2015University of Birmingham Institutional Research Archive (University of Birmingham)Requires access

Novel markers of liver fibrosis

Christopher Corbett

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Abstract

With chronic liver disease rising, the need to stage of liver disease and fibrosis accurately is paramount as it helps guide therapy and informs prognosis. Liver biopsy is a flawed gold standard, associated with morbidity and mortality. Application of simple non-invasive tests to assess fibrosis could provide a safe way of identifying patients in greatest need of intervention and of monitoring response to therapy. \n \nI have shown in this thesis that transient elastography is an excellent tool for ruling out significant fibrosis in patients with chronic liver disease. It is easy to learn and successful scanning correlates well with histological liver fibrosis. I have also shown that Use of APRI with a cut off of >1.5-2 and Fib-4 >3.25 can provide prognostic value for overall and liver-related mortality in patients with viral hepatitis. \n \nFinally I have assessed a range of potential new biomarkers showing that combining measuring serum levels of the chemokine CXCL10 and the endothelial adhesion receptor VAP-1 can increase the correlation strength with fibrosis stage. Using morphometric analysis of liver fibrosis I show that the same markers can be linked to quantitatively measured fibrosis, removing subjective bias and reducing inter and intra-operator variance in histological assessment. \n

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With chronic liver disease rising, the need to stage of liver disease and fibrosis accurately is paramount as it helps guide therapy and informs prognosis. Liver biopsy is a flawed gold standard, associated with morbidity and mortality. Application of simple non-invasive tests to assess fibrosis could provide a safe way of identifying patients in greatest need of intervention and of monitoring response to therapy. \n \nI have shown in this thesis that transient elastography is an excellent tool for ruling out significant fibrosis in patients with chronic liver disease. It is easy to learn and successful scanning correlates well with histological liver fibrosis. I have also shown that Use of APRI with a cut off of >1.5-2 and Fib-4 >3.25 can provide prognostic value for overall and liver-related mortality in patients with viral hepatitis. \n \nFinally I have assessed a range of potential new biomarkers showing that combining measuring serum levels of the chemokine CXCL10 and the endothelial adhesion receptor VAP-1 can increase the correlation strength with fibrosis stage. Using morphometric analysis of liver fibrosis I show that the same markers can be linked to quantitatively measured fibrosis, removing subjective bias and reducing inter and intra-operator variance in histological assessment. \n

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Available abstract

With chronic liver disease rising, the need to stage of liver disease and fibrosis accurately is paramount as it helps guide therapy and informs prognosis. Liver biopsy is a flawed gold standard, associated with morbidity and mortality. Application of simple non-invasive tests to assess fibrosis could provide a safe way of identifying patients in greatest need of intervention and of monitoring response to therapy. \n \nI have shown in this thesis that transient elastography is an excellent tool for ruling out significant fibrosis in patients with chronic liver disease. It is easy to learn and successful scanning correlates well with histological liver fibrosis. I have also shown that Use of APRI with a cut off of >1.5-2 and Fib-4 >3.25 can provide prognostic value for overall and liver-related mortality in patients with viral hepatitis. \n \nFinally I have assessed a range of potential new biomarkers showing that combining measuring serum levels of the chemokine CXCL10 and the endothelial adhesion receptor VAP-1 can increase the correlation strength with fibrosis stage. Using morphometric analysis of liver fibrosis I show that the same markers can be linked to quantitatively measured fibrosis, removing subjective bias and reducing inter and intra-operator variance in histological assessment. \n

Key concepts: Transient elastography, Fibrosis, Medicine, Liver biopsy, Liver fibrosis, Gold standard (test), Chronic liver disease, Liver disease

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