SeHCAT Test Research Articles

The Pathophysiology of Bile Acid Diarrhoea: Differences in the Colonic Microbiome, Metabolome and Bile Acids

Background: Bile acid diarrhoea (BAD) is common, often unrecognised, or thought to be irritable bowel syndrome with diarrhoea (IBS-D). It results from increased loss of bile acids (BAs) into the colon but mechanisms are unclear. The gut microbiota plays key roles in the metabolism of primary BAs to form secondary BAs, which have differing impacts on intestinal metabolism and homeostasis. The aim of this study was to profile the gut microbiome in BAD and to investigate the differences in bacterial metabolic products and specific bile acids. Methods: Patients with BAD diagnosed by SeHCAT testing, were compared with other IBS-D patients, and healthy controls. Faecal 16S ribosomal RNA gene analysis was undertaken. Faecal short chain fatty acid (SCFA) and urinary fermentation metabolite profiles (volatile organic compounds; VOCs) were measured. BAs were quantified in serum and faeces. Findings: Faecal bacterial diversity was significantly reduced in patients with BAD, but several taxa were enriched compared to IBS-D. SCFA amounts differed in BAD, controls and IBS-D, with significantly more propionate in BAD. Separation of VOC profiles was evident between all groups with the greatest discrimination between IBS-D and controls. Unconjugated and primary BA in serum and faeces were significantly higher in BAD. The proportion of faecal primary BA was inversely related to SeHCAT values. Interpretation: BAD results in dysbiosis, with differences in metabolites including VOC, SCFA and higher concentrations of primary BAs when compared to IBS-D. These findings provide new mechanistic insights into the pathophysiology of BAD. Funding Statement: Funding was from UHCW Trust’s charity as well as the Midlands Gastroenterology Society and Bardhan Research and Education Trust (BRET). Declaration of Interests: JW has been a consultant for, and reports institutional grant funding from GE Healthcare, and Prometheus diagnostics. RA has delivered educational talks for GE Healthcare. No disclosures are made by all authors Ethics Approval Statement: Scientific and ethical approval was acquired from the local Research and Development Office as well as Warwickshire Ethical committee ref: 09/H1211/38. Written informed consent was obtained from all participants in the study.

Mo1542 – Primary Bile Acids in a Single Fecal Sample for the Diagnosis of Bile Acid Diarrhea: Relationship to Sehcat Testing

Mo1542 – Primary Bile Acids in a Single Fecal Sample for the Diagnosis of Bile Acid Diarrhea: Relationship to Sehcat Testing

Systematic review with meta-analysis: the prevalence of bile acid malabsorption and response to colestyramine in patients with chronic watery diarrhoea and previous cholecystectomy.

A limited number of small-sized studies suggest that bile acid diarrhoea is frequent in patients with chronic watery diarrhoea and previous cholecystectomy. To perform a systematic review and meta-analysis to assess the prevalence of bile acid diarrhoea in patients with chronic watery diarrhoea and previous cholecystectomy, and their response to colestyramine, including a new consecutive series of patients. MEDLINE and EMBASE were searched up to January 2018. Selected studies included patients with previous cholecystectomy and chronic watery diarrhoea assessed by the 23-seleno-25-homotaurocholic acid (SeHCAT) test. We calculated the pooled rate of bile acid diarrhoea using the inverse double arcsine square root method. Additionally, the medical records of 291 consecutive patients with chronic watery diarrhoea in whom a SeHCAT test was performed were retrospectively reviewed and 74 with previous cholecystectomy were included in the meta-analysis. The search strategy identified eight relevant studies, which, together with the data of the present series, comprise 361 individuals. The pooled bile acid diarrhoea rate was 70% (95% CI 56%-82%), and was similar when using cut-offs of 10% or 15%. There was substantial heterogeneity (I2 =84%). Five studies comprising 166 patients evaluated the effect of colestyramine in patients with bile acid diarrhoea. The pooled colestyramine response rate was 79% (95% CI 63%-91%) with substantial heterogeneity (I2 =73%). Two-thirds of patients with chronic watery diarrhoea and previous cholecystectomy have bile acid diarrhoea. Response to colestyramine in these patients is good.

