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Title: Biomarkers in the assessment and management of patients with chronic liver disease
Author: Fagan, Kevin
ISNI:       0000 0004 5922 3284
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2015
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Due to the rising prevalence of chronic liver disease (CLD) and its increasing burden on the health care system, the development and validation of biomarkers to aid in the assessment and management of patients is paramount. The aim of this thesis was to establish the need for biomarkers in patients with CLD and assess known and novel biomarkers that have been suggested for the assessment of alcohol intake, liver fibrosis and management of patients with decompensated cirrhosis. Alcohol, a significant primary and comorbid cause of liver injury, can impede therapeutic strategies or expedite disease progression. My work confirmed the need for an objective alcohol biomarker, corroborating previous findings that failure to recognise or acknowledge significant alcohol consumption remains common in clinical practice. Assessment of the most specific serum biomarker of sustained alcohol intake, carbohydrate deficient transferrin, demonstrated its poor sensitivity for detecting heavy alcohol consumption in patients with CLD, influenced by body mass index, gender and stage of liver fibrosis. Non-invasive detection and quantification of hepatic fibrosis is important in the identification, assessment and management of patients with CLD. The performance of the ELF test was assessed in a cohort of patients with CLD and demonstrated to be good at detecting advanced fibrosis using the manufacturer’s cut-off (?9.8). The performance of ELF test was negatively influenced by inflammation and age, but performed well in the presence of steatosis. This latter finding has not previously been described and is a significant finding in view of the global NAFLD epidemic. Patients with cirrhosis and ascites have a significant increase in morbidity and mortality and my work supports the need for better identification of patients with poor outcomes and coordination of patient care. Assessment of bacterial DNA, extracted from ascites, could replace culture based techniques and predict patients with poor outcomes. There was evidence of impaired innate immune function and the ascites bacterial communities reflected the intestinal dysbiosis that occurs patients with cirrhosis. Bacterial DNA may therefore further increase our knowledge of the pathogenesis of infection in cirrhosis and facilitate development of therapies and identification of other biomarkers for use in clinical practice. Overall the work in this thesis has proven the need for development and validation of biomarkers for the management of patients with CLD and highlighted future studies that may eventually lead to better clinical outcomes for patients with CLD.
Supervisor: Khakoo, Salim ; Powell, Elizabeth Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available