Letter: hydroxypropyl cellulose as therapy for chronic diarrhoea in patients with bile acid malabsorption – possible mechanisms

Brydon, W. G.; Walters, Julian R.F.; Ghosh, Subrata; Culbert, Pearl

doi:10.1111/apt.13678

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…63 Although HPC was chosen as a placebo, it may be pharmacologically active, and a small case series suggested it may be effective in BAD. 63,64 The RCT was an 8-week study in 26 patients with chronic functional watery diarrhea or IBS-D, of which 77% of the cholestyramine-treated and 54% of HPC-treated patients had a SeHCAT retention rate of 10% or less. 63 There was no significant difference in clinical remission rates (defined as <3 bowel movements/d over 1 week, with <1 watery stool/d) between treatments (53.8% vs 38.4%; P ¼ .43).…”

Section: Gradementioning

confidence: 99%

“…However, there was a significant improvement in the decrease in watery stools per day (-92.4% AE 3.5% vs -75.8% AE 7.1%; P ¼ .048). Because HPC binds bile acids and may have a bulking effect, it may have some efficacy for BAD [63][64][65][66] ; this makes it difficult to interpret the lack of significant differences in clinical remission rates with HPC compared with cholestyramine.…”

Section: Gradementioning

confidence: 99%

“…HPC may improve diarrhea in patients with BAD through its bulking effects and its ability to bind bile acids. [63][64][65][66] In addition, some patients may benefit from loperamide; given its low cost and relatively good safety profile (although no cost-effectiveness data are available), a treatment trial may be warranted. Discussion.…”

Section: Maintenance Therapy For Bile Acid Diarrheamentioning

confidence: 99%

See 2 more Smart Citations

Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea

Sadowski

Camilleri

Chey

et al. 2020

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS: Chronic diarrhea affects about 5% of the population overall. Altered bile acid metabolism is a common but frequently undiagnosed cause. METHODS: We performed a systematic search of publication databases for studies of assessment and management of bile acid diarrhea (BAD). The certainty (quality) of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Patient population, intervention, comparator, and outcome questions were developed through an iterative process and were voted on by a group of specialists. RESULTS: The certainty of evidence was generally rated as very low. Therefore, 16 of 17 recommendations are conditional. In patients with chronic diarrhea, consideration of risk factors (terminal ileal resection, cholecystectomy, or abdominal radiotherapy), but not additional symptoms, was recommended for identification of patients with possible BAD. The group suggested testing using 75 selenium homocholic acid taurine (where available) or 7a-hydroxy-4-cholesten-3-one, including patients with irritable bowel syndrome with diarrhea, functional diarrhea, and Crohn's disease without inflammation. Testing was suggested over empiric bile acid sequestrant therapy (BAST). Once remediable causes are 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 resection 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 diarrhea. For patients with positive results from tests for BAD, a trial of BAST, initially with cholestyramine, is suggested.

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Section: Gradementioning

confidence: 99%

Section: Gradementioning

confidence: 99%

Section: Maintenance Therapy For Bile Acid Diarrheamentioning

confidence: 99%

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Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea

Sadowski

Camilleri

Chey

et al. 2020

Clinical Gastroenterology and Hepatology

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“…HPC has previously been shown to adsorb bile acids, suggesting a possible mechanism for this effect (256,302,386). Interestingly, HPC does not appear to increase serum C4, indicating that it may allow for some retention of bile acid signaling while also limiting their effect on colonic secretion (53).…”

Section: Treatment Of Badmentioning

confidence: 95%

Intestinal Absorption of Bile Acids in Health and Disease

Ticho

Malhotra

Dudeja

et al. 2019

Comprehensive Physiology

147

108

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The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Extensive research has focused on delineating the processes of bile acid absorption and determining the contribution of dysregulated ileal signaling in the development of intestinal and hepatic disorders. For example, a decrease in the levels of the bile acid-induced ileal hormone FGF15/19 is implicated in bile acidinduced diarrhea (BAD). Conversely, the increase in bile acid absorption with subsequent overload of bile acids could be involved in the pathophysiology of liver and metabolic disorders such as fatty liver diseases and type 2 diabetes mellitus. This review article will attempt to provide a comprehensive overview of the mechanisms involved in the intestinal handling of bile acids, the pathological implications of disrupted intestinal bile acid homeostasis, and the potential therapeutic targets for the treatment of bile acid-related disorders.

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“…In comparison, the placebo hydroxypropyl cellulose group showed response rates of 25% and 38.5% respectively (no statistical difference between the two treatments) [26]. However, there was a statistically significant difference in the decreased number of watery stools with cholestyramine compared to hydroxypropyl cellulose, which also binds bile salts in the colon without affecting hepatic BA synthesis [27]. Eleven percent of the cholestyramine group had to discontinue treatment because of side effects and unpalatability [28].…”

Section: Treatments For Bile Acid Diarrheamentioning

confidence: 99%

Bile acid disease

Oduyebo

Camilleri²

2017

Current Opinion in Gastroenterology

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Purpose of Review Our objective was to review advances in bile acids (BA) in health and disease published in the last two years. BA diarrhea (BAD) is recognized as a common cause of chronic diarrhea, and its recognition has been facilitated by development of new screening tests. Recent Findings Primary BAD can account for 30% of cases of chronic diarrhea. The mechanisms leading to BAD include inadequate feedback regulation by fibroblast growth factor 19 (FGF-19) from ileal enterocytes, abnormalities in synthesis or degradation of proteins involved in FGF-19 regulation in hepatocytes, and variations in function of the bile acid receptor, TGR5 (GPBAR1). 75SeHCAT is the most widely used test for diagnosis of BAD. There has been significant validation of fasting serum FGF-19 and 7 α-hydroxy-cholesten-3-one (C4), a surrogate measure of BA synthesis. BA sequestrants are the primary treatments for BAD; the FXR-FGF-19 pathway provides alternative therapeutic targets for BAD. BA-stimulated intestinal mechanisms contribute to the beneficial effects of bariatric surgery on obesity, glycemic control, and the treatment of recurrent C. difficile infection. Summary Renewed interest in the role of BAs is leading to novel management of diverse diseases besides BAD.

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Letter: hydroxypropyl cellulose as therapy for chronic diarrhoea in patients with bile acid malabsorption – possible mechanisms

Cited by 6 publications

References 7 publications

Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea

Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea

Intestinal Absorption of Bile Acids in Health and Disease

Bile acid disease

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