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Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine Adducts.

AbstractINTRODUCTION:
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.
CASE REPORT:
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.
DISCUSSION:
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.
AuthorsSean M Frey, Timothy J Wiegand, Jody L Green, Kennon J Heard, Diana G Wilkins, Rachel M Gorodetsky, Richard C Dart
JournalJournal of medical toxicology : official journal of the American College of Medical Toxicology (J Med Toxicol) Vol. 11 Issue 2 Pg. 218-22 (Jun 2015) ISSN: 1937-6995 [Electronic] United States
PMID25896948 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Analgesics, Non-Narcotic
  • Biomarkers
  • Acetaminophen
  • acetaminophen cysteine
  • Cysteine
Topics
  • Acetaminophen (analogs & derivatives, analysis, poisoning)
  • Adult
  • Analgesics, Non-Narcotic (analysis, poisoning)
  • Biomarkers (analysis)
  • Centrifugation
  • Cysteine (analogs & derivatives, analysis)
  • Dialysis
  • Drug Overdose (diagnosis)
  • Female
  • Humans
  • Liver Failure, Acute (chemically induced, diagnosis)
  • Liver Function Tests

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