Pros and Cons of the SeHCAT Test in Bile Acid Diarrhea: A More Appropriate Use of an Old Nuclear Medicine Technique.

Bile acid malabsorption (BAM) causing chronic diarrhea may be due to organic as well as functional disorders, and some of them were included under the general label of diarrheic-type irritable bowel syndrome (IBS-D). The 75-selenium homocholic acid taurine (SeHCAT) test is a nuclear medicine investigation considered to be the gold standard for the diagnosis of bile acid malabsorption (BAM). Many studies demonstrate that it could be effective in the clinical workout of chronic diarrhea due to different conditions. The SeHCAT test provides a quantitative assessment to estimate the severity of BAM and the possible response to therapy with bile acid sequestrants (BASs). However, there is no general agreement regarding its cutoff value and the test is not widely available. The aim of this review is to discuss the advantages and disadvantages of the SeHCAT test in clinical practice.

Incidence and predictive factors for positive 75SeHCAT test: improving the diagnosis of bile acid diarrhoea

Aims: To determine the value of 75SeHCAT retention in determining bile acid diarrhoea (BAD), treatment response and predictors of a positive result.Methods: Retrospective casenote review of consecutive patients undergoing 75SeHCAT from 2008 to 2014, including gender, age, history, clinical, and laboratory parameters. This included diseases associated with Type 1 BAD (ileal resection, Crohn’s disease) and Type 3 BAD. Chi-squared test and logistic regression determined factors predictive of BAD. Subjective response to treatment with bile acid sequestrants (BAS) was analysed with respect to the 75SeHCAT result.Results: Of 387 patients, 154 (39.7%) were male and average age was 50 years. Ninety-five patients (24.5%) were investigated for Type 1 BAD, 86 (22.2%) for Type 3, and 206 patients (53.2%) for Type 2 or idiopathic BAD. There was a large increase in the number performed with time but no difference in percentage positive tests. One hundred and seventy-nine patients (46.2%) had BAD. Positive result was commonest in possible Type 1 and they had most severe BAD. Ninety-nine patients had severe BAD (<5% 75SeHCAT retention), 47 moderate BAD (5% to <10% retention), and 33 mild BAD (10% to <15% retention). Predictors of a positive 75SeHCAT were right hemicolectomy (OR 4.88), cholecystectomy (OR 2.44), and Crohn’s (OR 1.86). A positive 75SeHCAT predicted a good or partial response to BAS of 66.7% (mild), 78.6% (moderate), or 75.9% (severe BAD).Conclusion: 75SeHCAT test use increased in 2008–2014, with high positive results throughout. Ileal resection, Crohn’s, and cholecystectomy independently predict BAD. 75SeHCAT predicted response to BAS.

PTH-087 Severity of Bile Acid Malabsorption Does Not Correlate with Length of Ileal Resection or Response to Bile Salt Sequestrant Therapy in Crohn’s Disease

Introduction Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn’s disease (CD) patients with ileal resection and can lead to complications such as renal and biliary stone disease. BAM is usually diagnosed by selenium labelled homo-taurocholic acid test (75 SeHCAT) but its availability is limited. Thus, large proportions of resected CD patients either remain undiagnosed or subject to empirical therapy. There is a paucity of studies examining the correlation between length of ileal resection and severity of BAM which will be of particular use to clinicians with no recourse to diagnostic testing for BAM. Methods We identified all CD patients with a prior surgical resection who underwent 75 SeHCAT testing at our institute. Testing was based on the treating clinician’s discretion. The length of resected ileum was recorded from histopathology report. Correlation between length of resected ileum and percentage retention on 75 SeHCAT was assessed using a Spearman’s correlation test. Response to treatment with bile salt sequestrant and 75 SeHCAT retention values (using a cut point of 5%) was analysed using Fisher’s exact test. Results A total of 40 patients were identified with a mean age of 45 (SD±13), of which 6 (15%) were men. The median length of resected ileum was 22.8 cms (range 5.8–61.0 cms) with a median of 1 resection (range 1–4). Overall, 38 patients (95%) had 75 SeHCAT retention values of 5% and the remaining 18 (86%) had values Conclusion There was no correlation between length of ileal resection and severity of BAM as defined by 75 SeHCAT retention values. Response to bile salt sequestrant therapy was not dependent on 75 SeHCAT retention values though overall clinical response was good. Disclosure of Interest K. Lo: None Declared, H. Riyat: None Declared, Y. Prasad: None Declared, S. Subramanian Speaker bureau with: MSD, Abbvie, Shire, Ferring, Actavis, Conflict with: Advisory board Boehringer-Ingelheim, Vifor pharma, MSD, Abbvie, Shire

Review article: bile acid diarrhoea - pathogenesis, diagnosis and management.

