Acetaminophen has emerged as the primary cause of a sharp increase in liver injuries across the United States over the last quarter century, according to researchers in Virginia. Data on calls to poison centers involving medications, alcohol, supplements, and other substances showed that reported liver injuries surged nearly 400 percent overall.
Acetaminophen, the active ingredient in Tylenol, was the most common substance linked to liver injury throughout the 2000 to 2024 study period. "Liver injuries reported to US poison centers have steadily increased," said Dr Christopher Holstege, the emergency medicine doctor behind the study. "The public should be aware of potential liver injury with various substances that are readily available to consumers."
Millions of doses of acetaminophen are purchased in the United States every year to treat muscle aches, colds, and the flu. The FDA states that the painkiller is safe and effective when taken at the right dose, which is no more than 1,000 milligrams every four to six hours for adults. However, higher doses can build up in liver cells and cause potentially irreversible organ damage.
Liver function and overdose symptoms
The liver is a vital organ responsible for filtering waste out of the blood and generating essential chemicals. Warning signs of an acetaminophen overdose include nausea, vomiting, abdominal pain, confusion, and jaundice, or a yellowing of the skin and the whites of the eyes. In severe cases, the damage may lead to needing a liver transplant or could result in death.
In the study, researchers analyzed data on 220,000 cases of xenobiotic liver injuries, which are injuries to the liver caused by substances not typically found in the body, reported to the poison control system from 2000 to 2024. Over the study period, the rate of liver injuries from all causes increased from 10.9 per million to 52.9 per million, more than quadrupling. Annually, there were 2,400 cases of liver injury from toxic substances reported in 2000, surging by 500 percent to 14,500 by 2021.
More than 80 percent of reported cases required hospitalization, and death was reported in about six percent of cases.
Common causes of toxic liver injury
Acetaminophen was the most common substance to cause injury, behind 45 percent of liver injuries reported among women and 33 percent of those among men. Injuries from the drug dropped in the 2010s after health officials reduced the number of products containing acetaminophen in combination with other drugs, such as acetaminophen with hydrocodone and acetaminophen with oxycodone, but continued to increase afterward.
Alcohol was reported to be a distant second cause, behind 19 percent of liver injuries reported among men and 13 percent of those recorded among women. Other less common causes of liver injuries included dietary and herbal supplements and environmental toxins.
Researchers said suspected suicide using acetaminophen was the most common reason for a liver injury in both males and females. In some cases, it was linked to accidental overdoses where people took acetaminophen and another drug without knowing it also contained acetaminophen.
Poison control and medication safety
"Liver injuries reported to poison centers have increased substantially over the past 25 years, with acetaminophen emerging as a growing contributor," Holstege added. "Our study findings highlight the important role poison centers play in toxico-surveillance."
"Medications should always be taken as directed by clinicians and according to pharmaceutical label instructions," he said. "Care must also be taken when consuming emerging substances that are unregulated. More studies are warranted to determine if specific populations are more at risk of liver injury."
The study is set to be published in the journal Clinical Gastroenterology and Hepatology.
