Trends in the etiologies and outcomes of idiosyncratic drug-induced liver injury in the united states: The DILIN prospective registry, 2004 to 2024

BACKGROUND AIMS: Idiosyncratic drug-induced liver injury (DILI) is an infrequent cause of liver disease. The aim of this study is to report on temporal changes in the etiology and outcomes of idiosyncratic DILI in the United States DILIN Prospective study. METHODS: The presenting clinical features and outcomes of consecutive high causality DILI cases followed for 6 months at multiple DILIN sites from 2004 to 2024 were compared over time and by suspect drug class, age, sex, and prior chronic liver disease (CLD) status. RESULTS: Amongst the 1983 high causality cases, median age was 52 years, 59% were female, 54% had hepatocellular injury and antibiotics (41%) were the leading drug class. The median peak total bilirubin, INR and severity scores decreased significantly over time, as did the proportion of cases attributed to antimicrobials, including isoniazid and nitrofurantoin, and to central nervous system agents. In contrast, the proportion of herbal and dietary supplement (HDS) and antineoplastic drug cases (including checkpoint inhibitors), increased significantly. Patients with CLD had higher mortality compared to non-CLD patients. Pediatric patients presented more frequently with hepatocellular injury but had a lower overall and liver related mortality compared to adults. Oncology DILI patients had a 6-month mortality rate of 30% with most deaths attributed to non-liver related causes. CONCLUSIONS: Over the past 20 years, a decreasing proportion of DILI cases are attributed to antibiotics while an increasing proportion are attributed to HDS products and antineoplastics. Oncology patients and those > 65 years old have significantly higher overall and liver-related mortality.