A feasibility study in characterising real world linkage between primary to secondary care in South East England – a model to understand the natural history, management and clinical pathways in the care of the Primary Bukuary Cholangitis (PBC) patient.
|This study will evaluate the Safety and Efficacy of Obeticholic Acid (OCA) in subjects with Non alcoholic steatohepatitis (NASH)
NASH is a serious, chronic liver disease with a large unmet medical need and no approved treatments. The incidence of NASH is increasing and NASH is likely to be the leading cause of liver transplant by 2020.
Subjects for this study will be screened for a period of up to 12 weeks before entering the study. Approximately 2065 subjects (globally) with NASH will be randomised to receive OCA 10mg, OCA 25mg, or matching placebo in a 1:1:1 ratio for the duration of the study, in conjunction with local standard of care.
The cause of Primary Sclerosing Cholangitis (PSC) is unclear. However, there is evidence that genetic factors are important – we just don’t know which genes are involved. That’s what this project is about: we want to analyse DNA from people with PSC to identify which genes contribute to disease. In doing so, this study will contribute to a better understanding of what causes PSC and how it may be treated.
Methotrexate is an effective treatment for psoriasis as well as rheumatoid arthritis. But its use is limited by adverse effects, mainly the concern regarding liver scarring. Currently doctors rely upon performing liver biopsy to detect liver scarring. Although liver biopsy is the standard procedure used routinely to monitor liver scarring, it is preferable if we could develop a strategy to diagnose and monitor scarring in the liver using non-invasive tests.
We will enrol patients with psoriasis and rheumatoid arthritis who are on methotrexate treatment to participate in this study. All patients would complete a questionnaire and we will collect routine information such as
height, weight, waist, hip circumferences and blood pressure measurements. At the same consultation, alongside routine blood tests, a non-invasive test called fibroscan using an ultrasound like probe will be done. When combination of non-invasive raise the possibility of scarring patients will be assessed by liver specialists to decide whether liver biopsy is appropriate. This will allow us to evaluate the performance of different tests to predict significant scarring in the liver. This will inform us as to what strategy is best for future monitoring of patients on methotrexate.
We will also involve patients who are being considered for methotrexate therapy in this study as these have risk factors such as obesity and
diabetes which can themselves cause scarring in the liver. Comparison of patients who are on and not yet on methotrexate will allow us to estimate the excess risk particularly due to methotrexate which is still uncertain.
The PBC Genetics Study is a national effort to establish a PBC DNA
collection consisting of DNA samples from approximately 5000 patients with PBC. The DNA collection has already been used for a genome-wide association study (GWAS) of PBC. The next major analysis will be a genome wide association study of response to Ursodeoxycholic acid (UDCA).
Global sample size 20,000
The primary aim of the study is the identification of genetic variants associated with primary biliary cirrhosis.
Systemic IgG4 disease may affect multiple organs in the body, and is characterised by tissue infiltration with immunogglobulin G4 (IgG4)-positive plasma cells. The disease may affect the pancreas, the biliary tract, the lungs, the kidneys and other body organs.
There is little understanding of the natural history of the disease. The extent of the disease is currently unclear, diagnosis is based upon a combination of erological, radiological and histopathological findings. Once diagnosed treatment with corticosteriod results in rapid resolution of symptoms and signs, although relapse may occur on withdrawal.
This study aims to :
1) assess the natural history of IgG4 systemic disease and the response to treatment over time.
2) Investigate the pathogenesis of IgG4 disease – in particular to evaluate the phenotype and function of IgG4 producing B cells and determine immunological factors that drive the expansion of IgG4 subsets.
Participants will be recruited from the John Radcliff hospital, and other sites across the UK.
A cohort and database of patients with systemic IgG4 disease and a control group of patients (those with high serum IgG4 levels only, and diseases that mimic systemic IgG4 disease such as pancreatic cancer and primary sclerosing cholangitis) will be established. These subjects will be assessed annually. Medical details will be recorded and blood samples taken. Healthy volunteers will be recruited for comparative immunological studies and asked to provide a blood sample once.
This is an observational study with two main elements.
1) A prospective cohort study of 100 people newly diagnosed with AIH followed for 12 months and observed for biochemical response to treatment (group 1). Those with complete and incomplete response will be compared for element for the immune response hypothesised to be critical to the development of the complete responder phenotype, which may represent future therapeutic targets. Sampling at 2 and 4 weeks of treatment may identify markers of early or rapid response to treatment and allow early stratification of complete and
2) A case control study of 450 people with incomplete biochemical response to at least 12 months of treatment for AIH (group 2b) and 250 people with complete biochemical response (Group 2a). Groups will be compared for critical immune variables as above.
Hepatitis B (HBV) and C viruses (HCV) are infections of the liver and if not diagnosed and treated result in life threatening liver scarring (cirrhosis), liver cancer and end stage liver disease (ESLD). Previously, HBV & HCV have
been difficult to treat successfully. Advances in the available and emerging therapies mean HCV infection is potentially curable and HBV treatable. HBV & HCV rates are rising disproportionately in the UK, with ethnic minorities having more HCV related ESLD. Our experience shows a that large number of first generation South Asian (SA) patients present to our Liver Unit with advanced, untreated liver disease. This group typically have not engaged with health services.
Through pilot work we realised a lack of engagement by the SA population is due to cultural, language and educational barriers to disease awareness, testing and treatment. As set out by NICE, to prevent further death and disease spread we need to find new ways of informing this ‘hard to reach’ group.
In an earlier phase of our work we ran focus groups with the South Asian community to understand current knowledge, concerns and expectations amongst this population and then inform the production of an educational video. In this current phase of the work we plan to show this video in community settings as a feasibility for a randomized control trial to test whether it is successful in improving uptake of testing for viral hepatitis and to identify methodological issues, recruitment and retention figures.
Those who consent will complete pre-video questionnaires,watch the video and complete post video questionnaires. There will also be the option of dried blood spot testing for hepatitis on the day (or at a later date for those who wish more time to consider). Not all who watch the video are expected to undergo testing.