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Meta-analysis identifies biomarkers for bile acid diarrhea in functional bowel disorders
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Mayo Clinic researchers have performed a systematic review and meta-analysis which identified three new tests that can serve as biomarkers for idiopathic bile acid diarrhea in patients with diarrhea-predominant functional bowel disorders.
“Since there is no current, generally available, gold standard method for diagnosis of bile acid diarrhea, it is not possible to estimate sensitivity and specificity or to test predictive values of the different tests,” Michael Camilleri, MD, AGAF, from the division of gastroenterology at the Mayo Clinic in Rochester, Minn., and colleagues wrote. “Therefore, our aim was to evaluate the diagnostic yield, defined as the prevalence of a positive test relative to established normal values in healthy controls, in order to appraise the potential of these tests to serve as biomarkers for BAD in patients with lower [functional bowel disorders] with diarrhea.”
Michael Camilleri
Their search of observational studies published up to May 2015 evaluating adults diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D) or functional diarrhea, or patients whose chronic diarrhea had no organic explanation, yielded 36 eligible studies involving a total of 5,028 patients.
Patients were diagnosed with bile acid diarrhea (BAD) using the established test, 75selenium homotaurocholic acid test (75SeHCAT) retention in 24 studies, and with new tests including fasting serum 7-alpha-hydroxy-4-cholesten-3-one (serum C4) in six studies, fasting serum fibroblast growth factor (FGF)19 in three studies, and 48-hour total fecal bile acid excretion in two studies.
The diagnostic yields of abnormal tests were highest for 75SeHCAT retention (< 10%) at 0.308 (95% CI, 0.247-0.377), followed by 0.171 (95% CI, 0.134-0.217) for serum C4, 0.248 (95% CI, 0.147-0.385) for serum FGF19 and 0.255 (95% CI, 0.071-0.606) for 48-hour total fecal bile acid excretion. Most analyses were associated with significant heterogeneity.
Overall, approximately 25% of patients with functional bowel disorders with diarrhea tested positive for bile acid diarrhea averaged over all studies and testing methods (30.8% for 75SeHCAT retention [<10%], 25.5% for total 48-hour fecal bile acid excretion, 24.8% for serum FGF19 and 17.1% for serum C4).
While some previous studies suggested there would be a high rate of BAD among these patients, this “uniform” finding that “about a quarter or a third of patients with unexplained diarrhea had evidence of BAD was surprising,” Camilleri told Healio Gastroenterology in an email. He therefore recommends that “all patients who do not respond optimally to first line, nonspecific treatment of IBS-D [or] functional diarrhea should be tested for BAD and if identified, treated with more specific therapy directed at the bile acid diathesis.”
Furthermore, he hopes that more convenient screening tests, particularly the serum C4 and FGF-19 tests, will be offered in the future. “If clinicians screen for celiac disease in patients with unexplained diarrhea, they should also start screening for BAD in the same patient group,” he concluded. – by Adam Leitenberger
Disclosures: This research is funded by NIH RO1 DK92179. The researchers report no relevant financial disclosures.
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