Perspectives in clinical gastroenterology and hepatologyMethods for Diagnosis of Bile Acid Malabsorption in Clinical Practice
Section snippets
Clinical Utility
The 14C-glycocholate breath and stool test is a method to determine bacterial-dependent deconjugation within the gastrointestinal tract, which is due to bacterial overgrowth in the small bowel or BAM.15, 16
The 14C-glycocholate solution is orally administered and incorporates into the intraluminal pool of BAs. Bacteria can enzymatically cleave the bond between CA and glycine. 14C-glycine is released, absorbed into the portal circulation, and rapidly metabolized in the liver, and the end product
Clinical Utility
75SeHCAT uses a synthetic 75selenium homotaurocholic BA that is resistant to bacterial degradation21 and passive diffusion.22 Thus, 75selenium homotaurocholic BA can be either actively absorbed in the terminal ileum to enter the enterohepatic circulation or excreted into stool, unaltered by its passage through the colon.
Unlike 14C-glycocholate, 75selenium decays through gamma emission and thus can be measured with an external counter, a gamma camera, which does not require a collimator,
Clinical Utility
C4 was initially developed to measure BA synthesis and the associated removal of circulating low-density lipoprotein cholesterol in clinical trials investigating modalities to reduce cardiovascular risk.27 BA synthesis occurs via neutral and acidic pathways. In humans, 90% of BA synthesis occurs through the neutral pathway, which is regulated by the rate-limiting enzyme cholesterol 7α hydroxylase (CYP7A1). C4 is a downstream product of CYP7A1 (Figure 2). The correlation of C4 with BA synthesis
Clinical Utility
Apart from the fecal measurement of 14C-glycocholate, the tests discussed above indirectly assist in the diagnosis of BAM by measuring BA synthesis or retention. In contrast, it is now possible to quantify fecal total and individual BA. Increased total fecal BAs is reported in patients with chronic functional diarrhea31; moreover, recent data show that functional diarrhea and diarrhea-predominant IBS are associated with higher fecal levels of secretory BAs (CA,CDCA, DCA), whereas functional
Cross-validation of Methods to Detect Bile Acid Malabsorption
A number of studies published in the literature describe cross-validation between the various methods described; the comparative data are shown in Figures 4 and 5. Figure 4A compares 75SeHCAT retention at 3 days with total fecal BAs. The decrease in 75SeHCAT retention at day 3 is significantly associated with an increase in fecal BAs. After these initial validation studies in which the cutoff at 3 days was 34% retention, subsequent studies focused on the 75SeHCAT retention at 7 days and
Conclusions
Currently, 75SeHCAT retention, serum C4, and fecal BA measurements are the 3 viable tests available to diagnose BAM. Unfortunately, 75SeHCAT is not available in several countries, including the United States. Serum C4 is a simple and accurate method for patients who do not have liver disease or take statins and maintain a normal circadian rhythm; however, it has been studied in relatively small numbers of patients, and further validation, including response to therapy in patients selected for
Acknowledgments
The authors thank Mrs Cindy Stanislav for excellent secretarial assistance.
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This article has an accompanying continuing medical education activity on page e74. Learning Objectives-At the end of this activity, the successful learner will be able to analyze information about tests used to diagnose BAM and interpret results of these tests to diagnose BAM in patients presenting with chronic diarrhea.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by grant RO1-DK92179 (to Dr Camilleri) from National Institutes of Health.