三唑类抗真菌药相关肝损伤不良事件监测及风险因素分析

Monitoring of adverse events and risk factors of liver injury related to triazole antifungal drugs

目的探讨在住院患者中三唑类抗真菌药相关肝损伤不良事件的发生率及危险因素。方法依托医疗机构药物不良事件主动监测与智能评估警示系统(ADE-ASAS),回顾性收集本院自2010年1月至2021年6月间所有符合要求的使用三唑类抗真菌药注射制剂的住院患者病例资料,并根据用药情况将其分为伏立康唑、氟康唑、伊曲康唑3组,分析各组的肝损伤不良事件的发生率及危险因素。结果共纳入555例阳性病例,肝损伤不良事件总发生率为5.31%,其中,伏立康唑组、氟康唑组、伊曲康唑组的发生率分别为6.53%、4.52%和4.53%。伏立康唑致肝损伤不良事件的危险因素为造血干细胞移植、低白蛋白、高总胆红素基值、联合使用烷化剂;氟康唑致肝损伤不良事件的危险因素为造血干细胞移植、低白蛋白、高总胆红素基值、手术治疗;伊曲康唑致肝损伤不良事件的危险因素为造血干细胞移植、低白蛋白。结论三唑类抗真菌药相关肝损伤属常见药物不良反应,临床使用三唑类抗真菌药时,对住院期间行造血干细胞移植、外科手术治疗的患者以及合并有低白蛋白血症、高总胆红素基值、联合使用烷化剂的患者,应密切关注其肝功能。

Objective To investigate the incidence and risk factors of adverse events related to liver injury induced by triazole antifungal agents in inpatients.Methods Based on the active Surveillance and Intelligent Assessment alert System of Adverse Drug Events in medical institutions(ADE-ASAS),all eligible inpatients who received triazole antifungal injective preparation from January 2010 to June 2021 were retrospectively studied and divided into voriconazole,fluconazole and itraconazole groups,and the incidence and risk factors of liver injury in each group were analyzed.Results A total of 555 positive cases were included,and the overall incidence of adverse events of liver injury was 5.31%,among which,the incidence of voriconazole,fluconazole and itraconazole were 6.53%,4.52%and 4.53%,respectively.The risk factors for adverse events of liver injury caused by voriconazole were hematopoietic stem cell transplantation,hypoalbuminemia,high baseline of total bilirubin(TB)and combined use of alkylation agents.the risk factors of fluconazole-induced liver injury adverse events were hematopoietic stem cell transplantation,hypoalbuminemia,high baseline of TB,surgical trea tm ent.The risk factors of liver injury induced by itraconazole included hematopoietic stem cell transplantation and hypoalbuminemia.Conclusion Triazole antifungal drug-related liver injury is a common adverse drug reaction.When triazole antifungal agents are used clinically,the liver function of patients undergoing hematopoietic stem cell transplantation or surgical treatment during hospitalization,as well as patients with hypoalbuminemia,high baseline of TB and combined use of alkylating agents should be closely monitored.