Medicine (St Vincent's) - Theses
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ItemClinical and scientific features of post-operative Crohn's disease recurrence( 2016)Crohn’s disease is a chronic relapsing inflammatory condition, primarily affecting the gut. It is associated with a significant reduction in health-related quality of life and significant healthcare costs. Up to 80% of patients will require surgery at some point in their life, but this is not curative, with Crohn’s disease recurring in most patients. The pathophysiology of Crohn’s disease relates to the mucosal immune response to antigenic stimulation of the gut microbiota, on a background in some patients of genetic susceptibility. “Dysbiosis” of the gastrointestinal microbiota has been implicated in the cause of Crohn’s disease but how the microbiota behaves in the post-operative state has not been examined in detail. This thesis involves a range of clinical and scientific studies that are part of the Post-operative Crohn’s Endoscopic Recurrence (POCER) platform of studies. These studies aimed to characterise the optimal management for patients after intestinal resection, with a view to preventing disease recurrence. My work has involved scientific studies aimed at identifying key microbial elements that may play a central role in recurrent disease, and further studies addressing optimised clinical management. I have studied gut tissue from patients taken longitudinally from the time of surgery till 18 months post-operatively, and from surgical and healthy controls. Using molecular microbial sequencing techniques I have defined a microbial profile associated with endoscopic recurrence of Crohn’s disease, identifying a novel association between the Proteus genus and recurrence. I have also confirmed that the presence of Faecalibacterium pruausnitzii is associated with a lesser rate of recurrence. Lastly I have shown that smoking, known to increase the rate of recurrence, is associated with a specific bacterial profile. The role of therapeutic monitoring of anti-tumour necrosis factor (TNF) drugs in the post-operative setting has been defined. Blood levels of anti-TNF drugs do not explain why the disease sometimes recurs on these medications. I have evaluated how the faecal biomarkers calprotectin, lactoferrin and S100A12 can be used to diagnose the presence and severity of post-operative Crohn’s disease recurrence. I have shown that calprotectin is a reliable marker of disease recurrence, and can be used as a substitute for colonoscopy. The effects of surgery, immunosuppression, routine early colonoscopy and disease activity on health-related quality of life and healthcare costs in the post-operative period have also been explored in this large and well-characterised post-operative cohort. This series of studies on post-operative Crohn’s disease treatment, monitoring and pathophysiology hold the prospect of changing the paradigm of post-operative care. They may also provide insights in the cause of disease recurrence.