Bile acid diarrhoea results from imbalances in the homoeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease/dysfunction, associated with other GI pathology or can be idiopathic. To summarise the different types of bile acid diarrhoea and discuss the currently available diagnostic methods and treatments. Bile acid diarrhoea is found in up to 40% of patients diagnosed as having functional diarrhoea/IBS-D, and in up to 80% of patients who have undergone ileal resection. It is likely under-diagnosed and under-treated. In idiopathic disease, errors in regulation feedback of fibroblast growth factor 19 contribute to the development of the condition. Clinical therapeutic trials for bile acid diarrhoea have been used to diagnose it, but the 75 SeHCAT test is the primary current method. It is sensitive, specific and widely available, though not in the USA. Other diagnostic methods (such as serum measurement of the bile acid intermediate 7α-hydroxy-4-cholesten-3-one, or C4) have less widespread availability and documentation, and some (such as faecal measurement of bile acids) are significantly more complex and costly. First-line treatment of bile acid diarrhoea is with the bile acid sequestrant cholestyramine, which can be difficult to administer and dose due to gastrointestinal side effects. These side effects are less prominent in newer agents such as colesevelam, which may provide higher efficacy, tolerability and compliance. Bile acid diarrhoea is common, and likely under-diagnosed. Bile acid diarrhoea should be considered relatively early in the differential diagnosis of chronic diarrhoea.

A Multicenter Prospective Study to Investigate the Diagnostic Accuracy of the SeHCAT Test in Measuring Bile Acid Malabsorption: Research Protocol.

BackgroundBile acid malabsorption (BAM) is one possible explanation for chronic diarrhea. BAM may be idiopathic, or result from ileal resection or inflammation including Crohn’s disease, or may be secondary to other conditions, including cholecystectomy, peptic ulcer surgery, and chronic pancreatitis. No “gold standard” exists for clinical diagnosis of BAM, but response to treatment with a bile acid sequestrant (BAS) is often accepted as confirmation. The SeHCAT (tauroselcholic [selenium-75] acid) test uses a radiolabeled synthetic bile acid and provides a diagnostic test for BAM, but its performance against “trial of treatment” is unknown. Fibroblast growth factor 19 (FGF-19) and 7-alpha-hydroxy-4-cholesten-3-one (C4) also offer potential new biomarkers of BAM.ObjectiveThis protocol describes a multicenter prospective study to evaluate the diagnostic accuracy of SeHCAT and 2 biomarkers in predicting BAM as assessed by trial of treatment.MethodsParticipating gastroenterology centers should have a minimum workload of 30 SeHCAT patients per annum. Patients should not be pregnant, on medication that could confound follow-up, or have any severe comorbidity. All eligible patients attending a gastrointestinal appointment will be invited to participate. On attending the SeHCAT test, blood and fecal samples will be collected for analysis of FGF-19 by enzyme-linked immunosorbent assay and for C4 and fractionated bile acids by liquid chromatography–mass spectrometry. A capsule containing radiolabeled SeHCAT will be administered orally and a scan performed to measure SeHCAT activity. Patients will return on day 7 to undergo a second scan to measure percentage SeHCAT retention. The test result will be concealed from clinicians and patients. BAS will be dispensed to all patients, with a follow-up gastroenterologist appointment at 2 weeks for clinical assessment of treatment response and adherence. Patients responding positively will continue treatment for a further 2 weeks and all patients will have a final follow-up at 8 weeks. The diagnostic accuracy of the SeHCAT test and biomarkers will be analyzed at different thresholds using sensitivity, specificity, positive and negative predictive value, likelihood ratios, and area under the curve in a sample of 600 patients. Multivariable logistic regression models will be used to assess the association between presence of BAM and continuous SeHCAT retention levels after adjustment for confounders.ResultsFunding is being sought to conduct this research.ConclusionsThe SeHCAT test for diagnosis of BAM has been in common use in the United Kingdom for more than 30 years and an evidence-based assessment of its accuracy is overdue. The proposed study has some challenges. Some forms of BAS treatment are unpleasant due to the texture and taste of the resin powder, which may negatively affect recruitment and treatment adherence. Trial of treatment is not as “golden” a standard as would be ideal, and itself warrants further study.

