Medicine (St Vincent's) - Theses

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    Chronic hepatitis B in an Australian tertiary hospital cohort: natural history of disease and the association of viral markers with histological and serological outcomes
    Croagh, Catherine Mary Nirmalee ( 2015)
    Chronic Hepatitis B (CHB) is a major worldwide public health problem with an estimated 240 million people chronically infected and at risk of the complications of liver cirrhosis and hepatocellular carcinoma. There are recognized phases of disease in CHB which are usually defined using a combination of HBeAg status, HBV DNA level and ALT level. These can provide a useful framework to conceptualise a patient’s risk of fibrosis and need for treatment. Using the large CHB cohort at our tertiary hospital in Melbourne, we described our patient group in terms of their phase of disease in a cross-sectional analysis in chapter 3. This analysis highlighted some of the limitations of tests used, eg the insensitivity of older generation HBV DNA. Histological liver injury due to hepatitis B virus (HBV) was also able to be examined in a large proportion of our cohort with liver biopsies and in chapter 4 we evaluated the effect of HBV DNA on liver fibrosis. We found that increasing HBV DNA was associated with increasing prevalence of significant fibrosis in HBeAg negative patients, however in HBeAg positive patients, the reverse was true. This once again leads back to the concept of phase of disease in which HBeAg positive patients in the immune tolerant phase have normal ALT and minimal fibrosis despite very high HBV DNA levels. Longitudinal analysis of untreated HBeAg negative patients in chapter 5 brought to light some of the weaknesses of current classification systems for phase of disease, since we showed that low level fluxes in viral load in HBeAg negative patients were common and strict thresholds for HBV DNA to define the immune control phase were often crossed. The effects of HBV genotype and viral variants (precore and basal core promoter) on liver histology were examined in chapter 6. No significant associations were found although there was a trend towards higher prevalence of significant fibrosis in patients with HBV genotype C. Furthermore we explored the role of the novel markers of quantitative HBeAg and HBsAg (qHBeAg and qHBsAg) for classification of patients into phases in the natural history of CHB and found significant differences in qHBsAg levels in patients in different phases of disease in chapter 7. Finally we evaluated the role of qHBeAg and qHBsAg in the setting of Nucleos(t)ide analogue treatment by comparing 2 groups of HBeAg positive patients, one of which was known to lose HBeAg during the 18 months of followup and the other group which did not. Differences in both baseline and on treatment levels of qHBeAg were found between the 2 groups, however no significant differences in qHBsAg levels were noted. Management of CHB frequently involves monitoring patients to decide on the need and optimal time for therapy. A better understanding of the tools used in evaluating patients and the performance of these in different phases of disease and on therapy helps to enhance the clinical care of CHB patients.
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    Epidemiology, natural history and impact of inflammatory bowel disease in Australia
    Wilson, Jarrad Leigh ( 2010)
    The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract. International studies have demonstrated a dramatic rise in the incidence of these conditions over the past several decades. There are no corresponding studies from Australia to determine the local incidence. CD has been shown to have a complicated disease course, with high requirements for surgery and progression to disability. Psychological morbidity is also common, with a negative impact on health related quality of life. International studies have also demonstrated high direct and indirect health economic costs associated with CD. Australian data in each of these areas is either limited or totally absent. The aim of this work was to address the deficiencies in each of these key areas. The first Australian population-based study of IBD incidence was conducted prospectively over a one-year period in the region of Barwon. This utilised an extensive capture-recapture methodology, with near complete case identification and rigorous verification of diagnosed cases. The IBD incidence rates observed are among the highest reported in the world literature. The natural history of CD was then assessed in a retrospective, inception cohort study over a five-year period from the time of diagnosis. There was the progressive development of a more complicated disease phenotype, with high requirements for surgery. The results from surgery were not durable, with 60 percent needing escalation of therapy within 5 years. 41 percent of the cohort met the definition of disabling disease, with the presence of perianal fistulae at diagnosis highlighted as a key risk factor. This was followed by two cross-sectional, questionnaire-based, cohort studies to assess psychological health and health related quality of life (HRQoL) in CD. The first study was conducted in patients from the Inflammatory Bowel Disease Clinic at St. Vincent’s Hospital, Melbourne. The second was in a cohort of patients from the same institution who had required the formation of an ileostomy for CD. Both studies revealed high rates of depression, anxiety and poor HRQoL. These negative factors were contributed to by increased disease activity, but the strongest predictive factor was found to be the use of a negative, maladaptive coping style. Some patients with a stoma have adapted well, but others found it to be a negative experience, with ongoing concerns regarding sexuality and body image. The health economic costs of CD were then established using prospective cost diaries. Both direct and indirect costs were high, in keeping with the complicated natural history of CD. These studies highlight that IBD is common in Australia, and that CD has a complicated natural history, with negative impacts on psychological health and HRQoL, and with high economic costs. There is a need for increased public awareness as well as ongoing research and funding to improve clinical care.