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Title: Tissue biomarkers of fibrosis progression in chronic hepatitis C infection
Author: Dolman, Grace E.
ISNI:       0000 0004 6347 3147
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2016
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Chronic infection with hepatitis C virus leads to liver fibrosis. In some individuals this can progress to cirrhosis and its clinical complications. As such, chronic hepatitis C is a major burden to healthcare systems globally. As fibrosis progression rates are highly variable, it would be useful to be able to identify those individuals at greatest risk of rapid progression. Efficacious therapies for hepatitis C are now available, but are expensive, and will not be available to all. Fibrosis progression is challenging to study due to the long duration of the disease. We have used data from the Trent Study of Patients with Hepatitis C Virus Infection to determine the factors associated with fibrosis progression in patients with advanced fibrosis and cirrhosis. This prospective cohort study contains a wealth of information and has ethical permission to collect clinical outcome data and access a large biobank of liver biopsies. Fibrosis progression is a non-linear process and our data suggest that the factors driving the process may change as fibrosis advances. We describe the development of a semi-automated digital image analysis algorithm to quantify collagen and elastin in archived liver biopsies and we have evaluated these tissue biomarkers as predictors of subsequent clinical outcomes. Elastin shows promise as a novel biomarker of progression to clinical outcomes in liver cirrhosis. Measuring gene expression profiles has the potential to be a sensitive indicator of fibrogenesis, not just fibrosis. We have measured the gene expression profile of archived hepatic biopsy tissue in patients with cirrhosis and we have identified a small number of target genes that have increased expression in those who reach clinical outcomes at 5 years. This work furthers our understanding of the factors that are predictive of progression to clinical outcomes in chronic hepatitis C infection, an area of increasing clinical importance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available