Measurement of serum acetaminophen-protein adducts in patients with acute liver failure

Gastroenterology. 2006 Mar;130(3):687-94. doi: 10.1053/j.gastro.2006.01.033.

Abstract

Background & aims: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients.

Methods: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury.

Results: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury.

Conclusions: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / metabolism
  • Acetaminophen / poisoning*
  • Acetylcysteine / therapeutic use
  • Adolescent
  • Blood Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Liver Failure, Acute / blood
  • Liver Failure, Acute / chemically induced*
  • Liver Failure, Acute / diagnosis
  • Male
  • Middle Aged
  • Poisoning / diagnosis

Substances

  • Blood Proteins
  • Acetaminophen
  • Acetylcysteine