Doctor, Group Head / PI, Consultant Physician, Member of congregation and Supervisor
Whilst working as a Lecturer on the Liver Unit at the Royal Free Hospital under the supervision of Professor Dame Sheila Sherlock, I developed two main interests. Firstly, I studied various aspects of the effects of alcohol on iron metabolism, which formed the basis of my MD Thesis (Iron Metabolism in Liver Disease).
Secondly, I became interested in investigating the aetiology, clinical features and treatment of primary sclerosing cholangitis (PSC) and its relationship to liver dysfunction in inflammatory bowel disease.
Since moving to Oxford, I have maintained my interest in sclerosing cholangitis. At present we are investigating the hypothesis that the disease is immunologically mediated, perhaps triggered, by the development of a bacterial or viral infection.
In association with Prof Erik Schrumpf in Norway, I obtained a 3 year grant in1998 worth £200,000 from the EEC to form The European Study Group of PSC in order to promote European collaboration into PSC. The first meeting was held in Oslo in 1996. The group has been very successful with nine publications arising from joint projects.
The group continued to collaborate after an initial 3 year period and then expanded to take in other European groups interested in PSC. We have investigated the issue of crossover/overlap conditions between the various autoimmune liver diseases.
I am also a founder member of the International Autoimmune Hepatitis Group formed in 1992. This group remains active in organising international collaboration between research groups with a common interest in autoimmune liver diseases. Through this group I have been involved recently (2010) in producing a position paper regarding “Overlap Syndromes in autoimmune liver disease”.
We are currently studying the putative roles of retroviruses in the pathogenesis of autoimmune liver diseases, particularly PBC and PSC in collaboration with Dr Paul Klenerman. The role of immunogenetics and T regulatory cells on the development and course of the disease has been studied.
We have recently (2008) obtained funding (500,000 euros) from the Norwegian PSC research group (No- PSC) for a British genome wide scan into PSC; this involves the collection of DNA from 1000 PSC patients. In collaboration with Cambridge University I am also involved in a large UK GWAS study of PBC. We are collaborating with a number of other international centres including the Mayo Clinic in these large studies. I am also collaborating with Norway in a study of small duct PSC. In addition, we are proposing to obtain funding for a British GWAS study into Autoimmune Liver Disease. The British PSC support group provides regular annual funding (£10,00 per annum ) for research for our unit to continue our studies.
We have completed a study evaluating the presence of PSC in patients with total colitis and normal LFT’s using MRCP scanning. This has shown a high prevalence of PSC in otherwise clinical and biochemically normal patients with UC. This study has been extended to perform MRCP in UC patients with colonic dysplasia and cancer.
In addition, over the last decade we have carried several studies into the efficacy of high dose ursodeoxycholic acid (UDCA) in PSC both in the treatment of liver disease and the prophylaxis of colonic cancer.
The role of PSC and the effect of UDCA in colonic dysplasia is also being investigated in ulcerative colitis associated PSC and Crohn’s disease associated PSC. The natural history of pouch function in PSC pts who have undergone colectomy is also being evaluated, including quality of life (QoL) assessments.
A recent and expanding area of research for our group is IgG4 associated systemic disease with particular reference to its relationship to PSC. 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.
My group is also carrying out studies into Sphincter of Oddi dysfunction with regard to natural history, response to treatment, Quality of life (Q of L) assessments and prospective psychological studies.
In addition, I have been involved in various clinical trials, including assessing the role of and testing the efficacy of different agents in the treatment of luminal GI disorders including peptic ulceration, dyspepsia, reflux oesophagitis and irritable bowel syndrome. I am also closely currently involved in two international studies examining the role of a nuclear receptor agonist in the treatment of refractory Primary Biliary Cirrhosis (PBC).
Over the last 20 years, I have supervised 5 research fellows who have written successful doctoral theses for the Universities of Oxford and London. I am currently co supervising with Dr Ellie Barnes, a research fellow studying IgG4- related systemic disease.
Evolving role of magnetic resonance techniques in primary sclerosing cholangitis.
Selvaraj EA. et al, (2019), World journal of gastroenterology, 25, 644 - 658
Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.
Goode EC. et al, (2018), Hepatology
Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease.
Muir AJ. et al, (2018), Hepatology
Cost effectiveness of using ursodeoxycholic acid to treat primary biliary cholangitis.
Chapman RW., (2018), Br J Hosp Med (Lond), 79, 460 - 464
A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.
Kowdley KV. et al, (2018), Hepatology, 67, 1890 - 1902