SeHCAT

Abstract: Objective Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. Design We measured 75 Se-labelled homocholic acid-taurine ( 75 SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects ( 75 SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75 SeHCAT Results Compared with controls, patients with IBS had lower 75 SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p 75 SeHCAT retention ( 75 SeHCAT retention Conclusions Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.

Abstract: Background: Irritable bowel syndrome is a widespread disorder with a marked socioeconomic burden. Previous studies support the proposal that a subset of patients with features compatible with diarrhoea-predominant IBS (IBS-D) have bile acid malabsorption (BAM). Aims: To perform a systematic review and meta-analysis to assess the prevalence of BAM in patients meeting the accepted criteria for IBS-D. Methods: MEDLINE and EMBASE were searched up to March 2015. Studies recruiting adults with IBS-D, defined by the Manning, Kruis, Rome I, II or III criteria and which used 23-seleno-25-homotaurocholic acid (SeHCAT) testing for the assessment of BAM were included. BAM was defined as 7 day SeHCAT retention of <10%. We calculated the rate of BAM and 95% confidence intervals (CI) using a random effects model. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). Results: The search strategy identified six relevant studies comprising 908 individuals. The rate of BAM ranged from 16.9% to 35.3%. The pooled rate was 28.1% (95% CI: 22.6-34%). There was significant heterogeneity in effect sizes (Q-test χ2 = 17.9, P < 0.004; I2 = 72.1%). The type of diagnostic criteria used or study country did not significantly modify the effect. Conclusions: These data provide evidence that in excess of one quarter of patients meeting accepted criteria for IBS-D have bile acid malabsorption. This distinction has implications for the interpretation of previous studies, as well as contemporaneous clinical practice and future guideline development.

Abstract: Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7alpha-hydroxy-4-cholesten-3-one (7alphaHCO or 7alphaC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the (75)SeHCAT retention test. Our aim was to develop a serum 7alphaC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL(-1), sensitivity (lowest limit of detection 0.04 ng mL(-1)), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL(-1). There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7alphaC4 values, and identified increased 7alphaC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.