Metabonome & Microbiome Variability & Differential Risk in PBC
Research type
Research Study
Full title
Metabonome & Microbiome Variability & Differential Risk in Primary Biliary Cirrhosis
IRAS ID
180419
Contact name
David EJ Jones
Contact email
Sponsor organisation
Newcastle upon Tyne Hospitals NHS Foundation Trust
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Primary Biliary Cirrhosis (PBC) is a rare, autoimmune liver disease which arises due to a combination of genetic and environmental factors. PBC is a highly gender-skewed disease, with approximately 90% of affected patients being female. In the UK, 7% of all adult elective liver transplants were performed for PBC in 2013/14. Risk is particularly high in younger patients. Although therapy exists in the form of Ursodeoxycholic acid (UDCA), its effectiveness is limited and it contributes least in the highest risk patients. At present, treatment in PBC is entirely focused on damage control rather than treating underpinning processes.
Three groups are at particularly increased risk of PBC and may represent an important setting in which to explore environmental triggers and ways to alter disease course. These groups are:
1) Individuals with the characteristic PBC antibody (anti-mitochondrial antibody, AMA) but who do not have liver injury (normal liver blood tests)
2) The daughters of mothers with PBC who have a 30-fold increased risk of PBC
3) Patients who have undergone liver transplantation for PBC and have a 1 in 3 chance of developing recurrent PBC within 5 years.PBC is characterised by changes in bile acids which lead to damage to liver cells and bile ducts. Bile acids are exposed to bacteria (bugs) in the gut (the microbiome). Bacteria in the gut are significantly different in females and males which is potentially important in a highly female-predominant disease such as PBC.
There will be four linked studies using state of the art technologies to explore differences in bile acids and gut bacteria between people with PBC, those ‘at risk’ of PBC, patients with primary sclerosing cholangitis (another liver disease) and healthy controls. If the theory is correct then we could potentially change the gut bacteria to reduce the risk of developing disease.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
15/EE/0455
Date of REC Opinion
18 Dec 2015
REC opinion
Further Information Favourable Opinion