基于文献的药物性肝损伤流行病学分析

An epidemiological analysis of drug-induced liver injury based on literature

目的:了解1998~2018年国内药物性肝损伤(DILI)的相关流行病学特征。方法:以"药物性肝损伤、药物性肝炎、药物性肝损害"为关键词,检索1998年1月至2018年12月中国知网、维普网、万方中文文献数据库我国DILI相关原始病例≥10例的文献。对DILI患者的性别、年龄、基础病史、用药种类、临床分型、临床表现和预后等相关数据进行总结分析。结果:纳入471篇相关文献,共计53 317例DILI患者,其中男26 641例(49.97%),女26 676例(50.03%),男女比为1∶1;366篇文献报道了平均年龄,其中327篇文献报道患者平均年龄>40岁。既往有饮酒史的患者291例,过敏史患者186例。排名前5位的致病药物分别为中药、抗结核药、抗微生物药、抗肿瘤药、解热镇痛药。292篇文献记录了35 163例DILI患者的临床分型,其中肝细胞损伤型21 061例(59.90%)、胆汁淤积型7 271例(20.68%)、混合型6 831例(19.42%)。共有117篇(25 095例)文献报道了临床表现,主要为乏力(10 377例)、黄疸(9 722例)、纳差(8 569例)、腹胀腹痛(3 919例)、恶心(3 717例)。共40篇(4 420例)文献记录了基础病史,包括感染性疾病、性病、肿瘤、消化系统疾病、皮肤、关节等17种疾病。385篇文献记录了41 362例患者的预后信息,其中治愈22 354例(54.04%)、好转15 827例(38.26%)、无效或出院2 415例(5.84%)、死亡766例(1.85%)。结论:药物性肝损伤患者男女比例相当,患者以中老年人居多;中药是引起我国DILI最主要的原因,抗结核药和抗微生物药紧随其后;损伤类型以肝细胞损伤型居多;临床表现以消化系统症状多见,部分患者无任何临床表现,仅有肝功能异常;基础病史以感染性疾病和肿瘤疾病多见;治愈及好转率92.31%,患者大多预后良好。及时发现并停用可疑药物,给予保肝抗炎等综合治疗是DILI的主要治疗方式。

Objective:To know the epidemiology features of drug-induced liver injury from 1998 to 2018 in China. Methods:Using drug-induced liver injury as key word, cases-analyse literatures on drug-induced liver injury from 1998 to 2018 in Chinese Periodical Full-text Datebase were searched,recorded gender, age, basic disease, types of drugs, clinical classifications, clinical characters and prognosis date, then analysed and made a conclusion. Results:A total of 471 articles were included, including 53317 patients with drug-induced liver injury, there were 26641(49.97%) male and 26676(50.03%) female, and the ratio of men to women was 1∶1. The mean age was reported in 366 literatures, among which 327 literatures reported that the mean age of patients was over 40 years old. There were 291 patients with previous drinking history and 186 patients with allergy history. The top five disease-causing drugs were traditional Chinese medicine, anti-tuberculosis drugs, anti-microbial drug, anti-tumor drugs and antipyretic and analgesic drugs. The clinical classification of 35163 drug-induced liver injury patients was recorded in 292 references, among which 21061 patients(59.90%) were hepatocellular injury, 7271 patients(20.68%) were cholestasis, and 6831 patients(19.42%)were mixed type. A total of 117 articles(25095 cases) reported clinical manifestations, including fatigue(10377 cases), jaundice(9722 cases), poor appetite(8569 cases), abdominal distension and pain(3919 cases), and nausea(3717 cases). Basic disease was recorded in 40 articles(4420 cases), including 1015 cases of infectious diseases(22.96%), followed by 321(7.26%) cases of tumor diseases, 318(7.19%) cases of digestive system diseases and 299(6.76%) cases of skin diseases. As for the prognosis,As for the prognosis,22324(54.01%) cases cured, 15827(38.29%) cases improved well, 2415(5.84%)cases invalid or discharged.766(1.85%) cases worse to dead. Conclusion:The proportion of men and women with drug-induced liver injury was similar. The majority of patients were middle-aged and elder. Traditional Chinese medicine is the most important cause of DILI in China. Most patients were hepatocellular. The clinical manifestations are mostly digestive system symptoms, some patients have no clinical manifestations, only abnormal liver function. The basic disease was mostly infectious disease and tumor disease and in general the prognosis is good. Detecting and stopping suspicious drugs in time and giving comprehensive treatment such as liver protection and anti-inflammation is the main treatment method.