Test spots acetaminophen-related liver toxicity

In patients with acute liver failure, a novel test can determine whether acetaminophen toxicity is involved, research suggests.

The test, which measures chemical byproducts of acetaminophen that are released into the blood, is "both sensitive and specific for acetaminophen toxicity, Dr. Timothy J. Davern II of the University of California at San Francisco told Reuters Health.

Davern anticipates that this test, which is based on widely available technology, will "aid in the clinical management of this important problem."

Acetaminophen (in painkillers such as Tylenol) is present in more than 600 separate products and is generally safe when used at up to the maximum daily doses recommended on package labeling.

However, more than 56,000 emergency room visits and nearly 500 deaths in the US each year are attributed to acetaminophen toxicity, owing to either intentional or unintentional overdoses. Acetaminophen toxicity is currently the most common cause of acute liver failure in the US and Europe.

Although intentional acetaminophen overdose is fairly easy to diagnose, in unintentional overdoses, the diagnosis can be elusive, leading to a delay in the administration of potentially life-saving treatment, Davern and colleagues point out in the journal Gastroenterology.

In animal models, "serum acetaminophen-protein adducts" or mutations, are specific biomarkers for drug-related toxicity, and Davern's team has found that the same is true in humans.

They examined serum samples collected from 66 patients with acute liver failure. Of these, 20 were from patients with well-characterized acetaminophen-related liver failure. Others were from patients with other well-defined causes or with liver failure of unknown origin.

Acetaminophen-protein adducts were detected in all 20 of the patients with acetaminophen-related liver failure. They were also seen in almost 7 of 36 indeterminate cases, suggesting that acetaminophen might have been involved.

"The cases of cryptogenic acute liver failure that previously had defied diagnosis were apparently caused by occult acetaminophen toxicity," Davern told Reuters Health. "These results suggest that the problem of acetaminophen toxicity is even greater than we had previously realized," he said.

SOURCE: Gastroenterology March 2006.