Savage, Anne Kay; (1996) The pathology of hepatitis C virus infection. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Hepatitis C virus is a recently discovered RNA virus which is an important cause of chronic liver disease around the world. This thesis explores several aspects of HCV-induced liver disease using the novel technique of RT-PCR on formalin-fixed, paraffin embedded histological material, and immunocytochemistry for detection of HCV antigen. The relationship of inflammation within the liver of HCV infected patients to HCV antigen expressing liver cells was investigated using these two techniques. This revealed no direct topographical relationship between inflammation and infected cells, although amount of inflammation within a sample was directly related to amount of HCV immunostaining. Numbers of cytotoxic T lymphocytes appeared inversely linked to the intensity of staining with anti-HCV antibody, implying a role for the immune system in the control of HCV infected cells. This role was supported by observations on HCV patients after liver transplantation. These showed that whilst HCV infection recurred after transplantation, the outcome varied between patients, possibly dependent on the immune status of individuals. HCV antigen expression can be greatly increased in these patients. The relationship between HCV infection and autoimmune hepatitis (AIH) was explored. It was found that most patients with type I AIH do not have HCV, but a small number of patients with significant levels of autoantibodies but a poor response to steroid treatment do have HCV infection. Finally, possible inapparent means of HCV transmission were explored by testing for HCV-RNA in extrahepatic sites post mortem. This study revealed that HCV-RNA can be detected in the salivary gland and seminal vesicle of HCV infected patients, as well as in the thyroid and pancreas. HCV antigen was detected in the salivary gland and thyroid in addition. These observations could help to explain possible non-parenteral or sexual transmission of HCV.

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