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Title: Single Nucleotide Polymorphisms of Mannan Binding Lectin and Complications of Chronic Liver Disease
Authors: Lo, Robert Su Chun
Supervisors: Freeman, Jan G.
Austin, Andrew
Award date: 6-Jun-2016
Presented at: University of Leicester
Abstract: Background: Mannan-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. Infection is a major complication in patients with chronic liver disease (CLD). Infection is also thought to lead to variceal bleeds. These complications cause significant mortality and morbidity. MBL single nucleotide polymorphisms (SNPs) may result in an inability to protect against pathogens which may contribute to the development of infection including spontaneous bacterial peritonitis (SBP). Association between MBL SNPs and SBP/variceal bleed is unclear. The aim of this thesis is to comprehensively assess the association of MBL SNPs and SBP/variceal bleed, and its role as a prognostic marker in liver related death. Methods: A case control study was performed. CLD patients with a prior history of complications (SBP/variceal bleed) were compared to those without. All patients were followed up subsequently in a longitudinal study to assess MBL SNPs as a risk factor for liver related death. Lastly, an open labelled proof of concept study was performed to determine the effect of 4 weeks probiotics therapy on bacterial translocation, systemic inflammation and the severity of liver disease. Results: No significant relationships were found between MBL SNPs and baseline inflammation or bacterial translocation. MBL SNPs was not a risk factor for the occurrence of SBP/variceal bleed in both the univariate and multivariate analaysis. In a Kaplan-Meier survival anaylsis, MBL SNPs was not associated with increased liver related death. MBL SNPs was also not an independent predictor in a multivariate Cox-regression analysis. The introduction of 4 weeks of probiotics therapy did not alter the baseline inflammation, bacterial translocation and severity of liver disease significantly. Conclusion: The results of this thesis suggest that MBL SNPs do not associate with the occurence of CLD complications (SBP/variceal bleed), and that MBL SNPs is not a prognostic marker for liver related death.
Type: Thesis
Level: Doctoral
Qualification: MD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Leicester Theses
Theses, Dept. of Cancer Studies & Molecular Medicine

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