Prevalence of biliary acid malabsorption in patients with chronic diarrhoea of functional characteristics: a prospective study, Flores et al, 2021

[Andy]

Background
Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis.

Methods
This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea

Results
38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine.

Conclusions
Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea.

Open access, https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01637-4

 

[Hutan]

BAM! to ideas of functional illness (Bile Acid Malabsorption, that is.)

In this prospective study carried out in a tertiary hospital in Spain, we show that more than 50% of consecutive patients referred for chronic diarrhoea of unknown origin and with functional characteristics were diagnosed with type 2 BAD by means of 75SeHCAT test. The results presented herein confirm previous data showing that the prevalence of type 2 BAD is high among patients referred for chronic diarrhoea with functional characteristics

BAD (Bile Acid Diarrhoea)

Bile acid malabsorption (BAM) is a well recognised—but often forgotten [6]—pathophysiological event in patients with chronic diarrhoea; indeed, up to a third of patients previously labelled with an IBS-D or FD actually suffer from bile acid diarrhoea (BAD)....
Increased [bile acids] entering the colon stimulate water and chloride secretion, inhibit water and sodium absorption and increase colonic motility through several mechanisms revised elsewhere

Seems like the detailed physiology is fairly well understood:

Type 2 BAD is estimated to occur in 28.1% of patients diagnosed with IBS-D [7], and seems to be the result of an impaired inhibition of BA synthesis due to a decreased levels of fibroblast growth factor 19 (FGF-19) [10]. FGF-19 is an enteroendocrine hormone synthesized in the terminal ileum in response to the stimulation by BA of the nuclear farnesoid X receptor (FXR), expressed by intestinal epithelial cells [11]. Under physiological conditions, FGF-19 is released into the portal circulation and interacts with the FGF receptor 4 on the hepatocytes, decreasing the synthesis of new BA; it also reduces the uptake of BA from the enterocyte, reducing the expression of their transporters

Of course, every participant who didn't qualify for the Type 2 BAD diagnosis was left in the functional illness bucket.

The diagnosis of functional disorder (FD or IBS-D) was made, based on the Rome IV criteria of functional digestive diseases, when the 75SeHCAT test was negative.

Cos, well, now that we know about bile acid diarrhoea, of course we know all that there is to know about possible causes of diarrhoea...


And this one is important - doing the test early rather than slapping a functional diagnosis on someone is thought likely to reduce subsequent healthcare related costs, not to mention opening up treatment possibilities:

And third, it has been recently demonstrated that early BAM diagnosis by means of 75SeHCAT test reduces subsequent investigations [26] and healthcare-related costs

 

[Hutan]

Here's a 2020 BMJ paper on this:
https://fg.bmj.com/content/early/2020/09/22/flgastro-2020-101436
Bile acid diarrhoea: pathophysiology, diagnosis and management

The actual incidence of bile acid diarrhoea (BAD) is unknown, however, there is increasing evidence that it is misdiagnosed in up to 30% with diarrhoea-predominant patients with irritable bowel syndrome. Besides this, it may also occur following cholecystectomy, infectious diarrhoea and pelvic chemoradiotherapy.

This phenomenon was first described in 1967

The BSG guidelines state that patients with chronic diarrhoea should all be investigated to exclude BAD either with a 75SeHCAT scan where available or C4 given current evidence base.42 75SeHCAT (Selenium-75 homocholic acid taurine test), first described in 1982, is used to determine the amount of bile acids retained after 7 days.43 44 The National Institute for Health and Care Excellence diagnostic guidance report on 75SeHCAT in 2012 stated that given the prevalence of undiagnosed BAD, there is potential for patient and system benefits associated with 75SeHCAT investigations.45 The report also suggested that insufficient evidence exists to determine its cost-effectiveness and recommended further research to evaluate this technology and effects of treatment46 Its 2016 review, made no changes in light of lack of new evidence on 75SeHCATs comparative diagnostic accuracy and.2020 review is awaited.

A systematic review and meta-analysis comprising 36 studies and 5028 patients on BAD biomarkers concluded that 75SeHCAT had a highest diagnostic yield to date (limited by study heterogeneity) with 25% previously diagnosed as having functional bowel disorders actually had primary BAD.47

BAD is a treatable disease, however, the delay in diagnosis causes a significant increase in the diagnostic care cost as well as affecting the quality of life of patients.

 

[Sean]

BAD is a treatable disease, however, the delay in diagnosis causes a significant increase in the diagnostic care cost as well as affecting the quality of life of patients.​

Also true for currently untreatable diseases. Early diagnosis and generic management alone are highly desirable goals, even in the absence of treatments. Just knowing what the problem lets patients maximise what choices they do have.

Very good to see this message getting into the peer-review literature. Anything that delays diagnosis and treatment/management will increase morbidity and (where applicable) mortality rates.