阿兹夫定片治疗新型冠状病毒肺炎引起药物性肝损伤真实世界研究  

A real-world study of azivudine tablets for drug-induced liver injury caused by novel coronavirus pneumonia

作　　者：刘秀珍[1] 刘建军[1] 方兴[1] 李萌[2] 赵晶晶[2] 邢海燕[1] LIU Xiuzhen;LIU Jianjun;FANG Xing;LI Meng;ZHAO Jingjing;XING Haiyan(Department of Pharmacy,Second Municipal People's Hospital,Anhui Hefei 23000,China;Department of Critical Care Medicine,Second Municipal People's Hospital,Anhui Hefei 23000,China)

机构地区：[1]合肥市第二人民医院,药学部,安徽合肥230000 [2]合肥市第二人民医院,重症医学科,安徽合肥230000

出　　处：《中国医院药学杂志》2024年第9期1082-1087,共6页Chinese Journal of Hospital Pharmacy

基　　金：安徽省高等学校科学研究项目(自然科学类)(编号:2022AH050712)。

摘　　要：目的:探究真实世界阿兹夫定片治疗新型冠状病毒肺炎(COVID-19)引起药物性肝损伤(drug-induced liver injury,DILI)发生情况和危险因素,为临床安全用药提供参考。方法:回顾性收集2022年11月30日至2023年1月26日于合肥市第二人民医院住院期间服用阿兹夫定片治疗COVID-19患者病历,记录每位患者年龄、性别、体质量、用药剂量、治疗疗程、合并用药情况、肝功能指标、药物肝损不良反应等信息,统计阿兹夫定发生DILI的基本特征;并将患者分为未发生DILI组和发生DILI组,比较两组患者基本特征和药物治疗的差异,进一步探讨阿兹夫定引起DILI的影响因素。结果:共纳入符合条件的患者294例,发生DILI为17例,占比5.78%;DILI临床分型方面,肝细胞损伤型4例,胆汁淤积型6例,混合型7例;DILI因果关系评估方面,17例DILI中极可能1例,很可能12例,可能4例;DILI严重程度分级方面,17例患者中轻度肝损伤(1级)10例,中度肝损伤(2级)5例,2例患者由于检测数据不全而未分级;DILI发生时间方面,17例患者阿兹夫定平均用药疗程为(7.6±3.7)d,DILI发生时间为服药后的(6.4±3.9)d。影响因素方面,合并用药数量、低蛋白血症、危重患者是发生DILI的显著影响因素(P<0.05)。结论:阿兹夫定治疗COVID-19引起的DILI为临床常见不良反应,严重程度方面多为轻、中度不良反应,临床使用总体安全性和耐受性良好;临床使用前应评估患者病理状态,对于合并低蛋白血症和/或危重患者,应进行全面评估后谨慎用药;使用过程中应尽量减少合并用药数量,特别是避免与其有相互作用的药物联合使用,以此避免DILI的发生。OBJECTIVE To explore the occurrences and risk factors of drug-induced liver injury(DILI)caused by azivudine tablets for corona virus disease 2019(COVID-19)in real world and provide references for safe clinical dosing.METHODS From November 30,2022 to January 26,2023,medical records were retrospectively reviewed for 294 hospitalized patients taking azivudine tablets for COVID-19.Age,gender,weight,dosage,course of treatment,co-medication,liver function parameters and adverse reactions of causing liver injuries were recorded.Basic characteristics of azvudine DILI were examined.They were assigned into two groups of non-DILI and DILI.The inter-group differences of basic characteristics and medications were compared and the influencing factors of azivudine-induced DILI further discussed.RESULTS Among them,17 cases(5.78%)developed DILI.In clinical classification of DILI,the types were hepatocyte injury(n=4),cholestasis(n=6)and mixed(n=7).Regarding DILI causality assessment,the likelihood was extreme(n=1),quite(n=12)and possible(n=4).As for DILI severity,the grade wasⅠ(mild,n=10),Ⅱ(moderate,n=5)and unknown(n=2).As for occurrence time of DILI,average treatment duration of azvudine was(7.6±3.7)days and occurrence time of DILI(6.4±3.9)days post-dosing.Number of co-medications,hypoproteinemia and critical illness were significant influencing factors for the development of DILI(P<0.05).CONCLUSION DILI induced by azivudine for COVID-19 is a common clinical adverse reaction.Most adverse reactions are mild or moderate in severity.The overall safety and tolerability of azivudine are decent in clinical practices.The pathological status of patients should be evaluated prior to clinical dosing.For individuals with hypoproteinemia and/or critically illness,azivudine should be carefully dosed after comprehensive evaluations.During dosing,the number of co-medications should be minimized,especially interacting co-medications should be avoided to avoid the occurrence of DILI.

关 键 词：阿兹夫定片 新型冠状病毒肺炎 药物性肝损伤 

分 类 号：R978.7[医药卫生—药品]