Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test

Christian Borup; Signe Wildt; Jüri Rumessen; Jesper Graff; Pierre Nordine Bouchelouche; Trine Borup Andersen; Lars Vinter-Jensen; Anna Zaremba; Søren Peter German Jørgensen; Tine Gregersen; Camilla Nøjgaard; Hans Bording Timm; Dominique Rainteau; Emilie Gauliard; Lars Kristian Munck

doi:10.14309/ajg.0000000000000772

Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test

Christian Borup, Signe Wildt, Jüri Rumessen, Jesper Graff, Pierre Nordine Bouchelouche, Trine Borup Andersen, Lars Vinter-Jensen, Anna Zaremba, Søren Peter German Jørgensen, Tine Gregersen, Camilla Nøjgaard, Hans Bording Timm, Dominique Rainteau, Emilie Gauliard, Lars Kristian Munck

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

The diagnosis of bile acid diarrhea is often missed because the availability of the ⁷⁵seleno-Taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test.METHODS:Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537).RESULTS:Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROC _AUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROC _AUCwas 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54).DISCUSSION:We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

Originalsprog	Engelsk
Tidsskrift	The American Journal of Gastroenterology
Vol/bind	115
Nummer	12
Sider (fra-til)	2086-2094
Antal sider	9
ISSN	0002-9270
DOI	https://doi.org/10.14309/ajg.0000000000000772
Status	Udgivet - dec. 2020

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10.14309/ajg.0000000000000772

Biochemical_Diagnosis_of_Bile_Acid_Diarrhea_.28Forlagets udgivne version, 432 KBLicens: CC BY-NC-ND

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Borup, C., Wildt, S., Rumessen, J., Graff, J., Bouchelouche, P. N., Andersen, T. B., Vinter-Jensen, L., Zaremba, A., German Jørgensen, S. P., Gregersen, T., Nøjgaard, C., Timm, H. B., Rainteau, D., Gauliard, E., & Munck, L. K. (2020). Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test. The American Journal of Gastroenterology, 115(12), 2086-2094. https://doi.org/10.14309/ajg.0000000000000772

@article{ae4d6675b9114f3fb72123364ffc6755,

title = "Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test",

abstract = "The diagnosis of bile acid diarrhea is often missed because the availability of the 75seleno-Taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test.METHODS:Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537).RESULTS:Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROC AUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROC AUCwas 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54).DISCUSSION:We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).",

author = "Christian Borup and Signe Wildt and J{\"u}ri Rumessen and Jesper Graff and Bouchelouche, {Pierre Nordine} and Andersen, {Trine Borup} and Lars Vinter-Jensen and Anna Zaremba and {German J{\o}rgensen}, {S{\o}ren Peter} and Tine Gregersen and Camilla N{\o}jgaard and Timm, {Hans Bording} and Dominique Rainteau and Emilie Gauliard and Munck, {Lars Kristian}",

year = "2020",

month = dec,

doi = "10.14309/ajg.0000000000000772",

language = "English",

volume = "115",

pages = "2086--2094",

journal = "The American Journal of Gastroenterology",

issn = "0002-9270",

publisher = "Wolters Kluwer Health",

number = "12",

}

Borup, C, Wildt, S, Rumessen, J, Graff, J, Bouchelouche, PN, Andersen, TB, Vinter-Jensen, L, Zaremba, A, German Jørgensen, SP , Gregersen, T, Nøjgaard, C, Timm, HB, Rainteau, D, Gauliard, E & Munck, LK 2020, 'Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test', The American Journal of Gastroenterology, bind 115, nr. 12, s. 2086-2094. https://doi.org/10.14309/ajg.0000000000000772

Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test. / Borup, Christian; Wildt, Signe; Rumessen, Jüri et al.
I: The American Journal of Gastroenterology, Bind 115, Nr. 12, 12.2020, s. 2086-2094.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Biochemical Diagnosis of Bile Acid Diarrhea

T2 - Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test

AU - Borup, Christian

AU - Wildt, Signe

AU - Rumessen, Jüri

AU - Graff, Jesper

AU - Bouchelouche, Pierre Nordine

AU - Andersen, Trine Borup

AU - Vinter-Jensen, Lars

AU - Zaremba, Anna

AU - German Jørgensen, Søren Peter

AU - Gregersen, Tine

AU - Nøjgaard, Camilla

AU - Timm, Hans Bording

AU - Rainteau, Dominique

AU - Gauliard, Emilie

AU - Munck, Lars Kristian

PY - 2020/12

Y1 - 2020/12

N2 - The diagnosis of bile acid diarrhea is often missed because the availability of the 75seleno-Taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test.METHODS:Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537).RESULTS:Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROC AUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROC AUCwas 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54).DISCUSSION:We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

AB - The diagnosis of bile acid diarrhea is often missed because the availability of the 75seleno-Taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test.METHODS:Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537).RESULTS:Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROC AUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROC AUCwas 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54).DISCUSSION:We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

UR - http://www.scopus.com/inward/record.url?scp=85097211468&partnerID=8YFLogxK

U2 - 10.14309/ajg.0000000000000772

DO - 10.14309/ajg.0000000000000772

M3 - Journal article

C2 - 32740083

SN - 0002-9270

VL - 115

SP - 2086

EP - 2094

JO - The American Journal of Gastroenterology

JF - The American Journal of Gastroenterology

IS - 12

ER -

Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test

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