Incidence of Drug-Induced Liver Injury in the Urban Primary Care Setting

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury is a growing clinical concern, but its burden in primary care remains poorly defined. In this setting, polypharmacy is common, and mild cases may go unrecognized. We aimed to determine the incidence, clinical characteristics, and outcomes of drug-induced liver injury in a large primary care population and to evaluate the diagnostic accuracy of laboratory alert criteria. METHODS: We conducted a prospective population-based study across 3 primary care centers in Barcelona (adult population, 91,798) from August 2022 to July 2024. An automated laboratory alert system triggered an alert for patients meeting predefined biochemical thresholds (alanine aminotransferase ≥5 × upper limit of normal, alkaline phosphatase ≥2 × upper limit of normal, or alanine aminotransferase ≥3 × upper limit of normal with bilirubin >2 × upper limit of normal). Expert hepatologists reviewed all identified cases to establish the most likely etiology. RESULTS: Among 38,112 patients undergoing laboratory tests, 153 met alert criteria, and 20 were diagnosed with drug-induced liver injury, yielding an annual incidence of 10.9 cases per 100,000 inhabitants (95% confidence interval, 6.7-16.8). All cases were mild, predominantly hepatocellular (70%), and resolved after drug withdrawal. Alanine aminotransferase ≥5 × upper limit of normal demonstrated the highest positive predictive value (25%) for drug-induced liver injury. Analgesics (40%), statins (20%), and dietary/herbal supplements (20%) were the most frequent causative agents. Relative incidence per 10,000 prescriptions was highest for metamizole (4.5) and diclofenac (3.5). CONCLUSIONS: Drug-induced liver injury represents a relevant cause of liver enzyme abnormalities in the primary care setting and is typically associated with favorable outcomes. Alanine aminotransferase ≥5 × upper limit of normal is the most reliable alert criterion, and analgesics, statins, and supplements are the leading culprits. Laboratory-linked alert systems may enhance early drug-induced liver injury detection in community practice.