Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study

Abstract

Objectives: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test.

Methods: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4–8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results.

Results: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6–16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%,P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%,P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result.

Conclusions: The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

Keywords

bile acid diarrhea / cholestyramine / chronic diarrhea / SeHCAT test

References

[1] ArasaradnamRP,BrownS, ForbesA, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 2018;67(8):1380-1399.

[2] WilcoxC,TurnerJ, GreenJ. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther. 2014;39(9):923-939.

[3] KurienM,ThurgarE, DaviesA,Akehurst R,AndreyevJ. Challenging current views on bile acid diarrhoea and malabsorption. Frontline Gastroenterol. 2018;9(2):92-97.

[4] CamilleriM,Vijayvargiya P. The role of bile acids in chronic diarrhea. Am J Gastroenterol. 2020;115(10):1596-1603.

[5] MoneyME,Camilleri M. Review: management of postprandial diarrhea syndrome. Am J Med. 2012;125(6):538-544.

[6] WaltersJRF,TasleemAM, OmerOS,Brydon WG,DewT,le RouxCW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol. 2009;7(11):1189-1194.

[7] ScarpelloJH,HodgsonE, HowlettHC. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet Med. 1998;15(8):651-656.

[8] ShihaMG,AshgarZ, FraserEM,Kurien M,AzizI. High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria. EClinicalMedicine. 2020;25:100465.

[9] SlatterySA,NiazO, AzizQ,Ford AC,FarmerAD. Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther. 2015;42(1):3-11.

[10] AzizI,MumtazS, BholahH,Chowdhury FU,SandersDS,FordAC. High prevalence of idiopathic bile acid diarrhea among patients with diarrhea-predominant irritable bowel syndrome based on Rome III criteria. Clin Gastroenterol Hepatol. 2015;13(9):1650-1655.e2.

[11] FaniB,BertaniL, PaglianitiI, et al. Pros and cons of the SeHCAT test in bile acid diarrhea: a more appropriate use of an old nuclear medicine technique. Gastroenterol Res Pract. 2018;2018:2097359.

[12] TurnerJM,PattniSS, ApplebyRN,Walters JR. A positive SeHCAT test results in fewer subsequent investigations in patients with chronic diarrhoea. Frontline Gastroenterol. 2017;8(4):279-283.

[13] OrekoyaO,McLaughlin J,LeitaoE,JohnsW,LalS, PaineP. Quantifying bile acid malabsorption helps predict response and tailor sequestrant therapy. Clin Med (Lond). 2015;15(3):252-257.

[14] CostaS,GattoniS, NicolardiML, et al. Prevalence and clinical features of bile acid diarrhea in patients with chronic diarrhea. J Dig Dis. 2021;22(2):108-112.

[15] HendyP,FlorinT. Letter: therapeutic trial is more informative than SeHCAT to diagnose bile acid malabsorption. Aliment Pharmacol Ther. 2015;42(6):780.

[16] MearinF,LacyBE, ChangL, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393-1407.e5.

[17] WedlakeL,A’Hern R,RussellD,ThomasK,WaltersJRF, AndreyevHJN. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2009;30(7):707-717.

[18] BajorA,Törnblom H,RudlingM,UngKA,Simrén M. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut. 2015;64(1):84-92.

[19] BamptonPA,DinningPG, KennedyML,Lubowski DZ,CookIJ. The proximal colonic motor response to rectal mechanical and chemical stimulation. Am J Physiol Gastrointest Liver Physiol. 2002;282(3):G443-G449.

[20] MekjianHS,Phillips SF,HofmannAF. Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man. J Clin Invest. 1971;50(8):1569-1577.

[21] RaoAS,WongBS, CamilleriM, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139(5):1549-1558.e1.

[22] BaumgartnerM,LangM, HolleyH, et al. Mucosal biofilms are an endoscopic feature of irritable bowel syndrome and ulcerative colitis. Gastroenterology. 2021;161(4):1245-1256.e20.

[23] VasantDH,PainePA, BlackCJ, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021;70(7):1214-1240.

[24] LacyBE,Pimentel M,BrennerDM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44.

[25] MoayyediP,AndrewsCN, MacQueenG, et al. Canadian Association of Gastroenterology clinical practice guideline for the management of irritable bowel syndrome (IBS). J Can Assoc Gastroenterol. 2019;2(1):6-29.

[26] BarbaraG,CremonC, BelliniM, et al. Italian guidelines for the management of irritable bowel syndrome: Joint Consensus from the Italian Societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), General Medicine (SIMG), Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) and Pediatrics (SIP). Dig Liver Dis. 2023;55(2):187-207.

[27] Lupianez-MerlyC,Dilmaghani S,CamilleriM. Recent developments in diagnosing bile acid diarrhea. Expert Rev Gastroenterol Hepatol. 2023;17(12):1185-1195.

[28] BorupC,Vinter-Jensen L,JørgensenSPG, et al. Prospective comparison of diagnostic tests for bile acid diarrhoea. Aliment Pharmacol Ther. 2024;59(1):39-50.

RIGHTS & PERMISSIONS

2024 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.