title: Predicting risk in patients with acetaminophen overdose.
abstract: Acetaminophen (APAP) overdose is a very common cause of drug overdose and acute liver failure in the US and Europe. Mechanism-based biomarkers of APAP toxicity have the potential to improve the clinical management of patients with large-dose ingestions of APAP. The current approach to the management of APAP toxicity is limited by imprecise and time-constrained risk assessments and late-stage markers of liver injury. A recent study of 'low-risk' APAP overdose patients who all received treatment with N-acetylcysteine found that cell death biomarkers were more sensitive than alanine aminotransferase (ALT) and APAP concentrations in predicting the development of acute liver injury. The data suggest a potential role for new biomarkers to identify 'low-risk' patients following APAP overdose. However, a practical and ethical consideration that complicates predictive biomarker research in this area is the clinical need to deliver antidote treatment within 10 h of APAP overdose. The treatment effect and time-dependent nature of N-acetylcysteine treatment must be considered in future 'predictive' toxicology studies of APAP-induced liver injury.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
authors.forename: Prit
authors.initials: P
authors.lastname: Gill
authors.forename: Pippa
authors.initials: P
authors.lastname: Simpson
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006760:Hospitalization; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000097:blood*
chemical_list: D024243:HMGB1 Protein; D053538:Keratin-18; D035683:MicroRNAs; D000082:Acetaminophen