Selenium Homocholic Acid Taurine Research Articles

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

Simple SummaryBile acid malabsorption is a common albeit a very underdiagnosed gastroenterology condition especially in cancer cohort of patients. Our study, performed at the National leading centre for treatment of cancer, focuses on prevalence and management of bile acid malabsorption in patients reviewed in our specialized clinic. Currently, precise diagnosis and excellent treatments exist for this disease.The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019–January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/− 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective.

Primary bile acid diarrhea in a community gastroenterology practice

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 ofthem 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.

A positive SeHCAT test results in fewer subsequent investigations in patients with chronic diarrhoea

Chronic diarrhoea is a common condition, resulting from a number of different disorders. Bile acid diarrhoea, occurring in about a third of these patients, is often undiagnosed. We hypothesised that...

A UHPLC–MS/MS method for the quantification of 7α-hydroxy-4-cholesten-3-one to assist in diagnosis of bile acid malabsorption

Bile acids malabsorption (BAM) is encountered in numerous gastrointestinal pathologies and is a good example of a treatable cause of watery diarrhea after ileal resection. The gold standard for diagnosing BAM is the selenium homocholic acid taurine test (SeHCAT), an expensive and complex analysis. An alternative method is the quantification of 7α-hydroxy-4-cholesten-3-one (C4). Here, we present a simple, ultra high-performance liquid chromatography–tandem mass spectrometry method to measure C4 in human serum. To avoid time consuming sample preparation (e.g., derivatization, solid phase extraction), we used absorption chemistry-based extraction plates. This method demonstrates a lower limit of quantification of 5ng/mL and is linear over a concentration range from 5 to 300ng/mL (R2=0.9977). Inaccuracy and imprecision were less than 15%. The validated method is currently used for routine measurement of C4 from serum in patients to confirm BAM diagnosis.

How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes

ObjectivesBile acid diarrhoea (BAD) is an underdiagnosed condition producing diarrhoea, urgency and fear of faecal incontinence. How patients experience these symptoms has not previously been studied. Bile Acid Malabsorption (BAM)...

Management of bile acid malabsorption using low-fat dietary interventions: a useful strategy applicable to some patients with diarrhoea-predominant irritable bowel syndrome?

This study evaluates the efficacy of low-fat dietary interventions in the management of gastrointestinal (GI) symptoms due to bile acid malabsorption. In total, 40 patients with GI symptoms and a 7-day (75)selenium homocholic acid taurine (SeHCAT) scan result of <20%, were prospectively recruited and then advised regarding a low-fat dietary intervention. Before and after dietary intervention, patients rated their GI symptoms using a 10-point numerical scale, and recorded their intake in 7-day dietary diaries. After dietary intervention, the median scores for all GI symptoms decreased, with a significant reduction for urgency, bloating, lack of control, bowel frequency (p ≥: 0.01). Mean dietary fat intake reduced to 42 g fat after intervention (p ≥: 0.01). Low-fat dietary interventions in patients with a SeHCAT scan result of <20% leads to clinically important improvement in GI symptoms and should be widely used.

High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients With Diarrhea-Predominant Irritable Bowel Syndrome Based on Rome III Criteria

