3 increased gradually.Although the immunosuppressive therapy was modified with time,there was no significant difference in the incidence of rejection among three groups(all in P> 0.05).In group 3,the immunosuppressant was changed from tacrolimus(FK506)to ciclosporin(CsA)in 12 patients.In 32 patients,the immunosuppressant was changed from FK506 to FK506 of low dosage plus mycophenolate mofetil(MMF)or sirolimus due to renal damage.And the patients recovered after drug replacement.Sirolimus was used alone in 27 patients suffered from hepatocelluar carcinoma or abnormal renal function and 3 patients could not tolerate sirolimus for hyperlipidemia or oral ulcer.Conclusions Individua-lized immunosuppressive treatment is feasible after liver transplantation.It can decrease the dosage of immunosuppressant but not increase the incidence of rejection.It is helpful to increase the survival rate of the patients.