The influence of host factors on hepatic fibrosis and virolologic [virologic] response in chronic hepatitis C infection
The influence of host factors on hepatic fibrosis and virolologic [virologic] response in chronic hepatitis C infection
The aims of this theses were to characterize host determinants of progressive fibrosis and assess virologic responses in a large cohort of CHC patients linked to an extensive and pedigreed biorepository. Our studies indicate that HLA class 1 allelic diversity has a relatively weak influence on disease severity and fibrosis progression compared to standard host factors such as age, gender and alcohol intake. However, steatosis is an important host variable that is associated with fibrosis, and also reduces both early and sustained virologic response to therapy in genotype-1 infected patients. Myeloperoxidase gene polymorphisms also appears to be associated with fibrosis severity, thus implicating oxidative stress in this regard. Non-invasive alternatives to a needle liver biopsy to stage and follow disease progression in CHC patients would be a useful clinical tool. We have developed and validated a serodiagnostic panel of matrix proteins to differentiate mild from moderate-to-severe stages of fibrosis that could provide an alternative to liver biopsy for binary disease staging in a proportion of CHC patients. At present, there are no reliable host, or viral, predictors of relapse following an end-of-treatment viral response. Our studies indicate that hepatic HCV RNA measurement has minimal clinical utility in following virologic responses to therapy, although residual intrahepatic virus may be present in a minority of patients that relapse following an apparent sustained virologic response. Whole blood extraction methods for viral detection also do not appear to provide any clinical benefit over conventional serum based assays during therapy, or in predicting relapse after an end-of-treatment response. Our ongoing studies will plan to better define the role of host immune response in hepatic injury, and develop accurate and reliable non-invasive markers of fibrosis.
University of Southampton
Patel, Keyur
9cf791fc-0932-420b-8899-0d78c1f66641
2006
Patel, Keyur
9cf791fc-0932-420b-8899-0d78c1f66641
Patel, Keyur
(2006)
The influence of host factors on hepatic fibrosis and virolologic [virologic] response in chronic hepatitis C infection.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The aims of this theses were to characterize host determinants of progressive fibrosis and assess virologic responses in a large cohort of CHC patients linked to an extensive and pedigreed biorepository. Our studies indicate that HLA class 1 allelic diversity has a relatively weak influence on disease severity and fibrosis progression compared to standard host factors such as age, gender and alcohol intake. However, steatosis is an important host variable that is associated with fibrosis, and also reduces both early and sustained virologic response to therapy in genotype-1 infected patients. Myeloperoxidase gene polymorphisms also appears to be associated with fibrosis severity, thus implicating oxidative stress in this regard. Non-invasive alternatives to a needle liver biopsy to stage and follow disease progression in CHC patients would be a useful clinical tool. We have developed and validated a serodiagnostic panel of matrix proteins to differentiate mild from moderate-to-severe stages of fibrosis that could provide an alternative to liver biopsy for binary disease staging in a proportion of CHC patients. At present, there are no reliable host, or viral, predictors of relapse following an end-of-treatment viral response. Our studies indicate that hepatic HCV RNA measurement has minimal clinical utility in following virologic responses to therapy, although residual intrahepatic virus may be present in a minority of patients that relapse following an apparent sustained virologic response. Whole blood extraction methods for viral detection also do not appear to provide any clinical benefit over conventional serum based assays during therapy, or in predicting relapse after an end-of-treatment response. Our ongoing studies will plan to better define the role of host immune response in hepatic injury, and develop accurate and reliable non-invasive markers of fibrosis.
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Published date: 2006
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Local EPrints ID: 466449
URI: http://eprints.soton.ac.uk/id/eprint/466449
PURE UUID: 661cec02-929b-4cd1-a372-46c06418c8e7
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Date deposited: 05 Jul 2022 05:17
Last modified: 23 Jul 2022 02:19
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Author:
Keyur Patel
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