Some studies have found that patients with idiopathic bile acid diarrhea (BAD) present with symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS). However, these studies either were retrospective, did not define D-IBS according to current criteria, or included patients with chronic functional diarrhea. We performed a prospective study of the prevalence of idiopathic BAD in consecutive patients fulfilling the Rome III criteria for D-IBS. We analyzed data from 118 consecutive adult patients who fulfilled the Rome III criteria for D-IBS (mean age, 41.7 y; 72.9% female), seen at 2 gastroenterology clinics in the United Kingdom. We excluded patients with risk factors for BAD (previous history of cholecystectomy, terminal ileal Crohn's disease, terminal ileal resection or right hemicolectomy, pelvic or abdominal radiotherapy, celiac disease, or microscopic colitis). Participants completed questionnaires at baseline (on demographics, hospital anxiety, somatization, and depression, as wellas the patient health questionnaire-12 and the Short Form-36), and then received the (75)selenium homocholic acid taurine retention test. Retention of (75)selenium homocholic acid taurine 7days after administration was used to identify patients with idiopathic BAD (mild BAD, 10%-14.9%; moderate BAD, 5.1%-9.9%; and severe BAD, ≤5%). Twenty-eight patients were found to have BAD (23.7% of total), with similar percentages at each study site (25.3% and 20%; P= .54). Eight patients had mild BAD (28.6%), 8 patients had moderate BAD (28.6%), and 12 patients had severe BAD (42.8%). There was no statistical difference in age, sex, depression, patient health questionnaire-12 responses, or SF-36 scores between individuals with vs without BAD. However, patients with BAD had a higher mean body mass index than patients without BAD (31.6 vs 26.4; P= .003). Physical activity (based on the Short Form-36) was significantly lower in subjects with moderate (43.8) or severe BAD (41.7), compared with patients with mild BAD (87.5) (P= .046). Almost 25% of patients presenting with D-IBS have idiopathic BAD; most cases are moderate to severe. Guidelines should advocate testing to exclude BAD before patients are diagnosed with D-IBS.

Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy

Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of patients who would otherwise be diagnosed with IBS. Studies of other approaches for diagnosis of BAD have shown increased bile acid synthesis, increased faecal levels of primary bile acids, dysbiosis and different urinary volatile organic compounds when compared with healthy controls or with other diseases. The role of the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical study has confirmed low FGF19 levels in BAD, and so a test to measure these levels could be developed for diagnosis. In animal models, FGF19 depletion by antibodies produces severe diarrhoea. Bile acids affect colonic function through farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the colon, FXR-dependent stimulation of ileal FGF19 production could be a logical mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in humans hold promise in providing novel treatments for this cause of chronic diarrhoea.

CLINICAL CHARACTERISTICS AND RISK FACTORS FOR BILE SALT MALABSORPTION

IntroductionBile acid malabsorbtion (BAM) is a known cause of chronic diarrhoea. The condition is easily diagnosed by performing a selenium homocholic acid taurine (SeHCAT) test, with 7-day retention of <10%...

Evaluation of Fibroblast Growth Factor 19 in the Diagnosis of Bile Acid Diarrhea

Introduction The prevalence of bile acid diarrhoea (BAD) is estimated to be 1%, but the condition remains under diagnosed, partly because the selenium homocholic acid taurine (SeHCAT) test is not widely available. Fibroblast Growth Factor 19 (FGF19) produced in the terminal ileum in response to bile acid absorption plays an important role as a negative regulator of bile acid synthesis and low median FGF19 levels were shown in patients with primary BAD. The aim of this study was to evaluate the relationship between fasting FGF19 levels and SeHCAT in a large prospective group of patients defined by SeHCAT results. We also compared FGF19 levels at the time of colonoscopy in order to assess the effect of bowel preparation. Methods Patients recruited with chronic diarrhoea had SeHCAT testing as part of routine workup and provided fasting blood samples. Group 1 (n=74) were diagnosed as having BAD with a SeHCAT value of less than 15% and included patients with any of the possible causes of BAD. Group 2 patients (n=63) had SeHCAT values of greater than 15%. Serum FGF19 was measured in all patients by ELISA. Data were analysed to compare the relationship between FGF19 and SeHCAT in both groups. 17 patients had additional blood samples taken before colonoscopy after a standard bowel prep. Results FGF19 and SeHCAT were positively related (r=-0.49 Spearman rank correlation). The median FGF19 values in Group 1 and Group 2 were 146 pg/ml and 242 pg/ml respectively (p Conclusion The use of SeHCAT to diagnose BAD is currently the gold standard test of choice, but has its limitations. In this large prospective group we have shown a positive correlation between SeHCAT and FGF19. Potentially FGF19, which is a simple blood test, could be utilised as an alternative diagnostic or screening test for this condition. Further development and refinement to account for factors such as obesity, timing of a sample, and the effect of bowel preparation for colonoscopy may improve the sensitivity and specificity of the test.

