Autoimmune Liver Disease
Genetic studies in PSC and PBC
Patients are currently being recruited into a large genome wide association studies (GWAS) for both PSC and PBC (Roger Chapman principal investigator for the PSC project). 1500 PSC patients and 3000 PBC patients have been recruited from the UK. The hope is that new genes associated with these diseases will give new insights into pathogenesis and provide biomarkers for diagnosis. We are also applying funding in a joint project with Cambridge for a British GWAS into Autoimmune Hepatitis.
PSC may be sub-classified into large and small duct PSC. By definition small duct PSC only affects the smallest bile ducts within the liver and is thought to be associated with a more benign clinical course, whereas large duct PSC affects the large bile ducts and may be associated with progressive liver disease and cholangiocarcinoma. Genetic studies specifically looking at small duct PBMC are also underway in collaboration with the Norwegian PSC Study Group.
Significant external grant income is supporting the genetic studies and we are also grateful to the British PSC support group that provides regular annual funding for research in our unit.
Clinical studies in PSC and PBC
Biliary imaging in ulcerative colitis
It is known that ulcerative colitis and the development of colonic cancer is associated with PSC. The diagnosis of PSC is usually made in patients with colitis only when abnormal liver function tests (LFT's) are noted. More recently we have evaluated the presence of PSC in patients with total colitis and normal LFT's using MRCP scanning (a radiological scan of the bile ducts). This has shown a high prevalence of PSC in patients with UC who have normal liver function tests. This study has been extended to perform MRCP in UC patients with colonic dysplasia and cancer. The effects of these observations on disease progression are currently under investigation. These studies were carried out in collaboration with Dr Helen Bungay, Consultant Radiologist, Oxford Radcliffe Trust and is funded by the Oxford Research trust.
The effects of Ursodeoxycholic acid (UDCA) in PSC
Over the last decade we have studied the efficacy of moderate dose ursodeoxycholic acid (UDCA) in the treatment of PSC in 1) preventing the development of liver and biliary disease and 2) preventing the development of colonic cancer. Whilst the benefits of moderate dose UDCA remain unclear, UDCA does appear to reduce the colonic cancer risk.
We are currently investigating whether the biochemical responses to UDCA predict long term prognosis of PSC. In addition we are completing the first study into the natural history of patients with PSC associated with Crohn's Colitis.
Quality of life in PSC
The natural history of pouch function in PSC pts who have undergone colectomy is currently being evaluated using standardised quality of life (QoL) assessments.
Novel therapies for PBC
Currently UDCA is the only available treatment for PBC. The unit is currently evaluating nuclear receptor agonist with and without UDCA for the treatment of PBC.
IgG4 systemic disease
A recent and expanding area of research for our group is IgG4 associated systemic disease. We are carrying out a number of clinical studies into this disorder including natural history, relationship to IBD and laboratory based studies into T and B cell function. Emma Culver (clinical fellow) is currently leading this work in association with Ellie Barnes and Roger Chapman.
Other Biliary diseases
The unit also has a research interest into studies into Sphincter of Oddi dysfunction (SOD) with regard to natural history, response to treatment, Quality of life (Q of L) assessments and prospective psychological studies.