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Title: The influence of host factors on hepatic fibrosis and virolologic response in chronic hepatitis C infection
Author: Patel, Keyur
ISNI:       0000 0001 3475 7835
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2006
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Chronic hepatitis C (CHC) infection affects an estimated 170 million people worldwide, and is characterized by varying degrees of inflammation and progressive hepatic fibrosis leading to . cirrhosis and complications of end-stage liver disease in a proportion of patients over 20 to 40 years. CHC infection is now the leading indication for liver transplantation in developed nations. Several host and viral factors have been implicated disease progression and predicting response to therapy. The aims of this thesis were to characterize host determinants of progressive fibrosis and assess virologic responses in a large cohort ofCHC 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 responses to therapy in genotype-l infected patients. Myeloperoxidase gene polymorphisms also appear 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 ofCHC 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available