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.

SUMMARY BackgroundBile acid diarrhoea is a common, under-diagnosed cause of chronic watery diarrhoea, responding to specific treatment with bile acid sequestrants. We previously showed patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile acid synthesis.

Further research into the precise mechanism of IBAM is needed. Improvements in the recognition of the condition and optimization of treatment are required.

OBJECTIVES:Increased colonic bile acids can cause chronic diarrhea. Bile acid diarrhea (BAD) is treatable by sequestrants, and may be secondary to ileal disease or primary BAD. It is underdiagnosed, partly because the selenium-75-homocholic acid taurine (SeHCAT) retention test is not available in many countries, and is underutilized in others. Serum 7α-hydroxy-4-cholesten-3-one (C4), a measure of bile acid synthesis, is available for diagnosis in specialist centers. Recently, deficiency of the ileal hormone fibroblast growth factor 19 (FGF19) has been shown in BAD. Our aim is to evaluate the diagnostic value of FGF19 in a large and prospective group of patients with chronic diarrhea, previously investigated with C4.METHODS:Patients undergoing routine investigation provided fasting blood samples. C4 was determined by high-performance liquid chromatography, and used to stratify two groups: group 1 (n=119), consisting of patients with normal C4 (≤ 28 ng/ml), and group 2 (n=139), consisting of patients with high C4 (>28 ng/ml), including any of the possible causes of BAD. Serum FGF19 was measured in stored samples by enzyme-linked immunosorbent assay.RESULTS:FGF19 and C4 were significantly inversely related (rs=−0.64, P<0.001). Patients with raised C4 had significantly lower median FGF19 values. Both of these were more marked when secondary to ileal disease, in particular ileal resection, than in primary BAD. The sensitivity and specificity of FGF19 at 145 pg/ml for detecting a C4 level >28 ng/ml were 58% and 79%, respectively. For C4 >60 ng/ml, these were 74% and 72% on receiver-operating characteristic analysis, the area under the curve was 0.80 (95% confidence interval 0.74–0.87).CONCLUSIONS:Serum FGF19 could be developed as a simple blood test to increase the diagnostic rates of BAD.

These studies demonstrate a complex, multifactorial etiology of PBAD, including impairments in ileal FGF19 expression and responsiveness.

Background: Endoscopy within 24 h 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 (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated 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 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p ¼ 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p ¼ 0.004), but not 30-d mortality (p ¼ 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.

Bile acid malabsorption occurs when there is impaired absorption of bile acids in the terminal ileum, so interrupting the normal enterohepatic circulation. The excess bile acids in the colon cause diarrhea, and treatment with bile acid sequestrants is beneficial. The condition can be diagnosed with difficulty by measuring fecal bile acids, or more easily by retention of selenohomocholyltaurine (SeHCAT), where this is available. Chronic diarrhea caused by primary bile acid diarrhea appears to be common, but is under-recognized where SeHCAT testing is not performed. Measuring excessive bile acid synthesis with 7α-hydroxy-4-cholesten-3-one may be an alternative means of diagnosis. It appears that there is no absorption defect in primary bile acid diarrhea but, instead, an overproduction of bile acids. Fibroblast growth factor 19 (FGF19) inhibits hepatic bile acid synthesis. Defective production of FGF19 from the ileum may be the cause of primary bile acid diarrhea.

BACKGROUNDThe current epidemiology of inflammatory bowel disease (IBD) in the multi-ethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago.AIMTo describe the incidence and phenotype of IBD and distribution within ethnic groups.METHODSAdult patients (> 16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database.RESULTSAcross a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis (UC, 64.3%), 115 with Crohn's disease (CD, 33.9%) and 6 with IBD unclassified (1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2/100000 and 20.5/100000) compared to White European (14.9/100000, P = 0.009 and 8.2/100000, P < 0.001) and Pakistani groups (14.9/100000, P = 0.001 and 11.2/100000, P = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans (52.7% vs 41.7%, P = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment.CONCLUSIONThis is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC (20.5/100000). Further studies on dietary, microbial and metabolic factors that might explain these findings in UC are underway.