目的:随着人类寿命的延长和抗肿瘤药COVID-19的爆发,抗感染药物,和心血管系统药物已经广泛应用,导致药物性肝损伤(DILI)的发病率逐年上升。这项研究旨在调查信号,临床特征,以及肝损伤患者的危险因素。
方法:对中国大陆某三甲医院2019-2021年临床诊断为DILI的住院患者进行回顾性分析。肝脏生化指标,统计患者的临床表现和可疑药物。我们通过RousselUclaf因果关系评估方法对生物化学符合国际严重不良事件协会推荐的诊断标准的患者进行因果关系评估,并将其与诊断为DILI但肝脏生化异常的同期患者进行比较,以确定损伤类型和DILI的危险因素。
结果:纳入了2639名DILI初始参与者中的1167名患者。根据受伤的靶细胞,可分为肝细胞损伤型351例(30.08%),胆汁淤积型损伤97例(8.31%),混合性损伤型27例(2.31%),生化异常型仅692例(59.30%)。涉及1738宗可疑毒品个案,349种药物,前3名的药物类别是抗肿瘤药物,抗感染药,和中药,用环磷酰胺,阿托伐他汀,和Liuzasulfapyridine排名前3位。患者的主要症状是尿液较深,食欲下降,和黄色巩膜。DILI患者的总体预后良好,有280例康复病例(23.99%),改善691例(59.21%),189例未好转(16.20%),死亡7人(0.60%)。性别差异显著,年龄,恶性肿瘤,丙氨酸氨基转移酶,天冬氨酸转氨酶,碱性磷酸酶,总胆红素,γ-谷氨酰转移酶,白蛋白,国际标准化比率,不同损伤类型患者的预后差异有统计学意义(P<0.05)。多因素Logistic回归分析显示女性(比值比[OR]=1.897,P<0.001),饮酒(OR=1.905,P=0.001),恶性肿瘤(OR=0.417,P<0.001),妊娠(OR=0.201,P=0.011)是影响DILI的独立因素。
结论:对于大多数肝损伤患者,表现为肝脏生化轻度升高,无其他症状(仅生化异常型)。其余患者主要是肝细胞损伤类型。女性和酗酒患者是DILI的危险因素,提醒临床医生加强安全用药教育,给予个体化治疗,定期监测患者肝功能指标。
OBJECTIVE: With the prolongation of human life expectancy and the outbreak of COVID-19, antineoplastic agents, anti-infective drugs, and cardiovascular system drugs have been widely applied, resulting in a growing incidence of drug-induced liver injury (DILI) year by year. This
study aimed to investigate signals, clinical characteristics, and risk factors in patients with liver injury.
METHODS: A retrospective analysis was conducted on inpatients clinically diagnosed with DILI from 2019 to 2021 in one tertiary hospital in mainland China. The hepatic biochemical indices, clinical manifestations and suspected drugs of the patients were counted. We determined causality assessed by the Roussel Uclaf Causality Assessment Method in patients that the biochemistry met the diagnostic criteria recommended by the International Serious Adverse Events Consortium and compared them with contemporaneous patients diagnosed as DILI but with hepatic biochemical abnormalities only to identify the injure types and risk factors for DILI.
RESULTS: A total of 1167 patients from 2639 initial participants with DILI were included. According to the injured target cells, it can be divided into hepatocellular injury type 351 cases (30.08%), cholestatic injury type 97 cases (8.31%), mixed injury type 27 cases (2.31%), and biochemical abnormal only type 692 cases (59.30%). It involved 1738 cases of suspected drugs, 349 drugs, and the top 3 drug categories were antineoplastic agents, anti-infectives, and traditional Chinese medicines, with Cyclophosphamide, Atorvastatin, and Liuzasulfapyridine as the top 3 in order of ranking. The main symptoms of patients were darker urine, decreased appetite, and yellow sclera. The overall prognosis of patients with DILI was favorable, with 280 recovered cases (23.99%), 691 improved cases (59.21%), 189 not improved cases (16.20%), and 7 deaths (0.60%). There were significant differences in gender, age, malignancy, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyltransferase, albumin, international normalized ratio, and prognosis among patients with different injury types (P < 0.05). Multiple logistic regression analysis showed that female (odds ratio [OR] = 1.897, P < 0.001), alcohol use (OR = 1.905, P = 0.001), malignancy (OR = 0.417, P < 0.001), and pregnancy (OR = 0.201, P = 0.011) were independent factors influencing DILI.
CONCLUSIONS: For most patients with liver injury, the manifestations are mild elevation of liver biochemistry without other symptoms (biochemical abnormal only type). The rest of the patients are predominantly of the hepatocellular injury type. Female and alcohol abuse patients are the risk factors of DILI, reminding clinicians to strengthen education on safe drug use, give individualized treatment, and regularly monitor liver function indexes in the patients.