Predicting risk in patients with acetaminophen overdose

Abstract

Acetaminophen (APAP) overdose is a very common cause of drug overdose and acute liver failure in the US and Europe. Mechanism-based biomarkers of APAP toxicity have the potential to improve the clinical management of patients with large-dose ingestions of APAP. The current approach to the management of APAP toxicity is limited by imprecise and time-constrained risk assessments and late-stage markers of liver injury. A recent study of ‘low-risk’ APAP overdose patients who all received treatment with N-acetylcysteine found that cell death biomarkers were more sensitive than alanine aminotransferase (ALT) and APAP concentrations in predicting the development of acute liver injury. The data suggest a potential role for new biomarkers to identify ‘low-risk’ patients following APAP overdose. However, a practical and ethical consideration that complicates predictive biomarker research in this area is the clinical need to deliver antidote treatment within 10 h of APAP overdose. The treatment effect and time-dependent nature of N-acetylcysteine treatment must be considered in future ‘predictive’ toxicology studies of APAP-induced liver injury.

Keywords::

• acetaminophen
• acute liver injury
• biomarker
• HMGB1
• K18
• miR-122
• necrosis
• Rumack nomogram

Financial & competing interests disclosure

LP James is the principal investigator of two grants funded by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) to evaluate the measurement of acetaminophen protein adducts in patients with acetaminophen toxicity (RDK081406, R42DK079387). LP James is part-owner of Acetaminophen Toxicity Diagnostics, LLC, which received NIH grant support (R42DK079387). P Gill and P Simpson receive salary support from the two above grants. The authors have no other 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.

No writing assistance was utilized in the production of this manuscript.