肝移植术后他克莫司所致的肝内胆汁淤积型肝损害六例  

Intrahepatic cholestusis induced by tacrolimus after liver transplantation： a report of 6 cases

作　　者：金中奎[1] 贺强[1] 郎韧[1] 杨永久[1] 樊华[1] 寇建涛[1] 李勤涛[1] 李立新[1] 吕俊生[2] 陈大志[1] 

机构地区：[1]首都医科大学附属北京朝阳医院肝胆胰脾外科暨北京市器官移植中心肝脏移植部,北京100020 [2]中国医科大学北京顺义医院普外二科

出　　处：《中华器官移植杂志》2008年第1期28-30,共3页Chinese Journal of Organ Transplantation

摘　　要：目的探讨肝移植术后他克莫司所致的胆汁淤积型肝损害的临床特点与治疗方法。方法6例肝移植患者术后采用他克莫司（FK506）、霉酚酸酯及泼尼松预防排斥反应。术后1～3个月出现丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶及胆汁酸水平升高，并伴有明显神经症状，影像学检查提示胆管吻合口通畅，胆管未见明显狭窄及扩张，也未发现移植肝动脉病变。移植肝组织活检提示肝内胆汁淤积、胆栓形成。停用或减量使用FK506，同时行内镜下胆管内引流（ERBD）、内镜下鼻胆管引流（ENBD）、经皮经肝穿刺胆道造影（PTC）及球囊胆道扩张术引流，并辅以护肝及抗炎治疗。结果4例患者经ERBD或ENBD治疗，3个月后黄疸消退，血清转氨酶及胆管酶逐步恢复正常；1例经上述治疗3个月，未见明显好转，后行3次PTC及球囊胆道扩张术引流，于术后9个月血清转氨酶及胆管酶逐渐恢复正常，黄疸消退；1例上述治疗无效，接受再次肝移植。结论肝移植术后他克莫司所致的胆汁淤积型肝损害一般发生在用药后1～4个月，应与移植肝缺血性胆道病变相鉴别，治疗方法主要是停用或减量使用他克莫司，早期行胆道引流术，保持胆道引流通畅，并辅以护肝、抗炎等治疗。Objective To investigate the clinic characteristic and management of intrahepatic cholestasis induced by tacrolimus after liver transplantation. Methods Six recipients of liver transplantation received tacrolimus （FKS06）, mycophenolate mofetil, prednisone to prevent acute rejection. At 1st to 3rd month after operation, serum ALT, AST, ALP, γ-GT, total bile acid （TBA） were elevated and obvious neurotoxicity occurred. Image examinations showed unobstructed biliary duct, no stricture or dilation in biliary duct, and no stenosis and thrombosis in hepatic artery. Liver biopsy presented intrahepatic cholestasis and bile thrombus. In 6 patients with intrahepatic cholestasis, tacrolimus was withdrawn or its dose reduced, and at the same time, the patients received endoscopic retrograde biliary drainage （ERBD） or endoscopic nasobiliary drainage （ENBD）, percutaneous transhepatic cholangiograhy （PTC） and bile duct balloon dilatation, liver-protecting, anti-inflammation treatment. Results Four patients recovered at 3rd month after receiving ERBD or ENBD, 1 patient recovered at 9th month after 3 times of PTC and bile duct balloon dilatation, but 1 patient was subjected to retransplantation after forementioned treatment failure. Conclusion Intrahepatic cholesta- sis induced by tacrolimus after liver transplantation mostly occurs at 1st-4th month after immunosuppression, and must be differentiated from ischemic type biliary lesion of grafts. Withdrawal or reduction of tacrolimus was the main treatment.

关 键 词：肝移植 他克莫司 药物毒性 胆汁淤积 肝内 肝功能不全 

分 类 号：R657.3[医药卫生—外科学] R714.255[医药卫生—临床医学]