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Viral persistence in hepatitus C virus infection

Viral persistence in hepatitus C virus infection
Viral persistence in hepatitus C virus infection

Hepatitis C virus (HCV) results in chronic infection in the majority of patients. The reason for viral persistence remains unknown. The aims of the thesis are firstly to study the natural history of HCV in order to establish what proportion of patients fail to clear HCV; secondly, to determine factors that might predict risk of developing chronic infection and rate of disease progression; thirdly, to determine underlying host and viral mechanisms that result in viral persistence.

Three different groups were studied: patients attending the Oxford hepatitis C clinic, patients identified as having been infected by contaminated blood by the Oxford blood centre and antibody deficient patients in the United Kingdom who were infected by a single HCV isolate from contaminated immunoglobulin. Each study group had different strengths: the first group represented a broad cross section of infected patients, in the second group the exact duration of infection was known and the third prospective study provided insight into the role of the immune system in determining disease outcome. In each study group, approximately 85% of patients failed to clear HCV spontaneously. Host factors appeared to be more important than viral factors in determining viral persistence; male sex and older age at infection being associated with viral persistence and worse disease outcome. Antibody deficiency did not increase the risk of developing chronic infection but significantly increased the rate of disease progression in chronically infected patients.

Different immune responses were seen in patients who cleared virus compared to those who developed chronic infection. In patients who cleared the virus, CD8+ T lymphocyte responses to HCV were found to be multi-specific compared to absent or oligospecific responses in patients who failed to eradicate HCV. In addition the T cell responses were phenotypically different with gamma interferon production mirroring cytotoxicity in patients with viral clearance but not in chronically infected patients. Finally, "escape mutation" by which the virus persists as a result of selection of HCV quasispecies containing mutations within immune epitopes does not appear to be the predominant mechanism by which the virus persists.

University of Southampton
Christie, John Michael Landale
b97eb8fd-1790-4d87-a8de-912bc1eb5960
Christie, John Michael Landale
b97eb8fd-1790-4d87-a8de-912bc1eb5960

Christie, John Michael Landale (2001) Viral persistence in hepatitus C virus infection. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Hepatitis C virus (HCV) results in chronic infection in the majority of patients. The reason for viral persistence remains unknown. The aims of the thesis are firstly to study the natural history of HCV in order to establish what proportion of patients fail to clear HCV; secondly, to determine factors that might predict risk of developing chronic infection and rate of disease progression; thirdly, to determine underlying host and viral mechanisms that result in viral persistence.

Three different groups were studied: patients attending the Oxford hepatitis C clinic, patients identified as having been infected by contaminated blood by the Oxford blood centre and antibody deficient patients in the United Kingdom who were infected by a single HCV isolate from contaminated immunoglobulin. Each study group had different strengths: the first group represented a broad cross section of infected patients, in the second group the exact duration of infection was known and the third prospective study provided insight into the role of the immune system in determining disease outcome. In each study group, approximately 85% of patients failed to clear HCV spontaneously. Host factors appeared to be more important than viral factors in determining viral persistence; male sex and older age at infection being associated with viral persistence and worse disease outcome. Antibody deficiency did not increase the risk of developing chronic infection but significantly increased the rate of disease progression in chronically infected patients.

Different immune responses were seen in patients who cleared virus compared to those who developed chronic infection. In patients who cleared the virus, CD8+ T lymphocyte responses to HCV were found to be multi-specific compared to absent or oligospecific responses in patients who failed to eradicate HCV. In addition the T cell responses were phenotypically different with gamma interferon production mirroring cytotoxicity in patients with viral clearance but not in chronically infected patients. Finally, "escape mutation" by which the virus persists as a result of selection of HCV quasispecies containing mutations within immune epitopes does not appear to be the predominant mechanism by which the virus persists.

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Published date: 2001

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Local EPrints ID: 464764
URI: http://eprints.soton.ac.uk/id/eprint/464764
PURE UUID: c04c9b9c-64d6-4d69-b52d-f820eb3a20b7

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Date deposited: 05 Jul 2022 00:00
Last modified: 23 Jul 2022 02:14

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Author: John Michael Landale Christie

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