Mechanistic Biomarkers Provide Early and Sensitive Detection of Acetaminophen-Induced Acute Liver Injury at First Presentation to Hospital

• DOI: 10.1002/hep.26294
• Publication Date: 2013-02-07T00:26:50Z
• Authors: Daniel J. Antoine; James W. Dear; Philip Starkey Lewis; Vivien Platt; Judy Coyle; Moyra Masson; Ruben H. Thanacoody; Alasdair J. Gray; David J. Webb; Jonathan G. Moggs; Nicholas D. Bateman; Christopher E. Go...; Kevin B. Park
• Keywords: Acetaminophen; acetaminophen overdose; Aspartate transaminase

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated potential panel novel biomarkers (with enhanced liver expression or linked to mechanisms toxicity) identify patients with acetaminophen-induced acute injury (ALI) at first presentation when currently used markers are within normal range. In plasma sample from (n = 129), we measured microRNA-122 (miR-122; high specificity), mobility group box-1 (HMGB1; marker necrosis), full-length caspase-cleaved keratin-18 (K18; necrosis apoptosis), glutamate dehydrogenase (GLDH; mitochondrial dysfunction). Receiver operator characteristic curve analysis positive/negative predictive values were compare sensitivity report versus alanine transaminase (ALT) International Normalized Ratio (INR). all patients, significantly correlated peak ALT INR. presenting INR, miR-122, HMGB1, K18 identified development 15) not 84) degree accuracy outperformed ALT, acetaminophen concentration prediction subsequent ALI 11) compared no 52) 8 hours overdose.Elevations on hospital, soon after overdose, ALTs The application such biomarker could improve speed clinical decision-making, both design/execution