T1247 Effects of Chenodeoxycholic Acid On Gastrointestinal and Colonic Transit and Bowel Function in Healthy Volunteers

Abstract

INTRODUCTION: Epidemiologic evidence suggests a link between gastro-esophageal reflux disease (GERD) and obesity. Studies suggest that this relationship is due to the effects of central adiposity on intragastric pressure with disruption of the gastro-esophageal junction (GEJ) reflux barrier, however the clinical relevance of these findings has not been proven. METHODS: From Aug 2005 to Dec 2006, patients sent to a referral center for physiologic investigation of GERD were studied. Height, weight and waist circumference (WC) were measured. Stationary manometry and 24hr ambulatory pH studies off acid-suppressants were performed and symptom severity was assessed by a validated questionnaire. Linear regression models were used to analyze associations between covariates of interest and Pearson's correlation coefficient (PC) was applied to assess the strength of association. RESULTS: 582/676(86%) consecutive patients (age 48 (range 14-89), 56% female) had complete data for analysis. The prevalence of obesity defined by BMI≥30kg.m-2 in males and females was 16% and 23% (p=ns) respectively. More men hadWC≥99cm (M41%:F28%; p<0.001)). %time pH<4 at 5cm above the lower esophageal sphincter (LES) increased with obesity (PC=0.255 and 0.240 for BMI and WC respectively; both p<0.001) and age (PC= 0.162; p<0.001) and was higher in men than women (p=0.014) Increase in %time pH<4 was associated with a reduction in LES pressure and abdominal LES length (PC=-0.327, -0.344 respectively; p<0.001). There was a weak negative association of BMI with LES pressure (PC=-0.140; p=0.005) but no link with abdominal LES length. In contrast, there was a significant negative association of WC with LES pressure (PC=-0.225; p<0.001) and abdominal LES length (PC=-0.213; p<0.001). Overall symptom severity increased with %time pH<4 (PC=0.209; p<0.001); however there was no change in symptom severity with BMI (PC=0.056, p=0.17) and the effect of WC was weak and of borderline significance (PC=0.083, p=0.05). CONCLUSION: In this large cohort of clinical patients referred for investigation of reflux symptoms, gastro-esophageal reflux increased with obesity and was most prevalent in elderly males with central adiposity. WC but not BMI was associated with both reduced LES pressure and abdominal length. These findings confirm the mechanistic link between increasing WC and the risk of reflux via raised intragastric pressure and disruption of the GEJ. In contrast, there was little change in symptom severity despite increased acid exposure in this group. The relative insensitivity to acid reflux may explain the increased prevalence of severe and complicated reflux in obese patients.