MICA: Point-of-care assessment of drug-induced liver injury (POC-DILI)

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Taking an overdose of paracetamol is very common. There are around 100,000 cases of overdose that attend Emergency Departments in the UK every year. Of these, around half need emergency treatment with an antidote to prevent liver damage. The number of patients needing treatment in the UK is similar to the number of people who break their hips, another very common medical emergency. Paracetamol is directly responsible for the deaths of 100-150 people per year in the UK, predominately young people with no significant co-morbidity. The antidote to paracetamol is called acetylcysteine. There are problems with its use: (i) it is only fully effective when administered within around 8 h of taking the overdose. It is ineffective if treatment is delayed more than about 20 h. Therefore, treatment must be started as quickly as possible in those patients at risk of liver damage (ii) Adverse drug reactions (ADRs): nausea/vomiting occurs in more than half of recipients and allergic reactions in about a third. (iii) Prolonged duration: The regime is time consuming, taking at least 21 h to complete, leading to significant hospital bed occupancy. The blood tests used by doctors to identify which patients need treatment with acetylcysteine are currently not optimal. In this project we will develop a new test that will rapidly identify patients who need treatment following paracetamol overdose. The key advantages of our new test are:1. The marker of liver damage we will measure (cytokeratin-18, (K18)) is more sensitive than the current tests when the patient first arrives at hospital meaning doctors can pick up liver damage more quickly and start treatment promptly in those patients who need it. 2. Our assay is rapid (time to result 20 minutes)3. Our assay works with a finger prick of blood rather than needing blood from a vein.4. The assay is point of care which means the test is done in the Emergency Department rather than being sent to the hospital lab. This speeds up the process and eliminates the risk of blood samples being lost. 5. The assay is cheap, which means it can be used widely, including in low and middle income countries.In this project we will develop our K18 assay then perform a proof-of-concept clinical study in Emergency Departments to determine the accuracy of our unique solution to a common, but neglected, clinical problem.