2. Academic Validation
  3. Detection of Ophthalmic Acid in Serum from Acetaminophen-Induced Acute Liver Failure Patients Is More Frequent in Non-Survivors

Detection of Ophthalmic Acid in Serum from Acetaminophen-Induced Acute Liver Failure Patients Is More Frequent in Non-Survivors

  • PLoS One. 2015 Sep 25;10(9):e0139299. doi: 10.1371/journal.pone.0139299.
Gurnit Kaur 1,  Elaine M Leslie 2,  Holly Tillman 3,  William M Lee 4,  Diane P Swanlund 5,  Constantine J Karvellas 6,  US Acute Liver Failure Study Group
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Pathology, University of Alberta, Edmonton, Canada.
  • 2 Department of Laboratory Medicine, Pathology, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada.
  • 3 Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
  • 4 Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
  • 5 Department of Physiology, University of Alberta, Edmonton, Canada.
  • 6 Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, Canada.
PMID: 26407170 DOI: 10.1371/journal.pone.0139299
Abstract

Background/aim: Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAP-ALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with in-hospital survival in the absence of liver transplant.

Methods: Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004-2011).

Results: Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 μmol/l, p<0.05 for all). During the first 7 days of the study, survivors were less likely to require mechanical ventilation (55% vs. 88%), vasopressor support (9.8% vs. 67%) or renal replacement therapy (26% vs. 63%, p< 0.001 for all). Non-survivors were more likely to have detectable OA levels early (31% vs. 15%, p = 0.034) and late (27% vs. 11%, p = 0.02). However there were no significant differences in mean OA levels between non-survivors and survivors (early 0.48 vs. 0.36, late 0.43 vs. 0.37, P > 0.5 for all).

Conclusion: OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production.

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