This study titled “Xenobiotic-Induced Liver Injury in the United States: A 25-Year Retrospective Analysis of National Poison Data System” looked at 25 years of U.S. poison-center data to see how often drugs, alcohol, chemicals, and other substances were associated with liver injury. The researchers analyzed reports from 2000 through 2024 involving people age 15 and older whose liver blood tests showed evidence of injury.
The main finding is concerning: reported exposures associated with liver injury increased nearly fourfold over the study period, from 10.9 to 52.9 cases per million people. In total, researchers identified more than 220,000 exposures associated with liver injury. These weren’t necessarily minor events—more than 80% resulted in hospitalization.
Acetaminophen stands out
Medications caused the large majority of these cases—85% among males and 94% among females. The most frequently implicated single substance was acetaminophen (APAP), the active ingredient in Tylenol and many other pain and fever medicines.
The researchers found an interesting shift. Liver-injury exposures involving combination medicines containing acetaminophen fell by roughly 60–85% after regulatory changes in the early 2010s. But exposures involving acetaminophen alone rose dramatically:
- 349% increase among males
- 380% increase among females
That suggests efforts to reduce acetaminophen in combination products appear to have helped, while single-ingredient acetaminophen has become an increasingly important source of serious liver injury.
Why this matters
Acetaminophen is widely available without a prescription and is generally safe when taken as directed, but excessive amounts can severely damage the liver. The findings are especially relevant as medicine increasingly relies on non-opioid pain relievers.
One important caveat: this is an analysis of cases reported to U.S. poison centers, not a study showing that nearly four times as many Americans overall are developing liver injury. Changes in reporting, medication use, and other factors could affect those numbers.
Bottom line: Drug- and chemical-associated liver injury reported to poison centers has risen substantially over the past 25 years, and acetaminophen—particularly single-ingredient acetaminophen—remains a major and growing contributor. The authors argue that poison-center data can help identify these trends earlier and guide prevention efforts.