Are the definitions for chronic diarrhoea adequate? Evaluation of two different definitions in patients with chronic diarrhoea.

The classical definition of chronic diarrhoea is ≥3 defecations/day, with a stool weight of more than 200 g and duration of ≥4 weeks. However, with this definition many patients with substantial symptoms and pathology will be excluded from further investigations. As a consequence other definitions have been proposed, mainly based on evaluation of the stool form. To evaluate the accuracy of the classic criteria for diarrhoea in comparison with a definition based on stool consistency, using the Bristol Stool Form Scale. All patients were investigated with laboratory tests, upper and lower gastrointestinal endoscopy with biopsies, and SeHCAT test. They were asked to complete a diary recording stool frequency and consistency during a week, as well as other gastrointestinal symptoms (pain, bloating and gas). One hundred and thirty-nine subjects were eligible for analysis. Ninety-one had an organic cause of diarrhoea. Fifty-three patients had ≥3 loose stools/day, whereas 86 reported <3 stools/day. Ninety had a median stool consistency that was mushy or loose and 49 had harder stools. A higher proportion of subjects with an organic cause of their diarrhoea compared with subjects with a functional bowel disorder had ≥3 loose stools/day, 43/91 (47%) vs. 10/48 (21%) (p < 0.01). Similarly, more subjects with an organic cause of their diarrhoea versus patients with a functional bowel disorder had a median stool consistency that was mushy or watery, 73/91 (80%) vs. 17/48 (35%), p < 0.0001. When diarrhoea was defined according to stool form, more patients were classified correctly as having a functional disorder or organic disorder, compared with the classical definition (p < 0.05). Loose stools defined according to the Bristol Stool Form scale seem to be the best predictor of having an organic cause of the diarrhoea.

OC-036 Stimulated expression of ileal fibroblast growth factor 19 by bile acids is impaired in patients with primary and secondary bile acid diarrhoea

<h3>Introduction</h3> Bile acid diarrhoea (BAD) results from excess luminal bile acids (BA) in the colon. Most BAs are reabsorbed at the terminal ileum. Increased colonic BA occur secondary to ileal disease or resection (common in Crohn’s disease [CD]) leading to BA malabsorption and secondary BAD (SBAD). Primary BAD (PBAD) occurs in the absence of overt ileal disease or malabsorption. The peptide FGF19 is produced from enterocytes in response to BA absorption and maintains homeostasis of the BA pool size by inhibiting hepatic BA synthesis. Impaired ileal FGF19 production may underlie the excess faecal BA observed in PBAD and may be contributory in CD as a result of increased hepatic BA synthesis. We aimed to investigate whether BA-induced expression of FGF19 in the ileum is reduced in patients with PBAD or CD. <h3>Method</h3> Patients attending for colonoscopy (n = 58) were prospectively recruited and gave informed consent to give additional ileal biopsies. 14 patients had CD (4 with previous right hemi colectomy and 10 without), 16 patients had unexplained diarrhoea and had SeHCAT tests, and 28 controls. Groups of 2–3 biopsies (explants) were incubated separately for 6 h with either BA-free culture media (unstimulated controls), chenodeoxycholate (CDCA) or glyco-CDCA (GCDCA), both at 50 µM. After RNA extraction and cDNA synthesis, FGF19 expression was quantified relative to GAPDH by RT-PCR. <h3>Results</h3> In patients with unexplained diarrhoea SeHCAT 7d retention values were &lt;15% in 7 patients, indicating primary BAD, and &gt;15% in 9 who were normal diarrhoea controls. A positive correlation was found between SeHCAT retention and the magnitude of the fold change in FGF19 expression stimulated by either CDCA (r = 0.50, n = 16, p = 0.02) or by GCDCA (r = 0.76, n = 7, p = 0.02). The median CDCA stimulated fold change in FGF19 expression was significantly lower in CD compared to controls (87, n = 12 vs 251, n = 28, p = 0.03) and a similar non-significant trend was observed for median GCDCA stimulated expression (97, n = 10 vs 156, n = 13, p = 0.18). <h3>Conclusion</h3> Ileal explants from patients with lower SeHCAT 7d retention had a lower response to both CDCA and GCDCA. Patients with CD had lower responses to CDCA. As uptake of GCDCA is dependent on carrier-mediated apical BA uptake but CDCA is not, this implies abnormalities in the intracellular ileal FGF19 response to BA. A reduced capacity to induce ileal FGF19 expression in response to absorbed BA is proposed to increase faecal BA due to increased hepatic BA synthesis in primary BAD. In secondary BAD an impaired ileal BA FGF19 response may lead to an increase in BA synthesis and faecal BA that is disproportionate to the degree of ileal BA malabsorption. <h3>Disclosure of interest</h3> None Declared.

