PD-1抑制剂用于肝癌肝移植术前治疗的安全性探讨  

Safety of PD-1 inhibitor in preoperative treatment of liver transplantation for liver cancer

作　　者：刘召波[1] 武聚山[1] 林栋栋[1] 栗光明 Liu Zhaobo;Wu Jushan;Lin Dongdong;Li Guangming(General Surgery Center,Beijing You'an Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院普通外科中心,100069

出　　处：《器官移植》2021年第4期445-449,共5页Organ Transplantation

基　　金：北京医卫健康公益基金会医学科学研究基金(LC19003);北京市医院管理中心重点医学专业发展计划——肝脏外科专业(ZYLX202124)。

摘　　要：目的探讨程序性细胞死亡蛋白1(PD-1)抑制剂用于原发性肝癌(肝癌)肝移植术前治疗的安全性。方法回顾性分析7例术前应用PD-1抑制剂的肝癌肝移植受者的临床资料,总结受者免疫相关不良反应(irAE)发生情况及预后情况,评估PD-1抑制剂在肝癌肝移植受者中使用的安全性。结果 7例肝癌肝移植受者术前使用PD-1抑制剂,使用疗程为1~20个,自停药至手术间隔时间为6~120 d。5例受者发生不同程度的irAE,其中疲乏3例、发热2例、脱发2例、皮疹2例、腹泻1例、恶心1例、心肌炎1例,多数irAE毒性分级为G1~2级,1例发生G5级毒性反应(致死性心肌炎),并导致受者死亡。1例受者于术后7 d发生排斥反应,经糖皮质激素冲击治疗及增加他克莫司剂量后好转。结论 PD-1抑制剂可用于肝癌肝移植术前治疗,但应密切注意其irAE及术后排斥反应的发生。Objective To evaluate the safety of programmed cell death protein 1(PD-1)inhibitor in the treatment of primary liver cancer(liver cancer)before liver transplantation.Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed.The incidence of immune-related adverse event(irAE)and clinical prognosis of the recipients were summarized.The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated.Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer.The time interval from drug withdrawal to liver transplantation was 6-120 d.Five recipients suffered from irAE of different degrees,including fatigue in 3 cases,fever in 2 cases,alopecia in 2 cases,rash in 1 case,nausea in 1 case and myocarditis in 1 case,respectively.A majority of these irAE were classified as grade-.One recipient died from grade irAE(fatal myocarditis).One recipient developed rejection at postoperative 7 d,which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus.Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer.Nevertheless,the incidence of irAE and postoperative rejection should be intimately monitored.

关 键 词：肝移植 免疫检查点抑制剂 程序性细胞死亡蛋白1抑制剂 原发性肝癌 免疫相关不良反应 排斥反应 纳武单抗 信迪利单抗 帕博利珠单抗 卡瑞利珠单抗 

分 类 号：R617[医药卫生—外科学] R575[医药卫生—临床医学]