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Canadian Association of Gastroenterology Clinical Practice Journal of the Canadian Association of Gastroenterology, 2020, 3(1), e10–e27 SubBList2=BList=SubBList=BList doi: 10.1093/jcag/gwz038 HeadB/HeadA=HeadC=HeadB/HeadA=HeadC/HeadB Original Article HeadC/HeadB=HeadD=HeadC/HeadB=HeadC/HeadB Advance Access publication 6 December 2019 HeadC=NList_dot_numeric1=HeadC=NList_dot_numeric HeadC/HeadB=NList_dot_numeric1=HeadC/HeadB=NList_dot_numeric Original Article HeadD=NList_dot_numeric1=HeadD=NList_dot_numeric HeadD/HeadC=NList_dot_numeric1=HeadD/HeadC=NList_dot_numeric Canadian Association of Gastroenterology Clinical Practice SubBList2=NList_dot_numeric2=SubBList=NList_dot_numeric2 Guideline on the Management of Bile Acid Diarrhea SubBList2=NList_dot_numeric=SubBList=NList_dot_numeric 1 2 3 4 4 NList_dot_numeric2=HeadB=NList_dot_numeric=HeadB Daniel C. Sadowski , Michael Camilleri , William D. Chey , Grigorios I. Leontiadis , John K. Marshall , 5 4 6 Downloaded from https://academic.oup.com/jcag/article-abstract/3/1/e10/5661094 by guest on 26 March 2020 NList_dot_numeric3=HeadB=NList_dot_numeric=HeadB Eldon A. Shaffer , Frances Tse , Julian R. F. Walters NList_dot_numeric2=SubBList1=NList_dot_numeric=SubBList1 1Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada; 2Division of Gastroenterology 3 NList_dot_numeric3=SubBList1=NList_dot_numeric=SubBList1 and Hepatology, Mayo Clinic, Rochester, Minnesota, USA; Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA; 4Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, SubBList3=HeadD=SubBList_Before_Head=HeadD McMaster University, Hamilton, Ontario, Canada; 5Division of Gastroenterology, University of Calgary, Calgary, Alberta, SubBList2=HeadD=SubBList_Before_Head=HeadD Canada; 6Division of Digestive Diseases, Imperial College London, London, UK SubBList2=HeadB=SubBList=HeadB Correspondence: Daniel C. Sadowski, MD, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, T6G 2X8, SubBList3=HeadB=SubBList=HeadB Canada, e-mail: [email protected] HeadC=NList_dot_numeric1(2Digit)=HeadC=NList_dot_numeric(2Digit) HeadC/HeadB=NList_dot_numeric1(2Digit)=HeadC/HeadB=NList_dot_numeric(2Digit) Abstract HeadD=NList_dot_numeric1(2Digit)=HeadD=NList_dot_numeric(2Digit) Background and Aims: Chronic diarrhea affects about 5% of the population overall. Altered bile HeadD/HeadC=NList_dot_numeric1(2Digit)=HeadD/HeadC=NList_dot_numeric(2Digit) acid metabolism is a common but frequently undiagnosed cause. SubBList2(2Digit)=NList_dot_numeric2(2Digit)=SubBList(2Digit)=NList_dot_numeric2(2Digit) Methods: We performed a systematic search of publication databases for studies of assessment and SubBList2(2Digit)=NList_dot_numeric(2Digit)=SubBList(2Digit)=NList_dot_numeric(2Digit) management of bile acid diarrhea (BAD). The certainty (quality) of evidence and strength of recom- NList_dot_numeric2(2Digit)=HeadB=NList_dot_numeric(2Digit)=HeadB mendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Patient population, intervention, comparator and outcome questions were de- NList_dot_numeric3(2Digit)=HeadB=NList_dot_numeric(2Digit)=HeadB veloped through an iterative process and were voted on by a group of specialists. NList_dot_numeric2(2Digit)=SubBList1(2Digit)=NList_dot_numeric(2Digit)=SubBList1(2Digit) Results: The certainty of evidence was generally rated as very low. Therefore, 16 of 17 recommenda- NList_dot_numeric3(2Digit)=SubBList1(2Digit)=NList_dot_numeric(2Digit)=SubBList1(2Digit) tions are conditional. In patients with chronic diarrhea, consideration of risk factors (terminal ileal SubBList3(2Digit)=HeadD=SubBList(2Digit)=HeadD resection, cholecystectomy or abdominal radiotherapy), but not additional symptoms, was recom- SubBList2(2Digit)=HeadD=SubBList(2Digit)=HeadD mended for identification of patients with possible BAD. The group suggested testing using 75selenium SubBList2(2Digit)=HeadB=SubBList(2Digit)=HeadB homocholic acid taurine (where available) or 7α-hydroxy-4-cholesten-3-one, including patients with SubBList3(2Digit)=HeadB=SubBList(2Digit)=HeadB irritable bowel syndrome with diarrhea, functional diarrhea and Crohn’s disease without inflammation. Extract3=BList3=Extract1=BList3 Testing was suggested over empiric bile acid sequestrant therapy (BAST). Once remediable causes are BList3=Extract3=BList3=Extract3_0 managed, the group suggested cholestyramine as initial therapy, with alternate BAST when tolerability is an issue. The group suggested against BAST for patients with extensive ileal Crohn’s disease or resec- tion and suggested alternative antidiarrheal agents if BAST is not tolerated. Maintenance