Related Experiment Video
Updated: Apr 14, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine
Sean M Frey1, Timothy J Wiegand, Jody L Green
1Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
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.
Related Concept Videos
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Drug Toxicity: Dose-Dependent Reactions
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

