Exploring the diagnostic tools for the assessment of liver fibrosis using biofluids
Exploring the diagnostic tools for the assessment of liver fibrosis using biofluids
The reference standard for the diagnosis of liver fibrosis is currently histological assessment of tissue obtained by liver biopsy. Whilst this provides valuable information it has limitations that include: being an invasive procedure, sampling error, observer variability and the use of categorical scoring systems.
This thesis focussed on non-invasive markers of liver fibrosis measured in biofluids and had three broad aims. Firstly, the evaluation of non-invasive markers in the literature in two major causes of liver disease, chronic hepatitis C (CHC) and non-alcoholic fatty live disease (NAFLD). Secondly, the exploration of how non-invasive markers could be used in clinical practice. Thirdly, the investigation of a novel technology to improve the diagnostic accuracy of non-invasive markers.
The systematic review highlighted the breadth of serum markers that are potentially available for the diagnosis of liver fibrosis and how the field has evolved from the use of single markers in NAFLD to panel markers in CHC. Simple markers, identified in the systematic review, were combined with a panel marker test to assess if diagnostic performance could be improved. A clinical utility model was developed to show how diagnostic test can be used in clinical practice. Using this model 86 % of liver biopsies could be avoided using a novel combination of panel markers for the diagnosis of severe fibrosis in NAFLD. The final part of the thesis explored how a technology platform, metabonomics, could aid the development of diagnostic markers. In this part of the study a number of signals were found to alter in early fibrosis, including mediators related to glucose metabolism. The potential to use metabonomics as a diagnostic is limited by practical considerations but it may have a role in highlighting critical pathways of disease.
Current non-invasive biomarkers have a role in the assessment of liver fibrosis and continuing to improve the accuracy and spectrum of diagnosis of non-invasive markers will increase the application of these tests in routine clinical practice.
University of Southampton
Guha, Indra Neil
1f743c7b-599b-40da-88cc-25c78db387f5
2007
Guha, Indra Neil
1f743c7b-599b-40da-88cc-25c78db387f5
Guha, Indra Neil
(2007)
Exploring the diagnostic tools for the assessment of liver fibrosis using biofluids.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The reference standard for the diagnosis of liver fibrosis is currently histological assessment of tissue obtained by liver biopsy. Whilst this provides valuable information it has limitations that include: being an invasive procedure, sampling error, observer variability and the use of categorical scoring systems.
This thesis focussed on non-invasive markers of liver fibrosis measured in biofluids and had three broad aims. Firstly, the evaluation of non-invasive markers in the literature in two major causes of liver disease, chronic hepatitis C (CHC) and non-alcoholic fatty live disease (NAFLD). Secondly, the exploration of how non-invasive markers could be used in clinical practice. Thirdly, the investigation of a novel technology to improve the diagnostic accuracy of non-invasive markers.
The systematic review highlighted the breadth of serum markers that are potentially available for the diagnosis of liver fibrosis and how the field has evolved from the use of single markers in NAFLD to panel markers in CHC. Simple markers, identified in the systematic review, were combined with a panel marker test to assess if diagnostic performance could be improved. A clinical utility model was developed to show how diagnostic test can be used in clinical practice. Using this model 86 % of liver biopsies could be avoided using a novel combination of panel markers for the diagnosis of severe fibrosis in NAFLD. The final part of the thesis explored how a technology platform, metabonomics, could aid the development of diagnostic markers. In this part of the study a number of signals were found to alter in early fibrosis, including mediators related to glucose metabolism. The potential to use metabonomics as a diagnostic is limited by practical considerations but it may have a role in highlighting critical pathways of disease.
Current non-invasive biomarkers have a role in the assessment of liver fibrosis and continuing to improve the accuracy and spectrum of diagnosis of non-invasive markers will increase the application of these tests in routine clinical practice.
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Published date: 2007
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Local EPrints ID: 466377
URI: http://eprints.soton.ac.uk/id/eprint/466377
PURE UUID: e90c26d2-e6ad-4931-a51d-73e7fcb843c8
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Date deposited: 05 Jul 2022 05:12
Last modified: 16 Mar 2024 20:40
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Author:
Indra Neil Guha
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