Prospective comparison of diagnostic tests for bile acid diarrhoea

Abstract

SummaryBackgroundBile acid diarrhoea is often missed because gold standard nuclear medicine tauroselcholic [75‐Se] acid (SeHCAT) testing has limited availability. Empirical treatment effect has unknown diagnostic performance, whereas plasma 7α‐hydroxy‐4‐cholesten‐3‐one (C4) is inexpensive but lacks sensitivity.AimsTo determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT.MethodsThis diagnostic accuracy study was part of a randomised, placebo‐controlled trial of colesevelam. Consecutive patients with chronic diarrhoea attending SeHCAT had blood and stool sampled. Key thresholds were C4 > 46 ng/mL and SeHCAT retention ≤10%. A questionnaire recorded patient‐reported empirical treatment effect. We analysed receiver operating characteristics and explored machine learning applied logistic regression and decision tree modelling with internal validation.ResultsNinety‐six (38%) of 251 patients had SeHCAT retention ≤10%. The effect of empirical treatment assessed with test results for bile acid studies blinded had 63% (95% confidence interval 44%–79%) sensitivity and 65% (47%–80%) specificity; C4 > 46 ng/mL had 47% (37%–57%) and 92% (87%–96%), respectively. A decision tree combining C4 ≥ 31 ng/mL with ≥1.1 daily watery stools (Bristol type 6 and 7) had 70% (51%–85%) sensitivity and 95% (83%–99%) specificity. The logistic regression model, including C4, the sum of measured stool bile acids and daily watery stools, had 77% (58%–90%) sensitivity and 93% (80%–98%) specificity.ConclusionsDiagnosis of bile acid diarrhoea using empirical treatment was inadequate. Exploration suggested considerable improvements in the sensitivity of C4‐based testing, offering potential widely available diagnostics. Further validation is warranted. ClinicalTrials.gov: NCT03876717.

Risk of cancer in patients with bile acid diarrhoea: a Danish nationwide matched cohort study

“…However, we recently reported the false positive rate of such an approach as high as 35% and such misclassification would dilute out differences between cases and controls. 24 Lastly, although we used nationwide registries, the number of patients with BAD and associated cancer events was relatively low. An expert opinion estimates a 1% prevalence of BAD by extrapolating data from cohorts of copyright.…”

Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine

“…It is worth mentioning that current research has proposed a combination of fecal bile acid measurements and serum C4 measurements for diagnostic purposes [3,65]. A recent study revealed that the combination of C4 detection with ≥1.1 daily watery stools (Bristol type 6 and 7) had 70% (51-85%) sensitivity and 95% (83-99%) specificity, the logistic regression model including C4, the sum of measured stool bile acids and daily watery stools, had 77% (58-90%) sensitivity and 93% (80-98%) specificity, suggesting considerable improvements in the sensitivity of C4-based testing [66]. However, there is an urgent need to establish diagnostic criteria, which necessitates further in-depth research.…”

“…Moreover, optimization of measurement methods for fecal bile acid and serum C4, including sampling times, is necessary to enhance their accuracy and repeatability. Additionally, machine learning techniques and other approaches can be employed to develop models predicting the occurrence and severity of BAD based on results from fecal bile acid and serum C4 measurements with support from database algorithms [66,67].…”

Editorial: Bile acid diarrhoea – simplified clinico‐biochemical diagnosis

“…Borup et al 10 conducted a study in 251 consecutive patients (without inflammatory bowel disease or microscopic colitis) undergoing 75 SeHCAT scanning. In this cohort, 38% had <10% retention (at least moderate BAD).…”

“…The authors conducted a cross‐tabulation and receiver operating characteristics analysis, logistic regression and decision tree modelling of the diverse individual or combined tests relative to SeHCAT retention ≤10% as gold standard, using 60% of the cohort for model derivation and 40% for validation. The Table 1 10 provides performance characteristics of the diverse tests.…”