S566 Evaluation of Secondary Bile Acids in Stool as Predictors of Chronic Bile Acid (BA) Diarrhea

Abstract

Introduction: Bile acid diarrhea (BAD) accounts for ∼25% of chronic “functional diarrhea” (FD). Diagnosis of BAD is currently based on serum 7αC4 >52ng/mL, total fecal BA (TBA) >2,337 µmol/48h, or fecal primary BAs [cholic acid (CA) and chenodeoxycholic acid (CDCA)] >10%. Secondary BAs [deoxycholic acid (DCA) and lithocholic acid (LCA)] are produced by 7α dehydroxylation of CA and CDCA, respectively. DCA promotes colonic secretion, serotonin release, and peristalsis. LCA is a potent stimulus of the Takeda G-protein coupled BA receptor (TGR5, or GPBAR1) which is a mechanism accelerating colonic transit. However, the utility of fecal secondary BAs (DCA and LCA) as markers of both diarrhea [increased fecal weight (FW)] and BAD is unclear. Methods: We conducted a retrospective study of fecal BA 48h data of 913 patients with FD and no prior intestinal surgery or active inflammatory disease. Patients consumed a 100g fat diet for four days with stool collection in the final 48h. Objective diarrhea was defined as FW >400 g/48h. Associations between TBA, main BA components, observed FW, or objective diarrhea (FW >400g/48h) were assessed using linear or logistic regression as appropriate. Multivariate analyses, adjusting for age, sex, and other fecal BAs, were conducted to appraise the role of each BA component. Results: Mean age was 51.5y (range: 11-90y), and 67.6% were female. Mean 48h FW was 546.1g (10-90%ile: 158-1056g). Mean TBA was 1921 µmol/48h (10-90%ile: 256-4328 µmol/48h). In the adjusted analyses, a 2-fold increase in CA and LCA was associated with 12.2% (95% CI: 7.4%-17.2%, p < 0.05) and 15.3% (7.9%-23.1%, p < 0.05) increases in FW, respectively. In contrast, a 2-fold increase in DCA was associated with a 6.8% (1.4%-11.9%, p < 0.05) decrease in FW. Table presents risk of FW >400g [OR (95% CI)] for a 2-fold increase in each BA (adjusted for age and sex) in all patients, and in 2 groups without or with BAD based on TBA >2,337 µmol/48h. The 48h total LCA conferred the greatest risk. In all patients, 48h fecal LCA of 360 µmol/48h had 46% sensitivity and 80% specificity for FW >400g (AUC=0.62, Figure). Adding total LCA to the prediction from total primary BAs increased the AUC from 0.75 to 0.78. Conclusion: Among patients presenting with FD, 48h fecal total LCA is associated with FW >400g with comparable risk estimates to total primary BAs and with CA alone. Therefore, fecal LCA also has potential utility in the diagnosis of BAD.Figure 1.: Receiver operating characteristic (ROC) curve for LCA as a predictor of objective diarrhea Table 1. - Estimated risk of diarrhea (fecal weight >400 g/48 hours) for 2-fold increase in bile acid component Bile Acid All patients(N=913) TBA < 2,337 µmol/48h(N=676) TBA > 2,337 µmol/48h(N=237) CA 1.34 (1.16-1.55)*** 1.22 (1.03-1.46)* 1.66 (1.11-2.49)* CDCA^ 0.98 (0.84-1.14) 0.95 (0.79-1.15) 0.73 (0.49-1.10) DCA^ 0.80 (0.67-0.95)* 0.82 (0.67-1.01) 0.51 (0.34-0.76)** LCA 1.47 (1.20-1.80)*** 1.34 (1.06-1.69)* 2.12 (1.41-3.19)*** UDCA 1.07 (0.99-1.15) 1.11 (1.02-1.22)* 0.91 (0.75-1.11) TBA=total fecal bile acid; UDCA=ursodeoxycholic acid.^secretory BA.*p<0.05.**p<0.01.***p<0.0005.