POC-DILI trial opens to recruitment

Paracetamol overdose is the leading cause of acute liver failure in the Western World. Every year, in the UK, there are >100,000 people who attend hospital following a paracetamol overdose, with around half requiring emergency treatment with the antidote n-acetylcysteine (NAC). The sooner NAC is administered, being optimally effective within 8 hours of paracetamol overdose, the better the chance of preventing drug-induced liver injury (DILI). Alanine transaminase (ALT) is the current gold standard for establishing DILI in patients. However, ALT increases too slowly after paracetamol overdose for the diagnosis of liver injury to occur so that treatment with NAC can have maximal efficacy. Therefore, there is a need for a test that can rapidly identify which patients are likely to develop liver injury following a paracetamol overdose, to enable prompt treatment, and thus improve patient outcomes. Cytokeratin-18 (K18) is a new biomarker of liver injury and can be detected earlier than ALT and can accurately identify patients with DILI within 8 hours of paracetamol overdose. Researchers have developed a new test, a point-of-care (POC) lateral flow assay (LFA), designed to detect K18 and enable early diagnosis of DILI.

The POC-DILI trial, funded by the Medical Research Council (MRC), is being led by Professor James Dear, Professor of Clinical Pharmacology at the University of Edinburgh. Data will be collected on each patient and will include time of overdose and amount of paracetamol ingested. At various time points, blood will be taken via finger prick, added to the lateral flow assay cassette and a visual reading will be taken at between 10-30 minutes. The LFA device works by capturing K18 via a sandwich immunoassay utilizing gold nanoparticles. The assay results will then be quantified using a handheld Raman Reader. The ability to quickly tell whether patients are likely to develop liver DILI will hopefully lead to better patient outcomes.