Patient Recruitment, Phenotyping and Disease Stratification

Workstrand 1 will develop a comprehensive PBC cohort and bioresource. This will contain fully anonymised medical information on patients with PBC including symptoms, laboratory data and response to current treatments (disease stratification). The bioresource will contain clinical samples such as blood and DNA that can be used to identify markers that predict drug response and disease progression. By developing a large cohort of PBC patients we will be able to identify patients who can be recruited to clinical trials (Workstrand 3) as well as supporting laboratory studies (Workstrand 2) to develop potential new treatments.

Workstrand 1 will therefore co-ordinate national patient recruitment with storage (biobanking) of serum, urine, stool and DNA to achieve a final cohort of over 4,000 patients. This group will also be grouped or stratified by their response to the commonest treatment for PBC, ursodeoxycholic acid (UDCA or “urso”). Workstrand 1 will also develop the project database and health informatics system to allow the development of better care pathways for PBC (Workstrand 3).

Included in Workstrand 1 will also be a ‘nested’ study of high-risk young and UDCA non-responding patients who will undergo more detailed study including liver biopsy to understand at the cellular level why some patients do not respond to treatment.

Workstrand 1 will be co-ordinated in the Academic Department of Medical Genetics, University of Cambridge in collaboration with Newcastle University and The Sanger Centre. These centres already have considerable experience in large scale genetic & clinical studies in PBC. The Workstrand 1 leaders in Cambridge are Dr Graeme Alexander (Consultant Hepatologist), Dr Richard Sandford (Consultant Clinical Geneticist) and Dr George Mells (Clinical Lecturer in Hepatology). Disease modelling and genetic analysis will be undertaken by Professor Heather Cordell (Newcastle University) and Dr Carl Anderson (Sanger Centre)

UK-PBC started in 2007 as a national effort to build a large patient cohort for genetic studies to understand whether genetic factors were important in the development of PBC. DNA samples from the cohort were used to identify variation in the human genome that were associated with PBC. These studies were undertaken as part of Wellcome Trust Case Control Consortium 3 and also supported by The Medical Research Council, The PBC Foundation, The Isaac Newton Trust and Addenbrooke’s Charitable Trust. Since 2008 the UK-PBC genetics project has been on the portfolio of the National Institute for Health Research (NIHR) Comprehensive Research Network (CRN) and is now a research network consisting of all NHS Trusts throughout the UK and forms an intergral part of UK-PBC.