- Acetaminophen is the leading cause of liver injury reported to U.S. poison centers, with cases rising nearly 400% since 2000.
- More than 80% of patients with drug-induced liver damage required hospital care, according to a new UVA Health study.
- Alcohol was the second most common cause of liver injury, and combining it with acetaminophen compounds the danger.
- Single-ingredient acetaminophen exposures increased steadily even after FDA action reduced injuries from combination products.
- Experts warn the drug is in over 600 products and can cause severe liver damage in just 24 hours when exceeding 4,000 milligrams.
Calls to U.S. poison centers involving liver injuries from medications, alcohol and other foreign substances have skyrocketed nearly 400% since 2000, with acetaminophen—the active ingredient in Tylenol and hundreds of other products—emerging as the top culprit, according to a new UVA Health study published in Clinical Gastroenterology and Hepatology.
Researchers led by Dr. Christopher P. Holstege, director of UVA Health's Blue Ridge Poison Center, analyzed 24 years of national poison data and identified 220,160 cases of xenobiotic-induced liver injury. This is damage caused by substances not naturally found in the body. The population-adjusted rate jumped from 10.9 cases per million people in 2000 to 52.9 per million by 2024. More than 80% of injured patients required hospital care.
"Xenobiotic-induced liver injuries reported to U.S. poison centers have steadily increased," Holstege said. "The public should be aware of potential liver injury with various substances that are readily available to consumers."
Acetaminophen leads the list despite past regulatory action
Acetaminophen was the most frequently implicated substance, a finding consistent with prior research identifying it as the leading cause of acute liver failure in the United States. The study found that after the FDA capped the amount of acetaminophen allowed in combination prescription products, related injuries dropped by 60% to 85%. However, exposures from single-ingredient acetaminophen—the type found in over-the-counter pain relievers—climbed steadily across the entire study period.
Women had higher rates of acetaminophen-related liver injury than men, and the study found suspected suicide was the leading reason for exposure in both sexes.
"Liver injuries reported to poison centers have increased substantially over the past 25 years, with acetaminophen emerging as a growing contributor," Holstege said. "Our study findings highlight the important role poison centers play in toxico-surveillance."
Dr. Ke-Qin Hu, a liver disease specialist at UCI Health, notes that severe damage can occur in just 24 hours if individuals exceed four grams—or 4,000 milligrams—of acetaminophen. That threshold is surprisingly easy to cross, particularly during cold and flu season when people often combine multiple medications containing the drug.
Alcohol and everyday combinations compound the risk
Alcohol was the second-most common cause of liver injuries in the study, showing up more often in men than women, although cases in both sexes climbed during the COVID-19 pandemic and have kept rising since. The combination of acetaminophen and alcohol poses particular danger, with even two grams of the drug capable of causing problems when mixed with alcohol.
Researchers also found more liver injuries tied to stimulants, street drugs, herbal supplements and environmental toxins, but none came close to acetaminophen or alcohol in frequency.
The findings carry particular weight given acetaminophen's ubiquity. Present in more than 600 prescription and over-the-counter products—Vicodin, Percocet, Midol, Sudafed and Nyquil among them—the drug is the most common medication ingredient in the United States. Each year, approximately 1,600 cases of acute liver failure and 500 deaths are attributed to acetaminophen overuse.
Patients deserve clearer warnings, not just caution
Experts urge patients to read Drug Facts labels carefully, avoid taking multiple products containing acetaminophen simultaneously, and avoid alcohol when using the drug. Those who suspect an overdose should call Poison Control at 1-800-222-1222 immediately.
The rising toll raises a fair question: why isn't a drug found in 600-plus household products carrying louder, harder-to-miss warnings? Acetaminophen is cheap, widely available and profitable precisely because it's sold with minimal friction. But minimal friction also means minimal disclosure. Consumers managing pain or fever deserve straightforward information about dosing limits and interactions, not fine print buried on the back of a box, so they can make informed decisions instead of finding out about the risks after the damage is done.
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