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Title: MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose.
Austin Authors: Wong, Anselm ;Nejad, C;Gantier, M;Choy, K W;Doery, James;Graudins, A 
Affiliation: Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Monash Toxicology Unit and Emergency Medicine Service, Monash Health, Victoria, Australia
Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia
Department of Medicine, Clinical Sciences at Monash Health, Monash University, Victoria, Australia
Monash Pathology Department, Monash Health, Victoria, Australia
Department of Emergency Medicine, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Jun-2019 2019-03-06
Publication information: Human & experimental toxicology 2019; 38(6): 646-654
Abstract: Paracetamol overdose is common and microRNA (miR)-122 expression is increased with liver injury. We aimed to measure miR-122 in the setting of an abbreviated paracetamol overdose treatment regimen. We compared miRNA expression in patients treated for paracetamol poisoning with an abbreviated 12-h intravenous acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) or a 20-h regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) (NACSTOP trial). miR-122 expression is increased (decreased cycle threshold (Ct) values) with paracetamol liver injury. We assessed miR-122 expression in patients receiving the two acetylcysteine regimens and in a separate group with acute liver injury (ALI). We examined 121 blood samples in 38 patients. After 20 h of acetylcysteine, median alanine transaminase (ALT) was 12 U/L (18, 14) versus 16 U/L (11, 21) ( p = 0.17) and median miR-122 Ct was 30.1 (interquartile range (IQR): 28.9, 33.3) versus 31.4 (28.9, 33.9) ( p = 0.7) in the NACSTOP abbreviated and control groups, respectively. Median normalized miR-122 Ct after 20 h of acetylcysteine was 2.2 (IQR 1.9, 6.4), 1.1 (0.7, 2.9), 63.9 (2.5, 168), 123.2 (40.9, 207.8) in the NACSTOP-abbreviated, NACSTOP-control, ALI and hepatotoxicity groups, respectively. There was no significant difference in ALT or miRNA between NACSTOP treatment groups and no signal of increased liver injury from an abbreviated 12-h acetylcysteine regimen. These findings suggest that an abbreviated acetylcysteine regimen in low-risk patients who have overdosed on paracetamol is safe. Further study is required to validate this finding utilizing miRNA as a comparative biomarker.
DOI: 10.1177/0960327119833740
ORCID: 0000-0002-6817-7289
PubMed URL: 30838890
Type: Journal Article
Subjects: Acetaminophen
Appears in Collections:Journal articles

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