S814 Bile Acid Malabsorption Is a Common Risk Factor for Diarrhea in Adults With Mucosal Healing in Crohn’s Disease

Abstract

Introduction: Bile acid malabsorption (BAM) accounts for over one-quarter of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and chronic diarrhea. However, the prevalence of BAM in adults with Crohn’s disease (CD) independent of ileal resection is not well characterized. We herein aim to identify the prevalence of BAM and determine its associations with diarrhea in adults with mucosal healing of CD on ileocolonoscopy. Methods: We analyzed a prospective cohort of adults with CD enrolled at a single institution biobank who underwent ileocolonoscopies from Jun 2014 to Mar 2021. Exclusion criteria were isolated upper GI CD (n=1) or prior bowel resection (n=9). Diarrhea was defined as an average of >3 liquid or very soft stools per day (SF>3) on the 2-item patient-reported outcome (PRO-2) measure over a 7-day period starting 48 hours before beginning bowel preparation. Endoscopic remission was defined as ≤2 on the Simple Endoscopic Score for Crohn's Disease (SES-CD). Histologic remission was defined as Geboes score < 2B.0 on biopsies from pre-determined ileocolonic segments (terminal ileum; ascending, descending, and rectosigmoid colon). Serum concentrations of 7α-hydroxy-4-cholesten-3-one (7C4), a precursor bile acid synthesis, were measured by liquid chromatography and mass spectrometry (Prometheus Laboratories) with BAM defined as a concentration ≥48.3 ng/mL (PMID: 30448597). We performed univariable analysis (χ2) and multivariable logistic regression to identify factors associated with diarrhea. Results: In 181 patients with CD in endoscopic remission, 29% (53/181) had diarrhea, and 29% (40/136) of those with 7C4 testing had BAM. Increased risk for diarrhea existed among those with BAM (OR 4.6, 95% CI 2.1-10.3, p< 0.01) and females (OR 2.2, 95% CI 1.1-4.3, p=0.02) (Table). On multivariate analysis, only BAM was a predictor of diarrhea (aOR 4.0, 95% CI 1.5-10.8, p< 0.01), but gender, ethnicity, and CD phenotype/location/duration were not predictors (Figure). Of the 57 patients with CD in endoscopic and histologic (endo-histologic) remission, BAM remains a risk factor for diarrhea (26%, 15/57; OR 35.8, 95% CI 6.9-184.2, p< 0.01). Conclusion: Bile acid malabsorption occurred in 29% and 26% of our cohort of adults with Crohn’s disease in endoscopic remission and endo-histologic remission, respectively, and conferred a 4-fold increased risk for diarrhea despite mucosal healing in Crohn’s disease.Figure 1.: Multivariable analysis of factor associated with diarrhea in adults with Crohn’s disease in endoscopic remission Key: aOR; adjusted odds ratio. CD, Crohn’s disease. Multivariable analysis of factor associated with diarrhea in adults with Crohn’s disease in endoscopic remission. Independent variables gender, ethnicity; CD phenotype, location, duration; and bile acid malabsorption. Dependent variable: diarrhea (SF >3) or diarrhea (stool frequency, SF >3). Table 1. - Crohn’s disease in Endoscopic remission (N=181) Characteristics n (%) Diarrhea (n=53) No Diarrhea (n=128) p-value OR (95% CI) p-value Gender 0.02 Female 36 (68%) 63 (49%) 2.2 (1.1-4.3) 0.02 Male 17 (32%) 65 (51%) Ref / Ethnicity 0.38 Caucasian Non-Caucasian 39 (74%) 101 (80%) 0.7 (0.3-1.5) 0.38 Missing n=1 14 (26%) 26 (20%) Ref / CD phenotype 0.08 Inflammatory Stricturing 18 (43%) 65 (63%) Ref / Fistulizing 12 (29%) 20 (19%) 2.2 (0.9-5.3) 0.0871 Missing n=36 12 (29%) 18 (17%) 2.4 (1.0-5.9) 0.0551 CD disease location Ileal Colonic Ileocolonic Missing n=22 0.14 22 (47%) 36 (32%) 1.5 (0.6-3.4) 0.38 14 (28%) 31 (28%) Ref / 12 (26%) 45 (40%) 0.6 (0.3-1.6) 0.33 CD duration 11 (21%)16 (31%)25 (48%) 31 (25%)51 (41%)43 (63%) 0.23 Ref0.9 (0.4-2.1)1.6 (0.7-3.8) /0.790.25 < 5 years 5-15 years >15 years Missing n=4 Bile acid malabsorption < 0.01 < 0.01 Yes No 22 (52%) 18 (19%) 4.6 (2.1-10.3) Missing n=45 20 (48%) 76 (81%) Ref Key: CD, Crohn’s disease; OR, odds ratio.