Poison Center Xenobiotic Liver Injury Reports Rose 386% Since 2000, Driven by Acetaminophen Despite FDA Combination Caps

The study examined all xenobiotic exposures reported to U.S. poison centers over 24 years, defining liver injury by clinical or laboratory criteria. More than 80% of cases required hospitalization. Acetaminophen-containing products accounted for the largest share, followed distantly by alcohol; stimulants, herbal supplements, and environmental toxins contributed smaller fractions. Females showed higher acetaminophen rates, and intentional self-harm was the predominant exposure intent.

FDA-mandated limits on acetaminophen in prescription combination opioids reduced those exposures 60-85%, yet single-ingredient acetaminophen reports continued rising steadily. This pattern indicates substitution or incomplete risk communication rather than overall decline in use. Alcohol-related injuries increased during the COVID-19 period, especially among men, while unregulated supplements and street drugs remained minor but growing contributors.

These findings align with prior FDA surveillance and a 2018 Hepatology review documenting acetaminophen as the leading cause of acute liver failure in the United States. Observational poison-center data cannot establish incidence or causality and likely undercount mild cases. Next steps require linkage of poison-center records to electronic health data and targeted cohort studies to identify high-risk populations and test whether further single-agent labeling or packaging changes reduce harm.