Medicine (St Vincent's) - Theses
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ItemAn Australian population-based study of the incidence and outcomes of hepatocellular carcinoma: the Hepatomas of Melbourne Epidemiological Research (HoMER) study( 2019)Liver cancer, the world’s second highest cause of cancer death, is reportedly increasing in incidence in developed countries including Australia. Hepatocellular carcinoma (HCC), the predominant type of liver cancer, has a complex epidemiology involving the interplay of many dynamic risk factors including chronic viral hepatitis B and C, alcohol-related liver disease and non-alcoholic fatty liver disease. Recent trends in these risk factors, changes in Melbourne’s population demographics, together with advances in HCC diagnostics are thought to be increasing HCC incidence, although this may be currently underreported by the cancer registry. Accurate local epidemiology is required to inform healthcare policy for the appropriate allocation of resources for treatment, prevention and research that will improve clinical and economic outcomes. The major study of this thesis, to my knowledge, is the first in the world to determine the population incidence of HCC using clinical case capture independent of the cancer registry. In doing so, it is also the first study to validate the completeness and accuracy of a cancer registry in reporting HCC, which is critical given that the HCC epidemiology literature has been mostly dependent on local registry data. Over 12 months (July 2012 to June 2013), there were 272 new cases of HCC identified from multiple primary sources including multidisciplinary meeting reviews, hospital inpatient, outpatient and emergency attendance at any of Melbourne’s seven tertiary hospital networks, pathology, radiology and pharmacy databases. After cross- referencing with the Victorian Cancer Registry cases for the same period, the HCC incidence determined by this study was found to be twice as high as that reported by the registry. The recruited population-based prospective cohort of HCC patients then provided the opportunity to examine clinical outcomes across the breadth of presentation, demographics and institutional expertise. This allowed for the determination of factors associated with improved survival, in particular, the influence of HCC surveillance participation. The commonest risk factors for HCC were chronic hepatitis C (41%) and alcohol-related liver disease (39%) followed by chronic hepatitis B (22%). While participation rates were low (40%), surveillance was associated with earlier tumour stage at diagnosis, being offered curative therapies, and improved survival probability. In the era of advanced diagnostic imaging and therapeutics for HCC, only some of which is publicly funded, the economic cost of the HCC disease burden is an important consideration in cost-effectiveness analyses. This HCC incidence cohort provides the basis for the first direct costings study of HCC management in Australia, with associated clinical factors that determine high cost. The highest costs occurred at both of ends of the disease spectrum, with early stage disease curable by liver transplantation or surgical resection, as well as in the sickest patients with advanced disease and only palliative options available. Thus, investment of healthcare expenditure towards disease prevention and early detection would likely be most cost-effective with improved survival and reduced morbidity achieved. This world-first research, using a novel methodology for clinical case capture, determined the population-based incidence of HCC in Melbourne, confirmed the underreporting of incidence by the cancer registry and contributed to the correction of registry classification practices. For cancers with rapidly changing epidemiology such as HCC, accurate and contemporary local data is important in disease prevention and management and in guiding healthcare policy and research.