Target biomarker profile for the clinical management of paracetamol overdose

Br J Clin Pharmacol. 2015 Sep;80(3):351-62. doi: 10.1111/bcp.12699. Epub 2015 Jul 29.

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.

Keywords: APAP-CYS; GLDH; HMGB1; biomarkers; hepatotoxicity; keratin-18; miR-122; miRNA; mtDNA; paracetamol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / pharmacokinetics
  • Acetaminophen / poisoning*
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Analgesics, Non-Narcotic / poisoning*
  • Animals
  • Biomarkers / blood*
  • Chemical and Drug Induced Liver Injury / blood*
  • Chemical and Drug Induced Liver Injury / etiology
  • Drug Overdose / blood
  • Drug Overdose / complications
  • Drug Overdose / therapy*
  • Glutamate Dehydrogenase / blood
  • HMGB1 Protein / blood
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Keratin-18 / blood
  • Membrane Glycoproteins / blood
  • MicroRNAs / blood
  • Models, Biological
  • Predictive Value of Tests
  • Receptors, Virus / blood
  • Risk Assessment

Substances

  • Analgesics, Non-Narcotic
  • Biomarkers
  • HAVCR1 protein, human
  • HMGB1 Protein
  • HMGB1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • KRT18 protein, human
  • Keratin-18
  • MIRN122 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs
  • Receptors, Virus
  • Acetaminophen
  • Glutamate Dehydrogenase