Clinical Features and Risk Factors for Drug-Induced Liver Injury: A Retrospective Study From China

• Published in: Clinical therapeutics Vol. 46; no. 8; pp. 597 - 603
• Main Authors: Ma, Xiaojuan, Chen, Zhuo, An, Jingzhi, Zhang, Cuixin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024; Elsevier Limited
• Subjects: Adult; Aged; Alanine transaminase; Alkaline phosphatase; Antineoplastic drugs; Appetite loss; Aspartate aminotransferase; Atorvastatin; Bilirubin; Biochemistry; Cardiovascular system; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - etiology; China - epidemiology; Chinese medicine; Clinical features; COVID-19; COVID-19 - complications; COVID-19 - epidemiology; Cyclophosphamide; Drug abuse; Drug-induced liver injury; Female; Gender; Hepatitis; Hospitals; Humans; Industrialized nations; Injure type; Life span; Liver; Liver diseases; Male; Malignancy; Medical records; Middle Aged; Patients; Pharmacovigilance; Prescription drugs; Product safety; Prognosis; Regression analysis; Retrospective Studies; Risk Factors; RUCAM; Statistical analysis; Traditional Chinese medicine; Young Adult; γ-Glutamyltransferase; China; Injure type; Clinical features; Drug-induced liver injury; Risk factors; RUCAM
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2024.04.014

•For the first time, risk factors for DILI patients who meet the diagnostic threshold versus DILI patients with only liver biochemical abnormalities who do not meet the diagnostic threshold are presented.•91 new hepatic injury risk signals were identified in this study, which are clinically alarming.•Compared the suspected drug information of Livertox and HepaTox, respectively, which objectively and accurately evaluated the signals of DILI. 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. 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. 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. 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.