肝移植术后存活十年以上患者他克莫司治疗随访报告

摘要

Objective To study the tacrolimus plasma concentration in liver transplant recipients who survived for ten years or more and to correlate with the occurrence of rejection,metabolic complications and renal insufficiency.Methods A retrospective study was conducted on 129 patients who received orthotopic liver transplantation (OLT) before September 2003 and who were still alive in September 2013.These patients received prolonged tacrolimus only for immunosuppression,and they did not receive any renal transplantation.The underlying occurrence of rejection,metabolic complications and renal insufficiency were analyzed.Results The results showed the tacrolimus plasma concentration rapidly decreased from (7.3 ± 3.1) ng/ml in the first three months of liver transplantation to (4.0 ± 2.1) ng/ml in the fourth year.A plateau then followed from the fourth year to the seventh year,in which the concentration was maintained at (4.1 ± 2.1) ng/ml.This was followed by another plateau between the eighth year and the eleventh year,with a maintenance concentration of (3.4 ± 1.5) ng/ml.Rejection was observed in 17 patients (rate 13.2％).In 13 patients (72.2％) the rejection occurred in the first year.The two peak periods for metabolic complications and renal insufficiency to occur were within the first three months and between the fifih to the tenth year.New-onset diabetes (57 cases,44.2％) was most common followed by new-onset hypertension (39 cases,30.2％),new-onset hyperlipemia (31 cases,24.0％),and new-onset renal insufficiency (20 cases,15.5％).Conclusions Clinicians should be very cautious in maintaining tacrolimus plasma concentration over time.Rejection occurred more commonly within the first year postoperatively.More attentions should be paid on metabolic complications and renal insufficiency in the first three years and from the fifth year onwards after liver transplantation.%目的 分析肝移植术后存活十年以上患者他克莫司(Tac)血药浓度维持情况以及排斥反应、代谢性疾病和肾功能不全发生情况,为临床提供参考.方法 回顾性分析2003年9月前首次肝移植存活至2013年9月、未行肾移植、术后长期单一服用Tac的129例成人患者的临床资料,总结Tac血药浓度维持情况,统计该浓度水平下排斥反应、术后新发代谢性并发症和新发肾功能不全的发生情况.结果 患者资料分析显示移植术后前4年Tac血药浓度处于快速下降期,由最初3个月的(7.3±3.1) ng/ml,降至术后第4年的(4.0±2.1)ng/ml;术后第5年至7年进入第1个平台期.此期间Tac血药浓度维持在(4.1±2.1)ng/ml;术后第8年至11年进入第2个平台期,此期间Tac血药浓度维持在(3.4 ± 1.5) ng/ml.随访期间,共17例患者发生排斥反应,排斥反应发生率为13.2％.术后1年内为排斥反应高发期,共发生13例次(72.2％).肝移植术后代谢紊乱肾功能不全经历术后3个月内及术后第5年至第10年两个发病高峰.代谢紊乱以新发糖尿病(57例,44.2％)为主,其余依次为新发高血压39例(30.2％)、新发高脂血症31例(24.0％)、新发肾功能不全20例(15.5％).结论 随着肝移植术后时间的延长,Tac血药浓度的维持应更加慎重.肝移植术后一年内应警惕排斥反应的发生.术后3个月以及从术后第5年开始临床应严密监测患者代谢性并发症和肾功能不全的发生情况并予及时治疗.