Bile acid malabsorption: An under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms

Objective. Bile acid malabsorption (BAM) has been reported as a possible cause of diarrhea predominant irritable bowel syndrome (D-IBS) type symptoms. We aimed to determine how commonly patients with D-IBS type symptoms had a diagnosis of BAM as demonstrated by a positive SeHCAT (75 Selenium-homocholic acid taurine) test (retention <10% at seven days). Materials and methods. A retrospective analysis was undertaken of patient's records for all patients who underwent a SeHCAT test between 2001 and 2009 in a tertiary hospital (Group A). Concurrently, a cohort of patients with Rome II D-IBS type symptoms was examined to determine the potential utility of SeHCAT test (Group B). Results. In Group A 39.2% (n = 107/273) of patients had a positive SeHCAT result. The median time from first hospital visit to SeHCAT result was 30 weeks. Predictive factors for BAM: terminal ileal Crohn's disease (p < 0.01), terminal ileal resection (p < 0.01), and previous cholecystectomy (p < 0.01). 33.6% of patients who had a positive SeHCAT also had Rome II D-IBS. In Group B the D-IBS control cohort only 1.9% of patients had undergone a SeHCAT scan (p < 0.001 compared to Group A). Conclusion. BAM is common and should be considered earlier when investigating unselected patients with D-IBS type symptoms.

* Evaluation of fibroblast growth factor 19 in the diagnosis of bile acid diarrhoea

IntroductionThe prevalence of bile acid diarrhoea (BAD) is estimated to be 1%, but the condition remains under diagnosed, partly because the selenium homocholic acid taurine (SeHCAT) test is not widely...

Postinfective bile acid malabsorption

Postinfective bile acid malabsorption comprises a group of patients with a history of an episode of acute gastroenteritis triggering chronic diarrhoea. We identified these patients retrospectively from our medical records and assessed their long-term clinical course. We examined the records of 135 patients with 75 selenium-homocholic acid taurine results less than 10% (1 week retention). Twenty-five patients (13 female, 12 male) had a diagnosis of postinfective bile acid malabsorption established after extensive investigations. Cholestyramine was used to treat diarrhoea with a mean frequency of diarrhoea decreasing from 7.8 to 1.9 (P=0.001). The mean cholestyramine dose decreased from 8.2 to 5.4 g/day (P=0.005). Eighteen of 25 (72%) patients had a successful resolution of their diarrhoea by cholestyramine and have continued it to date. The median duration of outpatient follow-up was 1.58 years (range: 1-5 years). A further prospective telephone enquiry of these 18 patients revealed that 15 of 18 patients continued to take cholestyramine (median: 6 years, range: 1-15 years). There were no hospital admissions related to diarrhoea and there was no mortality in this group of patients. The long-term outlook of this group of patients is excellent. We have shown the chronic nature of this condition as evidenced by the continued requirement of cholestyramine.

PP-020 A prospective study of fibroblast growth factor 19 in patients with chronic diarrhoea and possible bile acid malabsorption

