Z Gastroenterol 2019; 57(06): 734-739
DOI: 10.1055/a-0825-2437
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Die primäre chologene Diarrhö in einer gastroenterologischen Praxis

Primary bile acid diarrhea in a community gastroenterology practice
Henrich Wenzel
BAG Wenzel/Spelter/Mallach, Wuppertal, Germany
› Author Affiliations
Further Information

Publication History

04 December 2018

13 March 2019

Publication Date:
15 April 2019 (online)

Zusammenfassung

Die primäre chologene Diarrhö (PCD) wurde bei ihrer Erstbeschreibung 1976 als sehr seltene Erkrankung angesehen, heute wird die Inzidenz auf > 1 % geschätzt. Das diagnostische Instrumentarium ist unterschiedlich verfügbar und es gibt in Deutschland keine einheitliche Empfehlung zur Diagnostik. Die PCD wird immer noch zu selten diagnostiziert.

Seit Anfang der 90er Jahre haben wir die Probebehandlung mit Colestyramin und anschließende Bestätigung durch den Gallensäureresorptionstest (SeHCAT-Test) mit einer 7-Tage-Retention von 20 % als Schwellenwert zum Nachweis der chologenen Diarrhö (CD) in unser diagnostisches Vorgehen aufgenommen.

Ausgewertet werden konnten 70 Patienten mit positiver Probebehandlung zwischen April 1991 und März 2017, von denen 60 mit SeHCAT-Test untersucht wurden. Nicht aufgenommen wurden Patienten mit CD Typ 1 oder Typ 3, ausgenommen Z. n. Cholezystektomie.

85 % (35/41) der Patienten mit PCD blieben bei einer Nachbeobachtungszeit von median 8,3 (1 – 23,6) Jahren behandlungsbedürftig, davon nahmen 68,6 % (24/35) Colestyramin, 31,4 % (11/35) andere Antidiarrhoika. 14,6 % (6/41) berichteten eine Spontanremission nach median 2,9 (0,7 – 5,7) Jahren.

In der Gruppe von Patienten mit CD nach Cholezystektomie waren 82 % (8/11) nach median 7,7 (1 – 24,5) Jahren weiter behandlungsbedürftig, 8 nahmen Colestyramin, ein Patient keine Medikamente, zwei Spontanremissionen.

Alle acht Patienten mit normalem SeHCAT-Test (7-Tage-Retention > 20 %) wurden nach median 3,6 (1,2 – 6,3) Monaten wieder beschwerdefrei.

Auch 70 % (7/10) der Patienten ohne Bestätigung durch den SeHCAT-Test waren nach median 4,3 (3,7 – 18,3) Jahren weiter behandlungsbedürftig.

Mit der Probebehandlung allein steht die Diagnose einer CD auf schwachen Füßen. Sie ist aber ubiquitär verfügbar und sollte im diagnostischen Algorithmus der chronischen Diarrhö einen festen Platz haben, wenn andere Verfahren nicht zur Verfügung stehen. Durch den primären Einsatz des SeHCAT-Tests ist nach aktueller Literatur eine deutlich höhere diagnostische Ausbeute zu erwarten und eine Einsparung unnötiger Folgeuntersuchungen möglich. Die therapeutischen Konsequenzen sind wegen der bekannten Limitationen des Colestyramin jedoch begrenzt. Eine besser verträgliche und zugelassene Alternative für Colestyramin wird dringend benötigt.

Abstract

When first described in 1976, primary bile acid diarrhea (BAD Type 1) was regarded as a very rare cause of chronic diarrhea. Today, the incidence is estimated as > 1 %. Availability of diagnostic tools varies widely and, in Germany, there is no generally consented recommendation for their use. BAD is still widely underdiagnosed.

Since the beginning of the ’90 s, we have added a therapeutic trial with cholestyramine to our diagnostic approach of chronic diarrhea. Patients with a positive test were offered a Selenium-homocholic acid taurine (SeHCAT) test for confirmation of bile-acid-diarrhea (BAD), using a 7-day-retention of 20 % as cut-off value.

From April 1991 to March 2017, after exclusion of other relevant causes for chronic diarrhea like IBD, celiac disease or microscopic colitis, 70 patients with a positive trial treatment of cholestyramine were identified for evaluation. Sixty of them had a SeHCAT test. Patients with BAD Type 1 and Type 3 were excluded, except for cholecystectomy.

