慢性药物性肝损伤的临床特征:一项多中心、回顾性横断面研究  

Clinical characteristics of chronic drug‑induced liver injury:a multicenter retrospective cross‑sectional study

作　　者：赵红[1] 刘映霞[2] 谢青[3] 李军 阎明[5] 许建明[6] 刘家俊[7] 窦晓光[8] 陈成伟 茅益民 谢雯[1] Zhao Hong;Liu Yingxia;Xie Qing;Li Jun;Yan Ming;Xu Jianming;Liu Jiajun;Dou Xiaoguang;Chen Chengwei;Mao Yimin;Xie Wen(Liver Disease Center,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Depart-ment of Hepatology,the Third People′s Hospital of Shenzhen,Guangdong Province,Shenzhen 518112,China;Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Infectious Diseases,Jiangsu Province Hospital,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Geriatric Gastroenterology,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Gastroenterology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Infectious Diseases,the First Affiliated Hospital of Xiamen University,Fujian Province,Xiamen 361003,China;Department of Infectious Diseases,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of Hepatology,the 905th Hospital of PLA Naval Affiliated to Naval Medical University,Shanghai 200052,China;Department of Digestive Diseases,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Institute of Digestive Diseases,Shanghai Fatty Liver Disease Diagnosis and Treatment Research Center,Shanghai 200025,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 [2]深圳市第三人民医院肝病科,深圳518112 [3]上海交通大学医学院附属瑞金医院感染科,上海200025 [4]江苏省人民医院(南京医科大学第一附属医院)感染科,南京210029 [5]山东大学齐鲁医院老年消化科,济南250012 [6]安徽医科大学第一附属医院消化内科,合肥230022 [7]厦门大学第一附属医院感染科,厦门361003 [8]中国医科大学附属盛京医院感染科,沈阳110004 [9]中国人民解放军海军第九〇五医院肝病科,上海200052 [10]上海交通大学医学院附属仁济医院消化内科/上海市消化疾病研究所/上海市脂肪性肝病诊治研究中心,上海200025

出　　处：《药物不良反应杂志》2023年第7期405-412,共8页Adverse Drug Reactions Journal

基　　金：北京市科技计划课题(Z191100007619037);北京市医院管理局2018年度消化内科学科协同发展中心重点项目(XXT27)。

摘　　要：目的探讨慢性药物性肝损伤(DILI)的流行概况、临床特征、危险因素及预后。方法采用多中心、开放、回顾、非干预性的流行病学调查方法,根据入选标准纳入中国308家医院2012年1月1日至2014年12月31日住院治疗的DILI患者。收集患者的病历资料,将DILI患者分为慢性和急性2组,比较2组患者临床及实验室特征和预后,分析2组患者的可疑致病药物,采用logistic回归对慢性DILI发生的影响因素进行单因素和多因素分析。结果共25 927例患者纳入研究,其中急性DILI(急性组)22 556例(87.0%),慢性DILI(慢性组)3 371例(13.0%)。与急性组比较,慢性组患者女性更多见,年龄更高,有肝病史者更多,从服药至发现肝损伤的时间更长,消化系统症状(包括食欲不振、腹胀、恶心、呕吐等)、疲乏、黄疸、瘙痒、肝区疼痛/不适、出血倾向者更多,丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、总胆红素和国际标准化比值更高,而血清白蛋白和血小板计数更低,终末期肝病模型评分≥15分者占比更高,全因病死率和肝病相关死亡率更高,差异均有统计学意义(均P<0.05)。logistic回归多因素分析结果显示,男性[比值比(OR)=0.76,95%置信区间(CI):0.69~0.83]是慢性DILI的保护因素,而既往肝病史(OR=2.00,95%CI:1.82~2.19)和低白蛋白血症(OR=0.96,95%CI:0.95~0.96)是慢性DILI的独立危险因素。结论研究时段308家医院DILI住院患者中慢性DILI占比为13.0%。与急性DILI比较,慢性DILI患者年龄更高,女性患者更多,肝损伤更严重,预后较差;其中女性、有肝病史和低白蛋白血症是发生慢性DILI的独立危险因素。Objective To investigate the prevalence,clinical characteristics,risk factors,and prognosis of chronic drug⁃induced liver injury(DILI).Methods A multicenter,open,retrospective,non⁃interventional epidemiological survey was conducted.According to the inclusion criteria,patients with DILI and hospitalized in 308 hospitals in China from January 1,2012 to December 31,2014 were enrolled,and medical records of the patients were collected.The patients with DILI were divided into chronic and acute DILI groups.The clinical characteristics,laboratory tests,and prognosis in patients of the 2 groups were compared,and the suspected drugs that induced the liver injury were analyzed.Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results A total of 25927 patients were enrolled in the study,including 22556(87%)with acute DILI(acute DILI group)and 3371(13%)with chronic DILI(chronic DILI group).In the chronic DILI group,there were high proportion of women and the patients were older in age;more patients were with a history of liver disease and the time from medication to DILI was longer;more patients had digestive system symptoms(including loss of appetite,abdominal distension,nausea,vomiting,etc.),fatigue,jaundice,pruritus,liver pain/discomfort,bleeding tendency;the alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and international normalized ratio were higher,while the serum albumin and platelet counts were lower;the proportion of patients with model for end⁃stage liver disease score≥15 was higher;the all⁃cause mortality rate and liver disease⁃related mortality rate were higher,compared with the acute DILI group.The differences above-mentioned were statistically significant(all P<0.05).Multivariate logistic regression analy⁃sis showed that male was protective factor[odds ratio(OR)=0.76,95%confidence interval(CI):0.69-0.83],while previous liver disease history(OR=2.00,95%CI:1.82-2.19)and hypoalbuminemia(OR=0.

关 键 词：化学和药物性肝损伤 慢性 胆汁淤积 疾病特征 多中心研究 

分 类 号：R575[医药卫生—消化系统]