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
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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.
