title: Target biomarker profile for the clinical management of paracetamol overdose.
abstract: Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile.
authors.affiliation: Pharmacology, Toxicology & Therapeutics, University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh.
authors.forename: A D Bastiaan
authors.initials: AD
authors.lastname: Vliegenthart
authors.affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Antoine
authors.affiliation: Pharmacology, Toxicology & Therapeutics, University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh.
authors.forename: James W
authors.initials: JW
authors.lastname: Dear
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000506:poisoning*; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology; D062787:Drug Overdose / Q000097:blood / Q000150:complications / Q000628:therapy*; D005969:Glutamate Dehydrogenase / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood; D035683:MicroRNAs / Q000097:blood; D008954:Models, Biological; D011237:Predictive Value of Tests; D011991:Receptors, Virus / Q000097:blood; D018570:Risk Assessment
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; C491143:HAVCR1 protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C488421:KRT18 protein, human; D053538:Keratin-18; C531907:MIRN122 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D011991:Receptors, Virus; D000082:Acetaminophen; D005969:Glutamate Dehydrogenase
keywords: APAP-CYS; GLDH; HMGB1; biomarkers; hepatotoxicity; keratin-18; miR-122; miRNA; mtDNA; paracetamol