Acetaminophen Tops Poison Center Liver Injury Reports

Key Takeaways

• Across U.S. poison-center surveillance, reported xenobiotic-associated liver injury increased over time, and most cases required inpatient care.
• Acetaminophen was the most frequently implicated substance in reported U.S. poison-center liver injury cases.
• Reports involving acetaminophen-containing combination prescription products declined after FDA dose caps, while acetaminophen-alone exposures increased over time.
• Females had higher acetaminophen-associated reporting rates than males, and suspected suicide was the most common reported reason for exposure in both sexes.
• Alcohol was a distant second reported cause, appeared more often in men, and rose in both sexes during the COVID-19 pandemic.

Liver injury from widely available substances remains a persistent clinical burden, with acetaminophen the most familiar example because it is common in both over-the-counter and prescription products. That burden extends beyond medications to a broader xenobiotic landscape that includes alcohol, supplements, and environmental exposures that can come to medical attention through poison centers. Investigators examined long-term U.S. poison-center surveillance to clarify how these reported hepatotoxic exposures have changed over time.

In Eleanor Blair Towers and colleagues’ Clinical Gastroenterology and Hepatology analysis, Xenobiotic-Induced Liver Injury in the United States, investigators performed a 25-year retrospective review of the U.S. National Poison Data System (NPDS) covering 2000 to 2024 and identified 220,160 xenobiotic-associated liver injury cases. The summary defined xenobiotics as foreign substances not naturally found in the body, including drugs, food additives, alcohol, and environmental pollutants, but did not provide additional detail on case identification or analysis.

Population-adjusted reports rose from 10.9 per million to 52.9 per million, which the summary characterized as nearly a 400% increase. More than 80% of reported cases required inpatient care, and medications accounted for most cases, underscoring the scale of poison-center-reported liver injury burden in the United States.

Reports involving acetaminophen-containing combination prescription products fell by 60%–85% after U.S. Food and Drug Administration (FDA) dose caps, whereas acetaminophen-alone exposures increased steadily over time. Females had higher acetaminophen-associated rates than males, suspected suicide was the most common reported reason for exposure in both sexes, and alcohol was a distant second cause that appeared more often in men and increased during the coronavirus disease 2019 (COVID-19) pandemic. Smaller increases were also noted for stimulants and street drugs, herbal and dietary supplements, and environmental toxins, which remained far less common than acetaminophen- and alcohol-associated reports.

These data reflect poison-center-reported exposures involving liver injury rather than adjudicated national incidence. The available summary does not provide the exact liver injury case definition, denominator construction details, severity grading, or clinical outcomes beyond inpatient care. The investigators interpreted the overall pattern as evidence that poison-center surveillance can track changes in reported hepatotoxic exposures over time.

Acetaminophen remained central within a broader rise in U.S. poison-center liver injury reports, and the decline in combination-product exposures after FDA caps contrasted with continued growth in acetaminophen-alone exposures. The investigators concluded that the analysis underscores poison centers’ role in toxico-surveillance.

Clinician Questions

What counted as a xenobiotic in this U.S. poison-center liver injury analysis?

The investigators described xenobiotics as foreign substances not naturally found in the human body, and they said the category included drugs, food additives, alcohol, and environmental pollutants.

Which substance categories besides acetaminophen and alcohol also showed increases in poison-center liver injury reports?

The investigators also identified increases involving stimulants and street drugs, herbal and dietary supplements, and environmental toxins, while noting that these categories were much less common than acetaminophen- and alcohol-associated liver injury reports.

What does the National Poison Data System analysis not establish about xenobiotic-associated liver injury in the United States?

The findings reflect poison-center-reported exposures involving liver injury rather than adjudicated national incidence, and the available summary does not provide the exact liver injury case definition, denominator construction details, severity grading, or clinical outcomes beyond inpatient care.