Medicine (St Vincent's) - Theses

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Type: Doctorate × Subject: natural history × Author: Croagh, Catherine Mary Nirmalee ×

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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.