替雷利珠单抗致肝损伤和糖尿病酮症酸中毒  

Hepatic injury and diabetic ketoacidosis induced by tislelizumab

作　　者：王雅之 段方方 李玥[1] 杨松[1] Wang Yazhi;Duan Fangfang;Li Yue;Yang Song(Center of Hepatology,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China)

机构地区：[1]首都医科大学附属北京地坛医院肝病中心,北京100015

出　　处：《药物不良反应杂志》2024年第1期50-52,共3页Adverse Drug Reactions Journal

基　　金：北京市属医院科研培育计划(PX2022071);高层次公共卫生人才培育计划(XKGG‑02030)。

摘　　要：1例63岁女性食管癌患者,既往无慢性肝病和糖尿病史,手术后接受替雷利珠单抗200 mg静脉滴注、1次/21 d单药治疗。替雷利珠单抗第4个周期治疗后39 d发现肝功能异常,丙氨酸转氨酶494 U/L,天冬氨酸转氨酶442 U/L,碱性磷酸酶1161 U/L,总胆红素21.4μmol/L。停用替雷利珠单抗。经肝脏病理学检查及相关实验室检查排除其他原因导致的肝损伤,考虑其与替雷利珠单抗有关。给予甲泼尼龙(32 mg/d口服)及保肝治疗后,患者肝功能逐渐好转。甲泼尼龙治疗2周后,减量至16 mg/d,减量2周后发现患者空腹血糖升高至19.4 mmol/L。甲泼尼龙减量至8 mg/d,2 d后血糖升至33.7 mmol/L,血乳酸3.66 mmol/L,尿酮(++++),诊断为糖尿病酮症酸中毒,停用甲泼尼龙。实验室检查示空腹和餐后血胰岛素和C肽水平明显降低,提示胰岛功能损伤,考虑为替雷利珠单抗所致的1型糖尿病。经补充胰岛素、纠正酸中毒等治疗后患者肝功能好转。8个月后随访,患者肝功能恢复正常,但需长期依赖胰岛素控制血糖。A 63‑year‑old female patient with esophageal cancer received tislelizumab monotherapy(intravenous infusion of 200 mg once every 21 days)after surgery.The patient had no disease history of chronic liver disease or diabetes mellitus.At day 39 after the fourth cycle of tislelizumab treatment,abnormalliverfunctionwasfound,withalanineaminotransferase 494 U/L,aspartateaminotransferase 442 U/L,alkaline phosphatase 1161 U/L,and total bilirubin 21.4μmol/L.Then no further tislelizumab was given.After excluding liver injury caused by other reasons through liver pathological examination and relevant laboratory tests,it was considered to be related to tislelizumab.After giving methylprednisolone(32 mg/d orally)and liver protective treatments,the patient's liver function was gradually improved.After 2 weeks of treatment,the dose of methylprednisolone was reduced to 16 mg/d,and 2 weeks later,the patient's fasting blood glucose rose to 19.4 mmol/L.The dose of methylprednisolone was reduced to 8 mg/d.After 2 days,the blood glucose rose to 33.7 mmol/L,blood lactate 3.66 mmol/L,and urinary ketone(++++).Diabetic ketoacidosis was diagnosed and methylprednisolone was discontinued.The fasting and 2‑hour postprandial serum insulin and C‑peptide levels were significantly reduced,suggesting the damage of pancreatic islet function.Type 1 diabetes caused by tislelizumab was considered.After treatments such as insulin supplement and correcting acidosis,the patient's liver function was improved.At 8 months of follow‑up,the patient's liver function returned to normal,but long‑term insulin supplement was needed to control blood glucose.

关 键 词：免疫检查点抑制剂 食管肿瘤 化学和药物性肝损伤 糖尿病酮症酸中毒 替雷利珠单抗 

分 类 号：R969[医药卫生—药理学]