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

doi:10.3969/j.issn.2095-1264.2024.01.21

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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
DOI:
                        10.3969/j.issn.2095-1264.2024.01.21
                    
作者:
                        
                        
                    
作者单位: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
作者简介:钟宇科，主管药师，研究方向：临床药学（抗肿瘤）。
通讯作者:谢聪，博士，主管药师，研究方向：临床药学。
中图分类号:R969.3
基金项目:

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

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Affiliation:

1.Department of Pharmacy, Shenzhen Longgang Central Hospital, Shenzhen, 518116, Guangdong, China;2.Department of Pharmacy, the Sixth People's Hospital of Huizhou, Huizhou, 516211, Guangdong, China;3.Department of Pharmacy, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China

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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。

Abstract:

Objective To report the clinical characteristics of severe hepatotoxicity due to PD-1 inhibitors and the safety 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 hepatocellular injury type, and some presenting as a mixed type. Ten patients recovered after hepatotoxicity. Only five patients challenged the PD-1 inhibitors again. Three of them suffered from hepatotoxicity again. Two of the three patients suffered from severe hepatotoxicity, resulting in permanent withdrawal of PD-1 inhibitors, and they had a different type of hepatotoxicity 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 underwent rechallenge with PD-1 inhibitors, and a significant proportion of them experienced a severe recurrence of hepatotoxicity.