title: Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine Adducts.
abstract: BACKGROUND
  Acetaminophen-cysteine adducts (APAP-CYS) are a serum biomarker of acetaminophen exposure, formed when the oxidative metabolite of acetaminophen binds to cysteine residues of hepatic proteins. APAP-CYS adducts become elevated in cases of acute liver failure following acetaminophen overdose and have been proposed as a diagnostic tool to identify acetaminophen-induced acute liver failure when standard testing is inconclusive.
  
  
  METHODS
  A 26-year-old female with history of unexplained, severe hepatitis presented with a second episode of severe hepatitis including coagulopathy and transaminase levels >10,000 U/L. The patient reported ingesting "only a couple" of acetaminophen tablets several days prior to her presentation. An acetaminophen concentration of 14 mcg/mL at presentation aroused suspicion that acetaminophen might have caused the patient's liver failure, despite her adamant denial of overdose. APAP-CYS adduct levels measured from serum obtained 4 days after her presentation and in two consecutive serum samples are reported alongside previously reported APAP-CYS levels.
  
  
  CONCLUSIONS
  The patient's APAP-CYS adduct levels were consistent with those seen in acute liver injury due to acetaminophen toxicity, even up to 1 week following presentation, and allowed for confirmation of acetaminophen toxicity as the cause of the her hepatitis. Overall, this case demonstrates the real-time application of APAP-CYS adducts as a biomarker to diagnose acetaminophen toxicity in patients with indeterminate acute liver failure.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Frey
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wiegand
authors.forename: Jody L
authors.initials: JL
authors.lastname: Green
authors.forename: Kennon J
authors.initials: KJ
authors.lastname: Heard
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wilkins
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gorodetsky
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dart
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000032:analysis* / Q000506:poisoning*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000032:analysis* / Q000506:poisoning*; D015415:Biomarkers / Q000032:analysis; D002498:Centrifugation; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis; D003956:Dialysis; D062787:Drug Overdose / Q000175:diagnosis; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000175:diagnosis*; D008111:Liver Function Tests
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D000082:Acetaminophen; C069744:acetaminophen cysteine; D003545:Cysteine