Mechanisms of Idiopathic Bile Acid Malabsorption and Diarrhoea

Bile acid malabsorption or diarrhea (BAM or BAD) is a syndrome of chronic watery diarrhoea diagnosed predominantly by a SeHCAT test and less commonly by measuring levels of 7-hydroxy-4-cholesten-3-one (C4) and furthermore responds to bile acid sequestrants (BAS). Primary bile acid diarrhoea (PBAD) is the condition with no definitive cause and is under diagnosed, often being labelled as IBS-diarrhoea with an associated burden of disease for patients. Recently an alternative mechanism for PBAD involving impaired Fibroblast Growth Factor (FGF19) production has been proposed. Aims: The primary aims were to prospectively recruit patients with chronic diarrhea, and define them into groups of BAD, or chronic diarrhoea with normal SeHCAT; characterisation with SeHCAT, C4 and serum FGF19; investigation of genetic differences involved in bile acid metabolism. Methods: 152 patients recruited had routine investigations for chronic diarrhoea including SeHCAT test. Fasting serum FGF19, C4 and bile acids levels were measured from blood samples and relationships examined; FGF19 optimisation, response of BAS on PBAD patients and on FGF19 levels, effect of bowel preparation & short bowel syndrome (SBS) on FGF19 levels were measured. 11 PBAD patients were studied through the day to examine variations in FGF19. 6 SNPs in genes involved in bile acid metabolism were analysed in PBAD patients. Results: Significantly lower fasting levels of FGF19 and increased levels of C4 were seen in patients with BAD with associations with Body Mass Index. Sensitivities and specificities for FGF19 against known tests were calculated. Excellent responses to BAS with no significant effect of bowel preparation on FGF19 and variable patterns during the day were seen. Reduced FGF19 levels were seen in SBS. SNPs studied in PBAD and control patients have yet to show any significant differences in frequencies. Conclusion: This research has confirmed that levels of an easily measurable and stable hormone, FGF19 are reduced in patients with BAD and is not affected by chronic diarrhoea per se. The work provides evidence of a disordered FGF19 production in PBAD patients, failing to reduce bile acid secretion and resulting in excess bile acids entering the colon causing BAD

Time to endoscopy for acute upper gastrointestinal bleeding: results from a prospective multicentre trainee-led audit

Background: Endoscopy within 24 hours of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24h of admission).Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between Nov-Dec 2017. Analyses were performed to identify factorsassociated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups.Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2h (IQR 12.0- 35.7), comprising median admission to referral and referral to endoscopy times of 8.1h (IQR 3.7- 18.1) and 6.7h (IQR 3.0-23.1) respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0% - 87.5%, p=0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7am-7pm or via the Emergency Department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1d; p= 0.004), but not 30-day mortality (p=0.344).Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome

Managing bile acid diarrhoea

Bowel symptoms including diarrhoea can be produced when excess bile acids (BA) are present in the colon. This condition, known as bile acid or bile salt malabsorption, has been under recognized, as the best diagnostic method, the 75 Se-homocholic acid taurine (SeHCAT) test, is not available in many countries and is not fully utilized in others. Reduced SeHCAT retention establishes that this is a complication of many other gastrointestinal diseases. Repeated studies show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an estimated population prevalence of around 1%. Recent work suggests that the condition previously called idiopathic bile acid malabsorption (BAM) is not in fact due to a defect in absorption, but results from an overproduction of BA because of defective feedback inhibition of hepatic bile acid synthesis, a function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach to treatment currently depends on binding excess BA, to reduce their secretory actions, using colestyramine, colestipol and, most recently, colesevelam. Colesevelam has a number of potential advantages that merit further investigation in trials directed at patients with bile acid diarrhoea

A Multicenter Study of Patient Acceptability of the IBD Disk Tool and Patient-Reported Disabilities.

BACKGROUND IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain patients' disabilities, we utilized the recently developed IBD Disk to help determine their functional concerns and initiate relevant conversation. We aimed to ascertain patient acceptability and their major disabilities. PATIENTS AND METHODS In this multicenter study, IBD patients at their outpatient visit were given the paper version of the IBD Disk. Patients were asked to score their level of disability for each item of the IBD Disk. The completed scores were then shared with their healthcare provider to act as a focus of discussion during the consultation. Patients and clinicians were also asked to provide informal qualitative feedback as to the benefits of the IBD Disk and areas for improvement. RESULTS A total of 377 (female 60%) patients completed the questionnaires over the study period. Patient acceptability scored on a 0-10 Likert scale was excellent. All patients scored all domains of disability. Sleep, energy, and joint pain were the highest scoring domains of the IBD Disk, scoring higher than digestive symptoms. Clinicians and patients agreed that the IBD Disk allowed for ease of communication about disability symptoms and relevance to their day-to-day functioning. CONCLUSION The IBD Disk is a novel easy-to-use tool to assess the functional disability of patients. We next plan to utilize it in the form of an electronic app internationally and in relation to treatment commencement and escalation