A consortium comprising researchers from Newcastle, Liverpool, Nottingham, and London have recently been funded by the Department of Health to study the genetics of drug-induced liver injury relating to

• Co-amoxiclav and flucloxacillin
• Anti-TB drugs.

The study called DILIGEN is described in more detail on the project website. The project, led from Newcastle by Prof Ann Daly, involves collecting DNA from cases and suitable controls for a detailed candidate gene study with the aim of identifying polymorphisms predictive of the development of liver injury related to antimicrobials. We are depending on physicians who may have seen patients developing liver injury with any of these drugs to put us in contact with suitable cases, as well as controls who have not suffered liver injury.

Inclusion criteria for cases are either: (a) clinically apparent jaundice or bilirubin > 40 µmol/l (after exclusion of cases due to haemolysis), or (b) ALT >5x upper limit of normal (ULN) or (c) ALP >2x ULN plus any raised bilirubin above ULN. If any patients under your care either in the past or currently have suffered DILI related to the main anti-TB drugs (isoniazid, rifampicin, pyrazinamide, ethambutol), to flucloxacillin or to coamoxiclav please contact our study research nurse who is co-ordinating recruitment, Jill Henderson. Jill will email some text which you may print out on your headed notepaper to send to the potential study candidates and she will post you a patient information sheet which includes a form to indicate interest in the study, together with a sample consent form and two prepaid envelopes. If the patient returns the form to us, indicating interest in taking part in the study, one of our four country-wide study nurses will arrange a visit to the patient at home or in the out-patient department, to collect the relevant clinical information and a blood sample for DNA and serum preparation. At this stage, we would ask you to nominate at least one additional patient who has received the drug treatment but not suffered liver injury and to send a letter and study details to this person as well, so that they can be recruited as a control. The nurse will also visit your hospital to collect relevant information from the case-notes. If the patient is an inpatient, we will send you an information sheet and consent form for you, or one of your team, to consent the patient. If they agree to take part, one of the study nurses will visit them in hospital to collect clinical details and blood samples.

The study has full MREC approval on a "no local investigator" basis. We are currently in the process of registering the project with relevant hospital R&D departments. This means there would be no added work burden on you or your department beyond sending Jill Henderson an e-mail when you see a potential case, sending out the initial letter and study details to the patient and then nominating a control. We believe this study will provide valuable information capable of improving patient care and hope you will be willing to participate.

If you would like any additional information on the study, please contact Ann Daly or Chris Day

Prof Ann Daly
Diligen Project Leader