Calls to U.S. poison centers involving liver injuries linked to medications, supplements, alcohol and other foreign substances increased nearly fourfold between 2000 and 2024, according to a new study led by researchers at UVA Health. The analysis identified 220,160 reports of liver injury associated with xenobiotics, a scientific term for substances that originate outside the body and can disrupt normal biological processes. Xenobiotics include prescription and over-the-counter medicines, alcohol, dietary supplements, food additives, recreational drugs and environmental pollutants. The findings offer a 24-year view of how potentially toxic exposures are changing in the United States—and highlight the continuing danger posed by a familiar household medicine: acetaminophen.
Researchers led by Christopher P. Holstege, MD, director of UVA Health’s Blue Ridge Poison Center, examined reports submitted to U.S. poison centers from 2000 through 2024. When the data were adjusted for population growth, the rate of reported xenobiotic-related liver injury rose from 10.9 cases per million people to 52.9 cases per million. That represents an increase of almost 400 percent. The study does not mean that every liver injury in the country was captured, because poison center records reflect calls made by the public and health professionals rather than a complete national registry. However, poison centers are an important source of real-time toxicological surveillance, allowing scientists to detect changes in exposure patterns before they become visible in slower-moving health statistics.
More than 80 percent of the reported cases required inpatient medical care, suggesting that many of the exposures were clinically serious rather than minor or transient reactions. The liver is particularly vulnerable to toxic substances because it receives blood from the digestive tract and is responsible for chemically modifying, storing and eliminating a vast range of compounds. During this process, enzymes can convert an otherwise harmless substance into a reactive metabolite capable of damaging liver cells. Injury may begin with inflammation or cellular stress and progress to impaired bile flow, widespread hepatocyte death, acute liver failure and, in the most severe cases, the need for transplantation.
Medications accounted for the majority of the injuries recorded in the study, with acetaminophen emerging as the most frequently implicated substance. The drug is widely used to reduce pain and fever and is present in hundreds of prescription and nonprescription products. Under normal conditions, the liver safely processes most acetaminophen through chemical pathways that produce inactive compounds. A smaller fraction is converted into a reactive metabolite known as N-acetyl-p-benzoquinone imine, or NAPQI. The body normally neutralizes NAPQI with the antioxidant glutathione, but excessive doses can deplete glutathione and allow the metabolite to attack liver proteins and cellular structures.
The study found that liver injuries associated with acetaminophen-containing combination prescription products fell sharply—by approximately 60 to 85 percent—after the U.S. Food and Drug Administration limited the amount of acetaminophen permitted in those medicines. The decline suggests that regulatory action reduced the risk created by products that combined acetaminophen with other active ingredients, particularly when patients were unaware that multiple medicines contained the same pain reliever. At the same time, injuries linked to acetaminophen taken by itself increased steadily over the period studied. That pattern indicates that the drug remains a major source of toxic exposure even as one category of combination products has become safer.
Women had higher rates of acetaminophen-associated liver injury than men, while suspected suicide was the most common reason for exposure in both sexes. The data point to the importance of distinguishing accidental medication errors from intentional overdoses, because the medical response, prevention strategies and public health interventions differ substantially. Accidental exposure can occur when patients take several products with overlapping ingredients, misunderstand dosing instructions or use more than recommended while attempting to control severe pain or fever. Intentional ingestion requires rapid emergency assessment as well as mental health support. In either situation, early treatment is critical because symptoms may be mild or absent during the first stage of acetaminophen poisoning.
Alcohol was the second most common contributor to reported liver injuries, although it occurred far less frequently than acetaminophen-related cases. Alcohol-associated injuries were reported more often among men than women, but exposures increased in both groups during the COVID-19 pandemic. Alcohol can injure the liver through several overlapping mechanisms, including the accumulation of toxic metabolic products, oxidative stress, disruption of fat metabolism and activation of inflammatory pathways. Repeated heavy exposure can lead to fatty liver, alcoholic hepatitis and scarring, while a particularly large exposure or combination with other toxic substances may produce acute injury. The pandemic-era increase observed in poison center reports mirrors broader concerns about changes in alcohol consumption and substance use during periods of social disruption.
The researchers also documented rising reports involving stimulants, illicit drugs, herbal and dietary supplements and environmental toxins. These categories were less common than acetaminophen and alcohol, but they reflect a growing challenge for clinicians and poison specialists: the chemical landscape of consumer exposure is constantly changing. Supplements may contain concentrated botanical compounds, undisclosed pharmaceuticals or contaminants, and their formulations can vary between products and batches. Stimulants and street drugs may be mixed with other substances that increase toxicity, while environmental chemicals can affect the liver through metabolic activation or prolonged low-level exposure. Because many emerging products are not subject to the same premarket testing as approved medicines, identifying the exact substance and dose can be difficult during an emergency.
Holstege said the findings underscore the need for consumers to follow clinical advice and pharmaceutical label instructions, while exercising particular caution with unregulated or newly emerging substances. The results also demonstrate how poison centers can function as an early-warning system for public health. Their records can reveal shifts in drug-related harm, identify vulnerable populations and show whether a policy change is associated with a meaningful reduction in poisoning. Still, the study’s observational design cannot prove that every increase resulted from a single cause. Changes in calling behavior, awareness of poison center services, clinical recognition, product availability and patterns of intentional self-harm may all influence the numbers. Even with those limitations, the scale and persistence of the increase point to a widening need for medication safety education, clearer labeling, careful supplement oversight and rapid access to toxicology expertise.
UVA Health’s Blue Ridge Poison Center provides free, confidential guidance around the clock for suspected poison exposures, including medication overdoses and possible liver-toxic substances. The center can be reached in the United States at 1-800-222-1222. People should not wait for symptoms before seeking advice, particularly after a suspected acetaminophen overdose, because serious liver injury can develop while early warning signs remain subtle. The new study, published in Clinical Gastroenterology and Hepatology, was authored by Eleanor Blair Towers, Christopher P. Holstege, Scott Schmalzried and Rita Farah. The researchers reported that they had no financial interest in the work.
Subject of Research: People
Web References: https://makingofmedicine.virginia.edu/
References: Clinical Gastroenterology and Hepatology
Image Credits: UVA Health
Keywords: liver injury, acetaminophen, poisoning, xenobiotics, poison centers, medication safety, alcohol-related liver disease, dietary supplements, toxicology, UVA Health
