A third of patients with Inflammatory Bowel Disease (IBD) develop abnormal liver function tests (LFTs) at some point during their care. Over half of IBD patients are on thiopurines, which are not only a common cause of abnormal LFTs, but are also associated with a chronic liver disease, called nodular regenerative hyperplasia (NRH). The aim of this thesis was to determine the mechanisms and risk factors by which liver inflammation occurs in IBD, especially in relation to thiopurines. This thesis achieves its aim, firstly, through a large cohort study of patients with abnormal LFTs in IBD. Secondly, a candidate gene analysis is performed to determine which genes predispose to thiopurine hepatotoxicity. Thirdly, an assay is developed to measure compounds of the Methionine Cycle using mass spectrometry, to assess their role in thiopurine hepatotoxicity and as potential future biomarkers. Lastly, magnetic resonance elastography (MRE) is assessed as a potential screening modality to diagnose NRH. By providing novel answers as to the causes of liver inflammation in IBD, this thesis brings Medicine a step closer in preventing our patients from developing a common extraintestinal manifestation of their illness.
Liver inflammation in inflammatory bowel disease
Warner, B. (Author). 1 May 2020
Student thesis: Doctoral Thesis › Doctor of Medicine by Research