4.5 Review

Target biomarker profile for the clinical management of paracetamol overdose

Journal

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 80, Issue 3, Pages 351-362

Publisher

WILEY
DOI: 10.1111/bcp.12699

Keywords

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

Funding

  1. NC3Rs PhD Studentship [NC/K001485/1]
  2. NHS Research Scotland (NRS) Career Research Fellowship through NHS Lothian
  3. UK Regenerative Medicine Platform Niche Hub
  4. MRC [MR/L006758/1] Funding Source: UKRI
  5. Medical Research Council [MR/L006758/1] Funding Source: researchfish
  6. National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K001485/1] Funding Source: researchfish

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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.

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