Abstract
Aim
This thesis has four aims:
1. To provide a contemporary overview of the pathogenesis of acute diverticulitis.
2. To examine the health care burden of acute diverticulitis, including with long term
follow up.
3. To examine the association between statin use and risk of acute diverticulitis.
4. To examine the role of the colonic microbiome in the pathogenesis of acute
diverticulitis.
Method
A literature review was undertaken. A retrospective study of patients admitted to Christchurch Hospital with acute diverticulitis was performed to estimate the financial burden of acute diverticulitis, including with long term follow up. A retrospective study of patients admitted to Christchurch Hospital with acute diverticulitis, linked to PHARMAC data was performed to assess statins as a risk reducing agent. A prospective case control study was performed to assess the colonic microbiome of patients admitted to Christchurch Hospital with acute diverticulitis.
Results
Acute diverticulitis is a common condition with rising incidence. The understanding of its pathophysiology has evolved, and is now considered to arise through a process of dysregulated immune response to intestinal microbiota in a genetically susceptible individual.
In a cohort of 170 patients the health care cost associated with acute diverticulitis was NZD4814 per patient, and there is a significant proportion of expense incurred subsequent to the initial presentation. Cost was distributed disproportionately – high cost of care was associated with complicated disease, surgical intervention and length of stay.
In a population based case-control study statin use was not found to be associated with reduced risk acute diverticulitis.
Distinct microbiome changes were found in patients with acute diverticulitis in a prospective case control study. Individuals with acute diverticulitis showed lower diversity compared with controls, and had lower abundance of healthy commensal bacterial genera and higher abundance of several known pathogenic bacterial genera.
Conclusion
This thesis provides a contemporary overview of the pathogenesis of acute diverticulitis, outlining a multifactorial process. Environmental risk factors are hypothesised to influence the colonic microbiome, which in turn interacts with the host immune system, thereby influencing local and systemic inflammation. New evidence from this thesis supports this hypothesis with distinct microbiome compositional changes demonstrated in patients with acute diverticulitis. This opens up several areas for further research in prognostication and in risk reduction. One such class of risk reducing agents, statins, was not found to alter risk. The economic burden of this disease was found to be significant and long term, further emphasising the need for ongoing research in order to reduce this burden to our health system, and to individuals and their family.