Developing new predictors of Helicobacter pylori associated disease and its progression

White, Jonathan Richard (2017) Developing new predictors of Helicobacter pylori associated disease and its progression. PhD thesis, University of Nottingham.

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Abstract

Since discovery H. pylori has been one of the most intensively researched bacteria. Although the majority of those infected remain asymptomatic it can lead to serious diseases which carry significant morbidity and mortality. The most serious complication of H. pylori infection is gastric cancer and one of the most effective ways to reduce the associated mortality is to detect pre-malignant disease, as this develops in a step wise manner.

Using advanced endoscopy is one way to detect pre-malignant conditions but due to the variety in endoscopic techniques and mucosal classifications the diagnosis is often dependent on histology. This work aimed to develop simple, accurate classification systems to detect H. pylori associated disease. The sensitivity and specificity of magnification Narrow Band Imaging for detecting H. pylori gastritis was 69% and 67%, intestinal metaplasia 87% and 97% and dysplasia 92% and 98% respectively.

H. pylori is also associated with iron deficiency anaemia but the mechanisms remain unclear. In children it has been proposed that H. pylori disrupts iron regulatory mechanisms via the peptide hepcidin but this has not been extensively researched in adults. Serum hepcidin was significantly lower in H. pylori infected anaemic individuals and anaemic individuals without evidence of infection when compared to controls (9-fold, p=0.009 and 5-fold, p<0.0001 respectively). These results are opposite to data from children, possibly explained by the presence of gastric atrophy. The cellular localisation of ferroportin was different in the H. pylori infected group which could be due to local cytokine production. Gaining a better understanding of this mechanism could aid the development of more targeted investigation and treatment.

However, with regards to allergic and autoimmune conditions, there is growing evidence to suggest H. pylori is inversely associated. It is believed that any benefit associated with H. pylori is confined to childhood when the immune system is developing. A significant reduction was seen in IL10+ Tregs (p=0.0029) after successful eradication suggesting the removal of H. pylori may have systemic consequences on the immune system that are still not fully understood.

This work has highlighted the use of endoscopic techniques to identify individuals at risk of disease. It has also described the effects of eradication on the immune system which potentially could have implications for individuals with allergic conditions with regards to eradication therapy.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Atherton, J.
Robinson, K.
Ragunath, K.
Keywords: H. pylori, Endoscopy, Narrow band imaging, Eradication therapy
Subjects: W Medicine and related subjects (NLM Classification) > WC Communicable diseases
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 42983
Depositing User: White, Jonathan
Date Deposited: 11 Oct 2017 12:53
Last Modified: 14 Oct 2017 20:30
URI: http://eprints.nottingham.ac.uk/id/eprint/42983

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