Prospective comparison of diagnostic tests for bile acid diarrhoea

Christian Borup; Lars Vinter-Jensen; Søren Peter German Jørgensen; Signe Wildt; Jesper Graff; Tine Gregersen; Anna Zaremba; Trine Borup Andersen; Camilla Nøjgaard; Hans Bording Timm; Antonin Lamazière; Dominique Rainteau; Svend Høime Hansen; Jüri Johannes Rumessen; Lars Kristian Munck

doi:10.1111/apt.17739

Prospective comparison of diagnostic tests for bile acid diarrhoea

Christian Borup^*, Lars Vinter-Jensen, Søren Peter German Jørgensen, Signe Wildt, Jesper Graff, Tine Gregersen, Anna Zaremba, Trine Borup Andersen, Camilla Nøjgaard, Hans Bording Timm, Antonin Lamazière, Dominique Rainteau, Svend Høime Hansen, Jüri Johannes Rumessen, Lars Kristian Munck

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

11 Citations (Scopus)

65 Downloads (Pure)

Abstract

BACKGROUND: Bile 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.

AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT.

METHODS: This 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.

RESULTS: Ninety-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.

CONCLUSIONS: Diagnosis 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.

Original language	English
Journal	Alimentary Pharmacology & Therapeutics
Volume	59
Issue number	1
Pages (from-to)	39-50
Number of pages	12
ISSN	0269-2813
DOIs	https://doi.org/10.1111/apt.17739
Publication status	Published - Jan 2024

Bibliographical note

Access to Document

10.1111/apt.17739Licence: CC BY-NC 4.0

Borup et al. (2024). Prospective comparison of diagnostic tests for bile acid diarrhoeaFinal published version, 605 KBLicence: CC BY-NC 4.0

AUB Link

Search for the material in Aalborg University Library's search engine

Cite this

Borup, C., Vinter-Jensen, L., Jørgensen, S. P. G., Wildt, S., Graff, J., Gregersen, T., Zaremba, A., Andersen, T. B., Nøjgaard, C., Timm, H. B., Lamazière, A., Rainteau, D., Hansen, S. H., Rumessen, J. J., & Munck, L. K. (2024). Prospective comparison of diagnostic tests for bile acid diarrhoea. Alimentary Pharmacology & Therapeutics, 59(1), 39-50. https://doi.org/10.1111/apt.17739

@article{16fe112797dd476c922c28ff50892b2e,

title = "Prospective comparison of diagnostic tests for bile acid diarrhoea",

abstract = "BACKGROUND: Bile 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.AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT.METHODS: This 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.RESULTS: Ninety-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.CONCLUSIONS: Diagnosis 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.",

author = "Christian Borup and Lars Vinter-Jensen and J{\o}rgensen, {S{\o}ren Peter German} and Signe Wildt and Jesper Graff and Tine Gregersen and Anna Zaremba and Andersen, {Trine Borup} and Camilla N{\o}jgaard and Timm, {Hans Bording} and Antonin Lamazi{\`e}re and Dominique Rainteau and Hansen, {Svend H{\o}ime} and Rumessen, {J{\"u}ri Johannes} and Munck, {Lars Kristian}",

note = "{\textcopyright} 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.",

year = "2024",

month = jan,

doi = "10.1111/apt.17739",

language = "English",

volume = "59",

pages = "39--50",

journal = "Alimentary Pharmacology & Therapeutics",

issn = "0269-2813",

publisher = "Wiley",

number = "1",

}

Borup, C, Vinter-Jensen, L, Jørgensen, SPG, Wildt, S, Graff, J, Gregersen, T, Zaremba, A , Andersen, TB, Nøjgaard, C, Timm, HB, Lamazière, A, Rainteau, D, Hansen, SH, Rumessen, JJ & Munck, LK 2024, 'Prospective comparison of diagnostic tests for bile acid diarrhoea', Alimentary Pharmacology & Therapeutics, vol. 59, no. 1, pp. 39-50. https://doi.org/10.1111/apt.17739

TY - JOUR

T1 - Prospective comparison of diagnostic tests for bile acid diarrhoea

AU - Borup, Christian

AU - Vinter-Jensen, Lars

AU - Jørgensen, Søren Peter German

AU - Wildt, Signe

AU - Graff, Jesper

AU - Gregersen, Tine

AU - Zaremba, Anna

AU - Andersen, Trine Borup

AU - Nøjgaard, Camilla

AU - Timm, Hans Bording

AU - Lamazière, Antonin

AU - Rainteau, Dominique

AU - Hansen, Svend Høime

AU - Rumessen, Jüri Johannes

AU - Munck, Lars Kristian

PY - 2024/1

Y1 - 2024/1

N2 - BACKGROUND: Bile 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.AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT.METHODS: This 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.RESULTS: Ninety-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.CONCLUSIONS: Diagnosis 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.

AB - BACKGROUND: Bile 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.AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT.METHODS: This 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.RESULTS: Ninety-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.CONCLUSIONS: Diagnosis 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.

UR - http://www.scopus.com/inward/record.url?scp=85173537905&partnerID=8YFLogxK

U2 - 10.1111/apt.17739

DO - 10.1111/apt.17739

M3 - Journal article

C2 - 37794830

SN - 0269-2813

VL - 59

SP - 39

EP - 50

JO - Alimentary Pharmacology & Therapeutics

JF - Alimentary Pharmacology & Therapeutics

IS - 1

ER -

Prospective comparison of diagnostic tests for bile acid diarrhoea

Abstract

Bibliographical note

Access to Document

AUB Link

Other files and links

Fingerprint

Cite this