Acetaminophen-Related Liver Failure

Acetaminophen poisoning has become the most common cause of acute liver failure in the United States. While attempted suicides still account for many cases, almost half are the result of unintentional overdose.

Acetaminophen is also the most widely used pain reliever in the United States--6% of Americans ingest it at least once a month--but taking more than the recommended dose can lead to fatal liver injury. While intentional overdoses generally present early after ingestion and can be treated with N-acetylcysteine, unintentional overdoses are usually not recognized until later.

As a result, University of Washington (Seattle, WA, USA) researchers suspected that patients with acute liver failure from unintentional acetaminophen overdoses would have more severe disease and worse outcomes than patients with intentional overdoses.

The researchers conducted a prospective study of patients presenting with acute liver disease to any of 22 academic centers participating in the acute liver failure study group, over a six-year period between 1998 and 2003. Of those diagnosed with acetaminophen-related acute liver failure, 44% had intentionally overdosed on the drug in suicide attempts and 48% had overdosed unintentionally.

Those who had unintentionally overdosed were older, used multiple acetaminophen-containing medications more frequently, and waited longer to seek care after their symptoms began. Most reported that they had been taking the medications specifically for pain. They were more likely to have severe hepatic encephalopathy than patients who had overdosed intentionally.

"Our data suggest that there is a narrow therapeutic margin and that consistent use of as little as 7.5 g/day may be hazardous,” the authors reported. Their data also suggest that there is no chronic form of acetaminophen injury, rather, a threshold of safety that, when breached, has devastating results.

The study was published in the December 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).




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