伏立康唑相关肝损伤的真实世界研究

目的：研究真实世界伏立康唑相关肝损伤的发生情况和危险因素，为临床安全用药提供参考。方法：通过信息系统提取武汉市第一医院2019年1月—2020年12月使用伏立康唑的出院患者病历，根据《药物性肝损伤诊治指南（2015年版）》对伏立康唑相关肝损伤进行回顾性分析，使用Roussel Uclaf因果关系评估法（RUCAM）评估因果关系，以国际医学组织理事会（CIOMS）的判断标准进行临床分型并进行严重程度分级，最后对发生药物性肝损伤的相关危险因素进行分析。结果：共纳入266例患者，肝损伤发生率为8.3%，多发生于用药14 d内，以肝细胞损伤型（50.0%）多见，轻、中度肝损伤占95.5%。二元Logistic回归分析显示伏立康唑谷浓度越高，肝损伤的风险越高，具有统计学意义（OR=1.607，95% CI：1.168~2.210，P=0.004），且血清白蛋白水平降低可增加伏立康唑相关肝损伤发生风险，具有统计学意义（OR=0.857，95% CI：0.754~0.975，P=0.019）。结论：伏立康唑用药期间需监护患者肝功能和血药浓度，特别是用药的前14 d和低蛋白血症患者。

Liver injury associated with voriconazole: a real-world study

OBJECTIVE To explore the incidence and risk factors of voriconazole-related liver injury in a real world to provide references for safe use of voriconazole in clinical practices.METHODS Medical records of 266 discharged patients receiving voriconazole acetate from January 2019 to December 2020 were extracted from hospital information system and voriconazole-related liver injury was retrospectively analyzed according to the Guideline of Diagnosis and Treatment of Drug-induced Liver Injury (2015). Roussel Uclaf causality assessment method (RUCAM) was utilized for evaluating the causality and clinical classifications and severity grading were performed according to the judgment criteria of International Council of Medical Organizations (CIOMS). Finally the risk factors related to drug-induced liver injury were analyzed.RESULTS The incidence of liver injury was 8.3%, occurring mostly within 14 days of medication. Hepatocyte injury (50.0%) was the most common type and mild/moderate liver injury accounted for 95.5%. Logistic regression analysis indicated that a higher voriconazole valley concentration was correlated with the risk of liver injury with statistical significance (OR=1.607, 95%CI:1.168-2.210, P=0.004). And a lower serum level of albumin increased the risk of voriconazole-related liver injury with statistical significance (OR=0.857, 95%CI:0.754-0.975, P=0.019).CONCLUSION Liver function of patients and therapeutic drug level should be monitored for patients with hypoproteinemia during the dosing of voriconazole, especially within the first 14 days.