Haydon, Geoffrey Harold

2018-01-31T11:45:19Z

2018-01-31T11:45:19Z

1999

Infection with hepatitis C virus (HCV) is the cause of 90% of cases of non -A, non -B hepatitis. Chronic HCV hepatitis is at least initially an asymptomatic illness, but a proportion of patients will develop symptomatic, complicated disease. The most common complications are hepatic cirrhosis and hepatocellular carcinoma (HCC); presently it is unclear whether all infected patients will develop these complications.

AIMS OF THE THESIS There were two main aims. Firstly, to assess the clinical significance of staging investigations; in particular the significance of molecular virological investigations in terms of disease diagnosis and prognosis. The role of non- invasive investigations in staging the disease process was also considered. Secondly, to assess the impact of chronic hepatitis C infection was assessed in two populations; patients diagnosed as having hepatocellular carcinoma and those immunocompromised by chronic HIV infection.

MATERIALS AND METHODS A well characterised Scottish population of over 200 HCV infected patients was examined in detail to define the clinical significance and interpretation of serum 17 and intrahepatic hepatitis C virus levels, particularly in the context of biochemical, epidemiological, virological and histological parameters. The role of two non -invasive investigations in predicting the presence of hepatic cirrhosis was also assessed in these patients; firstly, a serum marker of perisinusoidal fibrosis, hyaluronic acid, and secondly, artificial neural network analysis of host and virus parameters.

Further, the impact of chronic HCV infection on two independent populations of patients was considered. Firstly, a population of 202 patients concurrently infected with the human immunodeficiency virus was examined in terms of clinical and immunological progression of disease. Secondly, the impact and association of chronic hepatitis C infection on the development of hepatocellular carcinoma in patients in Lothian (an area of low risk for the disease) over 10 years was investigated and compared with HCC associated with chronic HBV infection.

RESULTS In the Scottish population studied, both serum and intrahepatic virus levels were not determined by host factors (age of patient, mode or duration of infection) or by virus factors (HCV genotype). Likewise, there was no correlation between serum and liver HCV RNA levels demonstrated; however, these data did demonstrate that repetitive negative RT -PCR for HCV RNA in serum did not indicate absence of HCV from the liver. Pilot studies of the two non- invasive investigations, serum hyaluronic acid and ANN in this population showed both to be reliable in predicting the presence of hepatic cirrhosis.

Amongst the intravenous drug abusers with chronic HIV infection, HCV did not influence either the clinical progression of HIV disease to AIDS and it was not associated with a more rapid immunological decline. Chronic HCV infection was identified as a major risk factor for the development of hepatocellular carcinoma.

CONCLUSIONS Molecular virological staging investigations should be interpreted with caution in chronic HCV infection; their most significant role is likely to be the initiation and monitoring of therapy rather than the inference of disease prognosis. Non -invasive investigations of hepatic cirrhosis are likely to be useful tests to monitor disease progression especially when a liver biopsy is contraindicated, although they should be first validated in larger, well described populations.

http://hdl.handle.net/1842/28213

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 16

Already catalogued

The severity and activity of liver disease in chronic hepatitis C infection

Thesis or Dissertation

MD Doctor of Medicine