Acetaminophen, or Tylenol, is commonly used in the United States to eliminate aches and pains and reduce fever with few side effects. However, the drug is the leading cause of acute liver failure in the United States, and if liver damage is severe enough, the only lifesaving treatment is a liver transplant.
A novel method developed at the National Institute for Mathematical and Biological Synthesis at UT helps determine which patients will benefit from transplantation.
The topic of the underreported dangers of overdosing on acetaminophen has received ample attention following recent in-depth investigation by the radio program “This American Life” and public-interest journalism organization ProPublica.
There is a chemical antidote to acetaminophen poisoning, but it is effective only if administered within eight hours of an overdose. If liver damage is severe enough and the antidote is not administered early enough, the only lifesaving treatment is liver transplantation.
However, determining which patients need a transplant and which will recover is a major challenge in treating patients with acetaminophen overdose.
Chris Remien, a postdoctoral researcher at NIMBioS, and his research partners have developed a novel method to determine which patients will benefit from liver transplant in these instances. Rather than relying on purely statistical methods, Remien’s method is based on a dynamic model of acetaminophen metabolism and cellular damage.
In addition to making predictions on the need for a transplant, the model also defines a limit to how much acetaminophen someone can take over time before it causes liver damage.
“There is a simple threshold in the model because of how the liver processes acetaminophen, so that there is either very little liver damage or rapid damage, which may explain why patients who chronically overuse acetaminophen can eventually develop rapid liver damage,” Remien said.
The model has shown promise in a set of fifty-three patients from the University of Utah, but it still needs to be validated in a larger multicenter study before it can be used by physicians.
“We are currently collecting more data and collaborating with other groups in order to validate our method,” Remien said.
Collaborating on the project are Norman Sussman, associate professor of surgery at Baylor College of Medicine, and Fred Adler, professor of mathematics and biology at the University of Utah.
For more information about Remien’s model, view a video of his seminar talk at bit.ly/186aQbr.
The National Institute for Mathematical and Biological Synthesis brings together researchers from around the world to collaborate across disciplinary boundaries to investigate solutions to basic and applied problems in the life sciences.
To learn more, visit nimbios.org.
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