University of Edinburgh

Medical Research Council (MRC)

DL_2023_004

Some medicines can cause the side effect of liver injury which is the commonest cause of liver failure (organ damage). Medicines causing liver injury are also a common cause of emergency hospital admissions and liver transplants; they are the main reasons medicines are removed from the market. Antibiotics are the main group of medicines which cause liver injury independent of the medicine dosage. In this project, we are investigating whether data routinely collected by the NHS can be used to monitor liver injury caused by two antibiotics. Both amoxicillin and co-amoxiclav (antibiotics) are commonly prescribed for chest problems but the latter antibiotic causes liver injury far more frequently than the former. This means we can compare the blood test results (identifying liver injury) for these two drugs. This is beneficial because data already being collected (blood test results) can be used to measure the safety of certain drugs.

Drug-induced liver injury (DILI) is the commonest cause of acute liver failure (60%) in the western world, with an estimated annual incidence of 13.9-24.0 per 100,000 globally 1-3. It is a common cause of emergency admissions 4 and liver transplantation 5, and is the leading cause of drug withdrawal from the market (18%) 3 6. Globally, idiosyncratic DILI is underreported and challenging to clinically identify, thus poses a significant risk to patient health and healthcare costs 7. Antimicrobials are the leading cause of idiosyncratic DILI (27%) worldwide, with co-amoxiclav (amoxicillin/clavulanic acid) and combination anti-tuberculosis (TB) being some principle causes 6. Upon the display of symptoms, the susceptive causative agent/agents are often withdrawn and the patient’s recovery is monitored before they are possibly re-challenged. This is particularly problematic for antimicrobial agents as the stopping and restarting of this class of drugs contributes to antimicrobial resistance 8. Therefore, we are investigating whether routinely collected data can be used to detect a signal for DILI following the administration of two commonly prescribed antibiotics- co-amoxiclav (associated with DILI, positive control) and amoxicillin (not associated with DILI, negative control). This will hold great value when new drugs are launched, as data such as these may be used for phase four or the post marketing monitoring of DILI occurrence. The NHS would directly benefit because as soon as drugs come onto the market, DILI can be detected using data that has already been collected (routinely collected data); subsequent incidences of DILI therefore may be prevented due to this method of pharmacovigilance.

Public Health Research

29/09/2023

De-Personalised

TRE