A 25-year (2000–2024) retrospective analysis of the National Poison Data System evaluated trends in xenobiotic-induced liver injury (XILI) among adults ≥15 years in the U.S., stratified by sex, substance type, exposure intent, and medical outcome; secondary analyses focused on single-substance acetaminophen (APAP) and alcohol exposures.
220,160 XILI exposures were identified; population-adjusted rates rose nearly fourfold (10.9 → 52.9 per million). Over 80% required inpatient hospitalization. APAP-alone was the leading xenobiotic (males: 33%, females: 45%), with APAP-alone exposures surging 349% (males) and 380% (females), even as APAP-combination products fell 60–85% after early-2010s regulatory actions.
Retrospective surveillance data rely on voluntary poison center reporting, which may undercount cases not routed through poison centers. Biochemical thresholds (AST/ALT >100 U/L) used to define liver injury may not capture full clinical severity spectrum. Intent and substance attribution are self- or reporter-classified, introducing possible misclassification.
Clinicians should recognize APAP-alone as the dominant and rising driver of drug-induced liver injury, even as combination APAP products have declined — reinforce counseling on total daily APAP dose across all products. Poison center surveillance is a practical, real-time resource for tracking hepatotoxic trends and guiding prevention.
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