85 % (35/41) of patients with BAD Type 1 needed continued medical treatment (median follow-up time 8.3 (1 – 23.6) years). Among them, 68.6 % (24/35) took cholestyramine, 31.4 % (11/35) loperamide or another antidiarrheal treatment. 14.6 % (6/41) of patients reported a spontaneous remission after median 2.9 (0.7 – 5.7) years.

In the group of patients with BAD after cholecystectomy, 82 % (8/11) still needed treatment after median 7.7 (1 – 24.5) years; 8 having taken cholestyramine, one patient nothing and two with spontaneous remissions.

All (8/8) patients with a normal SeHCAT test (7-day retention > 20 %) had spontaneous relief after median 3.6 (1.2 – 6.3) months.

Also, 70 % (7/10) of patients who had not been confirmed by the SeHCAT test still needed treatment after median 4.3 (3.7 – 18.3) years.

Based on a trial treatment alone, diagnosis of BAD is possible but not assured. Due to its ubiquitous availability, it should be used consequently if other methods are not available. Despite the well-known shortcomings of cholestyramine, a therapeutic trial should be used more consequently. According to the current literature, using the SeHCAT test in the first place will give significantly better results and unnecessary follow-up examinations can be avoided. However, therapeutic consequences might be modest due to the well-known limitations of cholestyramine. A well-tolerated and licensed alternative to cholestyramine is urgently needed.

