title: Measurement of serum acetaminophen-protein adducts in patients with acute liver failure.
abstract: OBJECTIVE
  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.
authors.affiliation: University of California at San Francisco, San Francisco, California, USA. timothy.davern@ucsf.edu [corrected]
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davern
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
authors.forename: Jack A
authors.initials: JA
authors.lastname: Hinson
authors.forename: Julie
authors.initials: J
authors.lastname: Polson
authors.forename: Anne M
authors.initials: AM
authors.lastname: Larson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Ezmina
authors.initials: E
authors.lastname: Lalani
authors.forename: Santiago
authors.initials: S
authors.lastname: Munoz
authors.forename: A Obaid
authors.initials: AO
authors.lastname: Shakil
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000293:Adolescent; D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000175:diagnosis
chemical_list: D001798:Blood Proteins; D000082:Acetaminophen; D000111:Acetylcysteine