Acetaminophen molecule: Past a certain point, acetaminophen overwhelms the liver’s ability to safely metabolize it and becomes a poison, killing liver cells.

Twenty years ago, the federal government funded the study of a condition quietly killing hundreds of Americans a year – acute liver failure, or ALF. Growing evidence had linked ALF to overdoses of acetaminophen, the popular over-the-counter pain medication many viewed as harmless at the time.

The Acute Liver Failure Study Group’s research led to an understanding of how acetaminophen poisoning became the leading cause of ALF in the United States. It’s now responsible for 46 percent of all cases and for approximately 500 deaths and 50,000 emergency room visits each year, said Dr. William M. Lee, Professor of Internal Medicine at UT Southwestern, founder of the study group, and an internationally renowned expert in liver disease.

“Taken in limited doses, acetaminophen is very safe,” explained Dr. Lee, who holds the Meredith Mosle Chair in Liver Disease in his honor. “But past a certain point, acetaminophen overwhelms the liver’s ability to safely metabolize it and becomes a poison, killing liver cells.”

In 2002 and 2009, Dr. Lee testified before FDA Advisory Committees examining whether the maximum daily dose of acetaminophen should be lowered and whether acetaminophen should be removed entirely from prescription opioid/acetaminophen combinations and over-the-counter mixtures. Those studies prompted the FDA in 2011 to ask pharmaceutical companies to reduce, within three years, the maximum dose for acetaminophen in prescription (opioid) drugs to 325 milligrams per tablet, down from the previously permitted 750 milligrams.

The FDA also directed drugmakers to add warnings about mixing acetaminophen with alcohol –which some studies have shown increases the risk of ALF – as well as clearer warnings about the possibility of liver damage.