Introduction Chronic diarrhoea resulting from excess bile acids in the colon (“bile acid malabsorption”, BAM) is usually diagnosed by the selenium homocholic acid taurine (SeHCAT) test and responds to bile acid sequestrants. Other tests for BAM including serum levels of 7α-hydroxy-4-cholesten-3-one are not widely available. Our group suggested that disordered negative feedback inhibition by Fibroblast Growth Factor 19 (FGF19), produced by the ileum, of hepatic bile acid synthesis results in an excess of bile acids entering the colon, causing bile acid diarrhoea. We aim to examine further the role of FGF19 in a larger group of patients with chronic diarrhoea. Methods 62 patients have been prospectively recruited with chronic diarrhoea. All patients had routine investigations for chronic diarrhoea to exclude other causes and all had SeHCAT tests. Three different patient groups were defined according to the diagnosis based on SeHCAT results: SeHCAT 15% (n=28). All patient demographics and symptoms were recorded and fasting blood samples for FGF19 were collected and available in 54 patients. Serum FGF19 was quantified by ELISA using a commercially available kit. Results Fasting FGF19 levels were significantly lower in patients with primary and secondary BAM compared with the chronic diarrhoea group with normal SeHCAT results (medians 160 vs 139 vs 276 pg/ml, p Conclusion This study confirms that serum levels of an easily measurable hormone, FGF19, are significantly reduced in patients with bile acid diarrhoea, and are not affected by chronic diarrhoea per se. These patients also have a higher BMI. Other symptoms such as faecal incontinence, urgency abdominal pain, bloating and steatorrhoea are also common findings in these patients. These results provide further evidence that there is a disruption of a homeostatic mechanism in the control of bile acid synthesis with an overproduction of bile acids leading to chronic watery diarrhoea.

Recent advances in the understanding of bile acid malabsorption

Bile acid malabsorption (BAM) is a syndrome of chronic watery diarrhoea with excess faecal bile acids. Disruption of the enterohepatic circulation of bile acids following surgical resection is a common cause of BAM. The condition is easily diagnosed by the selenium homocholic acid taurine (SeHCAT) test and responds to bile acid sequestrants. Idiopathic BAM (IBAM, primary bile acid diarrhoea) is the condition where no definitive cause for low SeHCAT retention can be identified. Review of PubMed and major journals. Evidence is accumulating that BAM is more prevalent than first thought. Management of chronic diarrhoea involves excluding secondary causes. Treatment of the condition is with bile acid binders. SeHCAT testing is not widely performed, limiting awareness of how common this condition can be. The underlying mechanism for IBAM has been unclear. Increasing awareness of the condition is important. Alternative mechanisms of IBAM have been suggested which involve an increased bile acid pool size and reduced negative feedback regulation of bile acid synthesis by FGF19. New sequestrants are available. Further research into the precise mechanism of IBAM is needed. Improvements in the recognition of the condition and optimization of treatment are required.

A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis

Primary (idiopathic) bile acid malabsorption (BAM) is a common, yet underrecognized, chronic diarrheal syndrome. Diagnosis is difficult without selenium homocholic acid taurine (SeHCAT) testing. The diarrhea results from excess colonic bile acids, but the pathogenesis is unclear. Fibroblast growth factor 19 (FGF19), produced in the ileum in response to bile acid absorption, regulates hepatic bile acid synthesis. We proposed that FGF19 is involved in bile acid diarrhea and measured its levels in patients with BAM. Blood was collected from fasting patients with chronic diarrhea; BAM was diagnosed by SeHCAT. Serum FGF19 was measured by enzyme-linked immunosorbent assay. Serum 7alpha-hydroxy-4-cholesten-3-one (C4) was determined using high-performance liquid chromatography, to quantify bile acid synthesis. Data were compared between patients and subjects without diarrhea (controls). Samples were taken repeatedly after meals from several subjects. The median C4 level was significantly higher in patients with primary BAM than in controls (51 vs 18 ng/mL; P < .0001). The median FGF19 level was significantly lower in patients with BAM (120 vs 231 pg/mL; P < .0005). There was a significant inverse relationship between FGF19 and C4 levels (P < .0004). Low levels of FGF19 were also found in patients with postcholecystectomy and secondary bile acid diarrhea. Abnormal patterns of FGF19 levels were observed throughout the day in some patients with primary BAM. Patients with BAM have reduced serum FGF19 which may be useful in diagnosis. We propose a mechanism whereby impaired FGF19 feedback inhibition causes excessive bile acid synthesis that exceeds the normal capacity for ileal reabsorption, producing bile acid diarrhea.