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

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
• liver toxicity
• circulating microRNAs
• metabolomics
• extracellular vesicles

Article highlights

• Acetaminophen is one of the world’s most widely used over-the-counter drug despite its hepatotoxic potential.

• There is a need for new biomarkers allowing early diagnosis and outcome prediction covering all acetaminophen intoxication scenarios.

• APAP-CYS immunoassay, APAP x ALT multiplication product and miR-122 are the most advanced APAP-induced hepatotoxicity biomarkers currently under evaluation.

• microRNA and metabolomic profiles are promising tools for the identification of sets of biomarkers allowing a broad diagnostic and prognostic range.

• Combination of omic technologies with circulating vesicle isolation opens new possibilities for the understanding of molecular mechanism of acetaminophen toxicity and biomarker identification.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.