A national effort to understand acute liver failure – two decades and 3,000 study participants later
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A multicenter study on acute liver failure initiated by UT Southwestern 20 years ago and funded by the National Institutes of Health (NIH) has increased understanding of this sometimes-fatal condition, leading in turn to improved, lifesaving patient care.
The Acute Liver Failure Study Group, now active at 12 sites in the U.S. and Canada, including UT Southwestern, has recruited more than 3,000 participants to date.
Information gathered from those patients over the years has given physicians a clearer picture of what acute liver failure (ALF) looks like and how best to treat it. The study group’s principal investigator, Dr. William M. Lee, Professor of Internal Medicine at UT Southwestern and a world-renowned liver disease expert, began the research effort in 1997 with an NIH grant. Funding support has continued, and is committed through at least 2020.
“ALF is extremely rare, with only about 2,000 cases in the U.S. each year,” said Dr. Lee, who holds the Meredith Mosle Chair in Liver Disease in his honor. “Because of its rarity, many physicians aren’t that familiar with this rapidly progressive and fatal liver disease and may not recognize it quickly.”
The impetus for the study began in 1993, when Dr. Lee noticed that more than half of the patients treated at Dallas’ Parkland Memorial Hospital for acute liver failure had excess quantities of acetaminophen. His findings were reported in The New England Journal of Medicine (NEJM) that year. A follow-up study, published in NEJM four years later, found that almost a third of the Parkland ALF patients had accidently poisoned themselves, simply trying to relieve pain. And, Dr. Lee’s research found, those accidental overdose patients were more likely to die.
Thanks to the study group’s efforts, gains have been made in the diagnosis and treatment of all forms of acute liver failure. Currently, the study group is evaluating a test developed at the University of Arkansas that rapidly detects the toxic byproducts of acetaminophen poisoning to identify an overdose patient quickly. If the test proves to be effective, it could be available in two to three years, Dr. Lee said.
A new medication to treat all forms of ALF is also under study by the group. Working with the North Carolina biopharmaceutical company Ocera Therapeutics Inc., the group has tested the safety and tolerability of this potential drug to treat brain edema before symptoms progress. Brain edema, or swelling, is a complicating factor of hepatic encephalopathy – a decline in brain function that occurs as a result of liver disease. In this condition, the liver cannot adequately remove toxins from the blood, leading to potential brain damage.