BAST should be given at the lowest effective dose, with a trial of intermittent, on-demand administration, concurrent medication review and reinvestigation for patients whose symptoms persist despite BAST. Conclusions: Based on a systematic review, BAD should be considered for patients with chronic diar- rhea. For patients with positive results from tests for BAD, a trial of BAST, initially with cholestyramine, is suggested. Keywords: C4; Fibroblast growth factor 19; FGF19; IBS; SeHCAT © 2019 by the Canadian Association of Gastroenterology and the AGA Institute This article is being published jointly inJournal of the Canadian Association of Gastroenterology and Clinical Gastroenterology and Hepatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// e10 creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Journal of the Canadian Association of Gastroenterology, 2020, Vol. 3, No. 1 e11 Diarrhea is a common symptom in the general population of have been guidelines on the management of chronic diarrhea from developed countries. Among community-dwelling persons the the American Gastroenterological Association (9), and the British 1-month rate of diarrhea was 7.6% in Canada and the United Society of Gastroenterology (10), but diagnosis and management States, 6.4% in Australia and 3.4% in Ireland; approximately of BAD was not assessed extensively in these publications. The 20% of subjects sought medical care for this symptom (1). British Society of Gastroenterology updated guidelines on the in- The prevalence of chronic diarrhea has been estimated to affect vestigation of chronic diarrhea in adults (11), published after the approximately 5% of this population overall (2), and may be consensus meeting, addressed some issues related to BAD. higher among older individuals (3). The purpose of this guideline is to critically review the litera- The most common causes of chronic diarrhea in clinical ture relating to diagnostic testing, and the induction and main- practice are functional disorders (e.g., irritable bowel syn- tenance treatment of BAD, with the aim of developing specific drome [IBS]), and inflammatory diseases (e.g., Crohn’s dis- consensus recommendations for patients with BAD. Downloaded from https://academic.oup.com/jcag/article-abstract/3/1/e10/5661094 by guest on 26 March 2020 ease, celiac disease) (3). However, a common but frequently underdiagnosed cause of chronic diarrhea is dysregulated bile Methods acid recycling within the enterohepatic circulation: either ex- cessive biosynthesis/secretion of bile acids, or malabsorption Scope and Purpose of bile acids by the ileum. Unabsorbed bile acids in the colon These consensus statements focused on specific issues pertaining appear to cause diarrhea by stimulating fluid, mucus, or sodium to the medical management of BAD, which the participants and secretion; increasing gastrointestinal motility; damaging the GRADE experts (F.T., G.I.L.) identified a priori. mucosa or stimulating defecation (3,4). Three subtypes of bile acid diarrhea (BAD) have been Sources, Literature Searches and Systematic Reviews described: type 1, patients with terminal ileal disease (e.g., The Editorial Office of the Cochrane Upper Gastrointestinal and Crohn’s disease, resection) or radiation injury resulting in im- Pancreatic Diseases Group at McMaster University performed paired reabsorption of bile acids; type 2, idiopathic or primary; a systematic search of Medline, Embase, and the Cochrane and type 3, other conditions (e.g., celiac disease, cholecystec- Central Register of Controlled Trials for literature published tomy) that alter intestinal motility or bile acid absorption (3,5). between 1990 and September 2017. Key search terms were as BAD has been reported in approximately 25% to 35% of patients follows: bile acid, cholecystectomy, cholestyramine, colestipol, with chronic diarrhea or diarrhea-predominant IBS (IBS-D) colesevelam, diarrhea, loperamide, malabsorption, resection, (6). Rates are even higher in patients with underlying terminal SeHCAT and sequestrants. An additional search of the databases ileal disease, or other conditions such as cholecystectomy. for SeHCAT trials published before 1990 (database inception as The diagnosis of BAD continues to be a challenge, although start date) also was performed. Only human studies published in this may be improved in the future with the general availa- English were considered. Further details of the search strategies bility of screening serologic tests and other diagnostic tests are provided in Supplementary Appendix 1. (discussed later).
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