Literature DB >> 25896948

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

Sean M Frey1, Timothy J Wiegand, Jody L Green, Kennon J Heard, Diana G Wilkins, Rachel M Gorodetsky, Richard C Dart.   

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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Year:  2015        PMID: 25896948      PMCID: PMC4469719          DOI: 10.1007/s13181-015-0476-x

Source DB:  PubMed          Journal:  J Med Toxicol        ISSN: 1556-9039


  10 in total

1.  Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure.

Authors:  Niraj Khandelwal; Laura P James; Corron Sanders; Anne M Larson; William M Lee
Journal:  Hepatology       Date:  2011-01-10       Impact factor: 17.425

2.  HepaRG cells: a human model to study mechanisms of acetaminophen hepatotoxicity.

Authors:  Mitchell R McGill; Hui-Min Yan; Anup Ramachandran; Gordon J Murray; Douglas E Rollins; Hartmut Jaeschke
Journal:  Hepatology       Date:  2011-02-11       Impact factor: 17.425

3.  Acetaminophen protein adduct formation following low-dose acetaminophen exposure: comparison of immediate-release vs extended-release formulations.

Authors:  Laura P James; Angela Chiew; Susan M Abdel-Rahman; Lynda Letzig; Andis Graudins; Peter Day; Dean Roberts
Journal:  Eur J Clin Pharmacol       Date:  2012-09-28       Impact factor: 2.953

4.  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.

Authors:  Sarah F Cook; Amber D King; Yan Chang; Gordon J Murray; Hye-Ryun K Norris; Richard C Dart; Jody L Green; Steven C Curry; Douglas E Rollins; Diana G Wilkins
Journal:  J Chromatogr B Analyt Technol Biomed Life Sci       Date:  2015-01-24       Impact factor: 3.205

Review 5.  Criteria for acetylcysteine treatment and clinical outcomes after paracetamol poisoning.

Authors:  W Stephen Waring
Journal:  Expert Rev Clin Pharmacol       Date:  2012-05       Impact factor: 5.045

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

Authors:  Timothy J Davern; Laura P James; Jack A Hinson; Julie Polson; Anne M Larson; Robert J Fontana; Ezmina Lalani; Santiago Munoz; A Obaid Shakil; William M Lee
Journal:  Gastroenterology       Date:  2006-03       Impact factor: 22.682

7.  Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose.

Authors:  L P James; E V Capparelli; P M Simpson; L Letzig; D Roberts; J A Hinson; G L Kearns; J L Blumer; J E Sullivan
Journal:  Clin Pharmacol Ther       Date:  2008-10-15       Impact factor: 6.875

Review 8.  Acetaminophen protein adducts: a review.

Authors:  G Randall Bond
Journal:  Clin Toxicol (Phila)       Date:  2009-01       Impact factor: 4.467

9.  Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure.

Authors:  Laura P James; Lynda Letzig; Pippa M Simpson; Edmund Capparelli; Dean W Roberts; Jack A Hinson; Timothy J Davern; William M Lee
Journal:  Drug Metab Dispos       Date:  2009-05-13       Impact factor: 3.922

10.  Acetaminophen-cysteine adducts during therapeutic dosing and following overdose.

Authors:  Kennon J Heard; Jody L Green; Laura P James; Bryan S Judge; Liza Zolot; Sean Rhyee; Richard C Dart
Journal:  BMC Gastroenterol       Date:  2011-03-14       Impact factor: 3.067

  10 in total
  1 in total

1.  2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside exacerbates acetaminophen-induced hepatotoxicity by inducing hepatic expression of CYP2E1, CYP3A4 and CYP1A2.

Authors:  Shangfu Xu; Jie Liu; Jingshan Shi; Zhengtao Wang; Lili Ji
Journal:  Sci Rep       Date:  2017-11-28       Impact factor: 4.379

  1 in total

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