Old problem, new solutions: biomarker discovery for acetaminophen liver toxicity

Expert Opin Drug Metab Toxicol. 2019 Aug;15(8):659-669. doi: 10.1080/17425255.2019.1642323. Epub 2019 Jul 15.

Abstract

Introduction: Although the hepatotoxicity of acetaminophen is a well-known problem, the search for reliable biomarker of toxicity is still a current issue as clinical tools are missing to assess patients intoxicated following chronic use, sequential ingestion, use of modified release formulations or in case of delayed arrival to hospital. The need for new specific and robust biomarkers for acetaminophen toxicity has prompted many studies exploring the use of blood levels of acetaminophen derivatives, mitochondrial damage markers, liver cell apoptosis and/or necrosis markers and circulating microRNAs. Areas covered: In this review, we present a concise overview of the most promising biomarkers currently under evaluation including descriptions of their properties with respect to exposure type, APAP specificity, and potential clinical application. In addition, we illustrate the power of new technologies for biomarker research and describe their current application to the field of acetaminophen-induced hepatotoxicity. Expert opinion: Recently the use of extracellular vesicles isolation in combination with omics techniques has opened a new perspective to the field of biomarker research. However, the potential of those new technologies for the prediction and monitoring of hepatic diseases and acetaminophen toxicity has not yet been fully taken into consideration.

Keywords: Biomarker discovery; acetaminophen; circulating microRNAs; extracellular vesicles; liver toxicity; metabolomics.

Publication types

  • Review

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Acetaminophen / pharmacokinetics
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects*
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Humans
  • MicroRNAs / metabolism
  • Mitochondria / pathology
  • Research Design

Substances

  • Analgesics, Non-Narcotic
  • Biomarkers
  • MicroRNAs
  • Acetaminophen