The Epidemiological, Clinical and Genetic Aspects of Chronic Pancreatitis in Ireland

Abstract

Abstract: The epidemiological, clinical and genetic aspects of chronic pancreatitis in Ireland - Hazel Maria Ní Chonchubhair. Introduction: Chronic pancreatitis is a progressive, inflammatory, malabsorptive disease of the pancreas which considerably affects patients’ well-being and quality of life. Chronic pancreatitis is a complex genetic disorder, characterised by signs and symptoms which differ between patients with similar aetiology. The associated health, social, and socioeconomic consequences of chronic pancreatitis experienced by patients necessitate frequent, recurrent access (care episodes) to both primary and secondary healthcare settings. The management of chronic pancreatitis is complex, fraught with difficulties, and a multidisciplinary approach to management is required, to manage symptoms and co-morbidities. Aim: The aims of this thesis were to examine the management of chronic pancreatitis in Ireland, to investigate the prevalence and aetiology of patients, to examine the prevalence of a known malabsorption-related complication - small bowel intestinal overgrowth, and to investigate the prevalence of common pancreatic gene mutations in patients with chronic pancreatitis. Methods: Four interrelated studies were designed. The first study utilised two surveys to examine the management of chronic pancreatitis by both hospital consultants and general practitioners (GPs). The second study evaluated the hospital-based prevalence of chronic pancreatitis in Ireland using the Hospital Inpatient Enquiry system (HIPE), a nationwide administrative database. A systematic review was conducted to identify studies reporting the prevalence of chronic pancreatitis worldwide. The third study used a case-control methodology to investigate the prevalence of small intestinal bacterial overgrowth in non-surgical chronic pancreatitis patients with pancreatic exocrine insufficiency (PEI) using glucose hydrogen breath testing (GHBT). The final study recruited patients with chronic pancreatitis of alcohol-associated and idiopathic aetiology to evaluate the presence of major pancreatic gene mutations. This study compared the findings in patients to a historic control database representative of the general population Results: The surveys examining the management of chronic pancreatitis revealed deficits in the management of chronic pancreatitis in both secondary and primary care, including lack of multidisciplinary team access, lack of access to dietetic care, and lack of knowledge and awareness of existing chronic pancreatitis management guidelines. These finding led to the development of the first primary care chronic pancreatitis guidelines for Ireland. The epidemiological study of chronic pancreatitis in Ireland found that the prevalence of chronic pancreatitis in Ireland was 11.6-13.0 per 100,000, and the accompanying systematic review found that this was consistent with the prevalence in other European countries undertaken using similar administrative database methodologies. Reports of SIBO prevalence amongst chronic pancreatitis are wide ranging. The prevalence of SIBO amongst Irish non-surgical chronic pancreatitis patients with PEI detected using glucose hydrogen breath testing was 15%, which is similar to other studies using this consensus methodology. Symptom improvement was documented in all patients following antibiotic therapy. Results from the genetic study revealed that almost 20% of patients with idiopathic and alcohol-associated chronic pancreatitis have pancreatic gene mutations. Patients with chronic pancreatitis have an almost four-fold higher risk of disease than controls. The frequency of SPINK1 N34S was present in 14% of patients which was significantly higher than controls and the odds ratio of disease in the presence of this mutation is almost 5-fold higher than the general public. Severe and mild CFTR cystic fibrosis-causing variants confer an increased risk of disease in patients when compared to controls. Conclusion: Results from these studies on the epidemiological, clinical and genetic aspects of chronic pancreatitis may be used for management protocols, service planning, policy, and resource allocation. It is hoped they will inform best practice, by contributing to the evidence-base, and ultimately improve the management of patients with chronic pancreatitis in Ireland and internationally.