PD-1抑制剂引起的严重肝损伤及肝损伤后再挑战的病例系列报道  

Clinical characteristics of severe hepatotoxicity induced by PD-1 inhibitors and rechallenge after hepatotoxicity:a case series report

作　　者：钟宇科 刘文新 谢聪 ZHONG Yuke;LIU Wenxin;XIE Cong(Department of Pharmacy,Shenzhen Longgang Central Hospital,Shenzhen,518116,Guangdong,China;Department of Pharmacy,the Sixth People's Hospital of Huizhou,Huizhou,516211,Guangdong,China;Department of Pharmacy,Nanfang Hospital of Southern Medical University,Guangzhou,510515,Guangdong,China)

机构地区：[1]深圳市龙岗中心医院药剂科,广东深圳518116 [2]惠州市第六人民医院药剂科,广东惠州516211 [3]南方医科大学南方医院药学部,广东广州510515

出　　处：《肿瘤药学》2024年第1期126-132,共7页Anti-Tumor Pharmacy

摘　　要：目的报告程序性死亡受体1(PD-1)抑制剂所致严重肝损伤的临床特征及肝损伤后再挑战的安全性。方法对接受PD-1抑制剂治疗的641例肿瘤患者进行回顾性调查。结果641例患者中共有10例患者(1.56%)出现严重肝损伤,中位发生时间为53(1~265)d,中位转归时间为25(3~56)d。肝损伤类型主要表现为肝细胞损伤型,部分表现为混合型。10例患者均出现转归,其中5例接受了再挑战。3例患者经历了肝毒性复发,其中2例因严重肝毒性复发而永久性停药,2例患者的肝损伤类型与上次不同。结论PD-1抑制剂引起的严重肝损伤预后较好,但最终可能导致大多数患者永久性停用PD-1抑制剂。半数患者接受了PD-1抑制剂再挑战,其中相当一部分患者经历了严重的肝毒性复发。Objective To report the clinical characteristics of severe hepatotoxicity due to PD-1 inhibitors and the safe-ty of rechallenge after hepatotoxicity.Methods A retrospective survey of 641 cancer patients treated with PD-1 inhibitors was conducted.Results Totally 10 out of the 641 patients(1.56%)developed severe hepatotoxicity,with a median time to onset of 53 d(1~265 d)and a median time to regression of 25 d(3~56 d).The type of hepatotoxicity was predominantly he-patocellular injury type,and some presenting as a mixed type.Ten patients recovered after hepatotoxicity.Only five pa-tients challenged the PD-1 inhibitors again.Three of them suffered from hepatotoxicity again.Two of the three patients suf-fered from severe hepatotoxicity,resulting in permanent withdrawal of PD-1 inhibitors,and they had a different type of hep-atotoxicity from the previous one.Conclusion Severe hepatotoxicity caused by PD-1 inhibitors has a good prognosis but eventually leads to permanent discontinuation of PD-1 inhibitors in most patients.In addition,half of the patients under-went rechallenge with PD-1 inhibitors,and a significant proportion of them experienced a severe recurrence of hepatotoxici-ty.

关 键 词：PD-1抑制剂 免疫治疗相关肝炎 再挑战 

分 类 号：R969.3[医药卫生—药理学]