The UK-PBC Nested Cohort Study (version 1)
Research type
Research Study
Full title
Stratified Medicine in Primary Biliary Cirrhosis (PBC): Understanding Disease Mechanisms and Targeting Therapies - The UK-PBC Nested Cohort Study
IRAS ID
137669
Contact name
David Jones
Contact email
Clinicaltrials.gov Identifier
MREC reference 07/H0606/96, Investigation of the genetic and molecular pathogenesis of primary biliary cirrhosis (The PBC Genetics Study)
Research summary
Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease that occurs in approximately 1/1000 women over the age of 40 in the UK. It is characterised by autoimmune destruction of the intrahepatic bile ducts. In patients with active disease, PBC may progress to cirrhosis and liver failure with attendant need for liver transplantation (LT).
The only medication licensed for treatment of PBC is ursodeoxycholic acid (UDCA). By convention, the therapeutic response to UDCA is defined in terms of the liver biochemistry (LFT) measured 12 months after starting treatment. It has been shown that survival in patients who respond to UDCA is comparable to that of the general population whereas LT-free survival in UDCA non-responders is substantially reduced. It has also been shown that earlier age-at-presentation is a risk factor for UDCA non-response and progressive liver disease.
The pharmaceutical industry has a major interest in finding novel medications for UDCA non-responders. However, the biological mechanisms of UDCA responsiveness are unknown, which impedes drug discovery and precludes an informed decision about which medications should be prioritised for clinical trials. In the UK-PBC Nested Cohort Study, we aim to elucidate the biological mechanisms of UDCA responsiveness. To do this, we will recruit known UDCA non-responders and matched UDCA responders from the UK-PBC Research Cohort, a cohort of approximately 4500 PBC patients that has been established for population-level studies of PBC. We will also recruit treatment-naive PBC patients who presented before the age of 50. All patients recruited to the UK-PBC Nested Cohort Study will undergo detailed cell- and tissue-based study with correlation to biological and clinical outcomes. By exploring the biological mechanisms of UDCA responsiveness, we hope to identify optimal therapeutic approaches. We aspire to targeted clinical intervention by the end of the funding period.
REC name
North West - Preston Research Ethics Committee
REC reference
14/NW/1146
Date of REC Opinion
31 Jul 2014
REC opinion
Favourable Opinion