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

  • Toxicology Observation
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Abstract

Introduction

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.

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References

  1. Bond GR. Acetaminophen protein adducts: a review. Clin Toxicol (Phila). 2009;47(1):2–7.

    Article  CAS  Google Scholar 

  2. James LP et al. Acetaminophen protein adduct formation following low-dose acetaminophen exposure: comparison of immediate-release vs extended-release formulations. Eur J Clin Pharmacol. 2013;69(4):851–7.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Heard KJ et al. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose. BMC Gastroenterol. 2011;11:20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. McGill MR et al. HepaRG cells: a human model to study mechanisms of acetaminophen hepatotoxicity. Hepatology. 2011;53(3):974–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Cook SF et al. Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: clinical and animal model applications. J Chromatogr B Anal Technol Biomed Life Sci. 2015;985:131–41.

    Article  CAS  Google Scholar 

  6. Khandelwal N et al. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology. 2011;53(2):567–76.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. James LP et al. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009;37(8):1779–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Davern 2nd TJ et al. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology. 2006;130(3):687–94.

    Article  CAS  PubMed  Google Scholar 

  9. Waring WS. Criteria for acetylcysteine treatment and clinical outcomes after paracetamol poisoning. Expert Rev Clin Pharmacol. 2012;5(3):311–8.

    Article  CAS  PubMed  Google Scholar 

  10. James LP et al. Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clin Pharmacol Ther. 2008;84(6):684–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Drs. Frey, Wiegand, and Gorodetsky have no conflicts of interest to disclose.

Drs. Green, Heard, and Dart received research funding from McNeil Consumer Healthcare via contracts with their institution. They did not receive personal compensation related to performance of any grant.

Dr. Wilkins is the primary investigator on an analytical service contract for acetaminophen-cysteine adducts analysis for McNeil Consumer Healthcare.

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Authors and Affiliations

  1. Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA

    Sean M. Frey

  2. Department of Emergency Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Timothy J. Wiegand & Rachel M. Gorodetsky

  3. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA

    Jody L. Green & Richard C. Dart

  4. Department of Emergency Medicine, University of Colorado School of Medicine, Denver, CO, USA

    Kennon J. Heard

  5. Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA

    Diana G. Wilkins

  6. Department of Pharmacy Practice, D’Youville College School of Pharmacy, Buffalo, NY, USA

    Rachel M. Gorodetsky

Authors
  1. Sean M. Frey
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  2. Timothy J. Wiegand
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  3. Jody L. Green
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  4. Kennon J. Heard
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  5. Diana G. Wilkins
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  6. Rachel M. Gorodetsky
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  7. Richard C. Dart
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Corresponding author

Correspondence to Rachel M. Gorodetsky.

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This manuscript is written in US English.

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Frey, S.M., Wiegand, T.J., Green, J.L. et al. Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine Adducts. J. Med. Toxicol. 11, 218–222 (2015). https://doi.org/10.1007/s13181-015-0476-x

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  • DOI: https://doi.org/10.1007/s13181-015-0476-x

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