MicroRNA Levels Indicate Acetaminophen Poisoning In Blood Tests

When doctors in the emergency room suspect that a patient has overdosed on the popular painkiller acetaminophen, they want to verify the diagnosis quickly before liver damage sets in. But that’s not always possible.

Now researchers report a group of 11 biomarkers that, if validated in large groups of patients, might be a rapidly detectable signature of acetaminophen poisoning and a sensitive indicator that emergency treatment is working (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1412608111).

Some 78,000 Americans show up at hospitals because of acetaminophen overdoses each year. “Often the people who come in are in a state where they can’t report what’s happened to them,” explains Victor R. Ambros, who led the new work.

When administered soon after an overdose, N-acetyl­cysteine can mitigate liver damage. But the traditional biomarker, the enzyme alanine aminotransferase, can take 72 hours to peak in the bloodstream and is not specific to acetaminophen poisoning. So physicians approached Ambros, a biologist at the University of Massachusetts Medical School, and asked him to look into microRNAs as acetaminophen poisoning indicators.

MicroRNAs—short RNA strands that regulate gene expression—are promising biomarkers for many diseases, says James Dear, an expert on acetaminophen poisoning at Scotland’s University of Edinburgh who wasn’t involved with the work. Prior work showed that microRNAs can detect liver toxicity earlier than other biomarkers, he points out.

This turns out to be true for acetaminophen poisoning as well. Ambros’s team analyzed blood samples from 49 patients and found 11 microRNAs that spiked in concentration more rapidly than alanine aminotransferase during acetaminophen overdose. They also decreased more quickly in response to treatment. Ambros will study more patients to confirm the results.

The 11 microRNAs occur at attomolar levels in the bloodstream and during poisoning can increase anywhere from 10- to 100-fold. Ambros’s team used quantitative real-time polymerase chain reaction to detect those changes. Although finding the biomarkers is an achievement, “the technique itself is a little brute force” for emergency room blood work, says Robert M. Corn, who develops microRNA profiling tools at the University of California, Irvine. Ambros agrees, saying, “We’re working on adapting assays to more straightforward platforms.”