 
  • Literatur

  • 1 Thaysen E, Hess PL. Idiopathic bile acid catharsis. Gut 1976; 965-970
  • 2 Sciarretta G, Furno A, Mazzoni M. et al. Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test. Am J Gastroenterol 1992; 87: 1852-1854
  • 3 Danielsson A, Nyhlin H, Persson H. et al. Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology. Gut 1991; 32: 1180-1187
  • 4 van Tilburg AJ, de Rooij FW, van den Berg JW. et al. Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane. Gut 1991; 32: 500-503
  • 5 Walters JRF, Tasleem AM, Omer OS. et al. A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis. Clin Gastroenterol Hepatol 2009; 7: 1189-1194
  • 6 Johnston IM, Nolan JD, Pattni SS. et al. Characterizing Factors Associated With Differences in FGF19 Blood Levels and Synthesis in Patients With Primary Bile Acid Diarrhea. Am J Gastroenterol 2016; 111: 423-432
  • 7 Reue K, Lee JM, Vergnes L. Diet1 is a Regulator of FGF15/19-dependent Bile Acid Synthesis. Dig Dis Basel Switz 2015; 33: 307-313
  • 8 Lee JM, Ong JR, Vergnes L. et al. Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants. Journal of Lipid Research 2018; 59: 429-438 . Im Internet: http://spiral.imperial.ac.uk/handle/10044/1/56154
  • 9 Merrick MV, Eastwood MA, Anderson JR. et al. Enterohepatic circulation in man of a gamma-emitting bile-acid conjugate, 23-selena-25-homotaurocholic acid (SeHCAT). J Nucl Med Off Publ Soc Nucl Med 1982; 23: 126-130
  • 10 Colestyramin-ratiopharm® Dosierbeutel. Im Internet: https://www.ratiopharm.de/produkte/praeparate-details/praeparate/praeparatedaten/detail/pzn-3740269.html
  • 11 Damsgaard B, Dalby HR, Krogh K. et al. Long-term effect of medical treatment of diarrhoea in 594 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study. Aliment Pharmacol Ther 2018; 47: 951-957
  • 12 Davidson MH, Dillon MA, Gordon B. et al. Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med 1999; 159: 1893-1900
  • 13 Puleston JMM, Andreyev J. New treatment for bile salt malabsorption. GUT 2005; 54: 441-442
  • 14 Beigel F, Teich N, Howaldt S. et al. Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn’s disease: A randomized, double-blind, placebo-controlled study. J Crohn’s Colitis 2014; 8: 1471-1479
  • 15 Bile acid malabsorption: colesevelam | Guidance and guidelines | NICE. Im Internet: https://www.nice.org.uk/advice/esuom22/chapter/Key-points-from-the-evidence
  • 16 Hvas CL, Ott P, Paine P. et al. Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature. World J Gastroenterol 2018; 24: 2320-2326
  • 17 Appleby R, Bajor A, Gillberg PG. et al. Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea. United Eur Gastroenterol J 2017; 5: 380-388
  • 18 Kruis W, Paumgartner G. Das Gallensäurenverlust-Syndrom. Deutsches Ärzteblatt 1982; 15: 33-36 . Im Internet: https://www.aerzteblatt.de/archiv/138819/Das-Gallensaeurenverlust-Syndrom
  • 19 Williams AJ, Merrick MV, Eastwood MA. Idiopathic bile acid malabsorption--a review of clinical presentation, diagnosis, and response to treatment. Gut 1991; 32: 1004-1006
  • 20 Wildt S, Nørby Rasmussen S, Lysgård Madsen J. et al. Bile acid malabsorption in patients with chronic diarrhoea: clinical value of SeHCAT test. Scand J Gastroenterol 2003; 38: 826-830
  • 21 Slattery SA, Niaz O, Aziz Q. et al. Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 2015; 42: 3-11
  • 22 Kurien M, Thurgar E. Challenging current views on bile acid diarrhoea and malabsorption. – PubMed – NCBI. Frontline Gastroenterol 2018; 9: 92-97
  • 23 Khalid U, Lalji A, Stafferton R. et al. Bile acid malabsoption: a forgotten diagnosis?. Clin Med 2010; 10: 124-126
  • 24 Arasaradnam RP, Brown S, Forbes A. et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018; gutjnl-2017-315909
  • 25 Camilleri M. Advances in understanding of bile acid diarrhea. Expert Rev Gastroenterol Hepatol 2014; 8: 49-61
  • 26 Fernández-Bañares F, Rosinach M, Piqueras M. et al. Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea. Aliment Pharmacol Ther 2015; 41: 1132-1140
  • 27 Lin S, Sanders DS, Gleeson JT. et al. Long-term outcomes in patients diagnosed with bile-acid diarrhoea. Eur J Gastroenterol Hepatol 2016; 28: 240-245
  • 28 Rössel P, Sortsøe Jensen H, Qvist P. et al. Prognosis of adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol 1999; 34: 587-590
  • 29 Watson L, Lalji A, Bodla S. et al. Management of bile acid malabsorption using low-fat dietary interventions: a useful strategy applicable to some patients with diarrhoea-predominant irritable bowel syndrome?. Clin Med Lond Engl 2015; 15: 536-540
  • 30 Jackson A, Lalji A, Kabir M. et al. The efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption – outcomes in patients previously treated for cancer. Clin Med Lond Engl 2017; 17: 412-418
  • 31 Fernández-Bañares F, Esteve M, Salas A. et al. Bile Acid Malabsorption in Microscopic Colitis and in Previously Unexplained Functional Chronic Diarrhea. Dig Dis Sci 2001; 46: 2231-2238
  • 32 Wedlake L, A’Hern R, Russell D. et al. 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: 707-717
  • 33 Wilcox C, Turner J, Green J. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther 2014; 39: 923-939
  • 34 Fernandes DCR, Poon D, White LL. et al. What is the cost of delayed diagnosis of bile acid malabsorption and bile acid diarrhoea?. Frontline Gastroenterol 2019; 10: 72-76
  • 35 Riemsma R, Al M, Corro Ramos I. et al. SeHCAT [tauroselcholic (selenium-75) acid] for the investigation of bile acid malabsorption and measurement of bile acid pool loss: a systematic review and cost-effectiveness analysis. Health Technol Assess Winch Engl 2013; 17: 1-236
  • 36 Hendy P, Florin T. Letter: therapeutic trial is more informative than SeHCAT to diagnose bile acid malabsorption. Aliment Pharmacol Ther 2015; 42: 780-780
  • 37 Slattery SA, Niaz O, Aziz Q. et al. Letter: therapeutic trial is more informative than SeHCAT to diagnose bile acid malabsorption – authors’ reply. Aliment Pharmacol Ther 2015; 42: 781-781
  • 38 Sehcat – Fachinformation. Im Internet: https://imedikament.de/sehcat/fachinformation
  • 39 Materialkosten SeHCAT-Test eine Kapsel 477 €, EBM-Ziffer 40554 Kostenpauschale 174,40 €. PD Dr. Tosch, persönliche Mitteilung. 2014
  • 40 Oduyebo I, Camilleri M. Bile acid disease: the emerging epidemic. Curr Opin Gastroenterol 2017; 33: 189-195