US DILI Registry Shows Shifting Drug Causes and Outcomes, 2004–2024

Researchers compared clinical features and six-month outcomes among 1,983 high-causality cases of idiosyncratic drug-induced liver injury recorded at multiple US DILIN sites from 2004 to 2024. Median age was 52 years, 59% of patients were female, and 54% had hepatocellular injury. Antibiotics accounted for 41% of cases and were the leading drug class.

Over time, median peak bilirubin, INR and severity scores decreased. The proportion of cases attributed to antimicrobials—including isoniazid and nitrofurantoin—and central nervous system agents also fell. In contrast, the proportions attributed to herbal and dietary supplements and antineoplastic drugs, including checkpoint inhibitors, rose. Patients with chronic liver disease had higher mortality than those without it. Oncology patients had 30% six-month mortality, mostly from causes not related to liver injury; patients older than 65 years also had higher overall and liver-related mortality.

The findings describe changing patterns among cases captured by a prospective registry, rather than estimating population-level DILI incidence or risk from individual drugs. The reported trends may help inform clinical awareness, but the study does not establish why they occurred or support specific changes in treatment or monitoring.