Sa1779 Soluble Plantain (Banana) Fibre Inhibits Epithelial Cell Damage in Response to Clostridium difficile and Its Toxins

G A A b st ra ct s fecal BA loss, which occurs in the absence of any absorptive defect within the terminal ileum, is due to increased BA synthesis, resulting from impaired FGF19 ileal production or hepatic actions. We aimed to investigate whether BA-induced expression of FGF19 in the ileum is reduced in patients with low SeHCAT retention.Methods: Patients being investigated for unexplained diarrhea (n=16) were prospectively recruited and gave informed consent at colonoscopy to give additional ileal biopsies. All had SeHCAT tests. Groups of 2-3 biopsies (explants) were incubated separately for 6h with either BA-free culture media (unstimulated controls), chenodeoxycholate (CDCA) or glyco-CDCA (GCDCA), both at 50uM. After RNA extraction and cDNA synthesis, FGF19 expression was quantified relative to GAPDH by RT-PCR. Results: SeHCAT 7d retention values were 15% in 9 who were normal diarrhea controls. Previous studies had shown no significant difference in baseline unstimulated FGF19 expression between these groups and this was confirmed with the unstimulated control samples (p=0.76). Median stimulation overall was 184-fold with CDCA and 373-fold with GCDCA. A positive correlation was found between SeHCAT retention and the magnitude of the fold change in FGF19 expression stimulated by either CDCA (r=0.50, n=16, p=0.02) or by GCDCA (r=0.76, n=7, p=0.02). These relationships were still present when the fold changes were normalized to the baseline FGF19 expression found in the unstimulated explants. Conclusion: Ileal explants from patients with lower SeHCAT 7d retention have a lower response to both CDCA and GCDCA. As uptake of GCDCA is dependent on carrier-mediated apical BA uptake but CDCA is not, this implies there is no defect in apical BA uptake, but abnormalities elsewhere in the FGF19 response. A reduced capacity to induce ileal FGF19 expression in response to absorbed BA is proposed to lead to the excess BA production and fecal BA losses found in primary BAD.

313 Effects of Rifaximin on Urgency, Bloating, and Abdominal Pain in Patients With IBS-D: A Randomized, Controlled, Repeat Treatment Study

of these patients had fasting FGF19 measured. Alanine transaminase (ALT) and appearance of fatty liver on imaging (ultrasound, CT or MR) were retrospectively added to the database. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Patients with known chronic liver disease or alcohol abuse were excluded from the final analysis. Results: Of 578 SeHCAT values on the database, 303 (52%) were positive with a value 31IU/L (36% v 21%, p 31IU/L (21% v 7%, p 31IU/L (43% v 22%, p 31IU/L (23% v 7%, p 40 IU/L (40% vs 12%, p<0.05), OR 5.13 (95%CI 1.28-20.61, p<0.05). Conclusions: Primary bile acid diarrhea is associated with NAFLD and may share a common pathology in low FGF19. Both conditions may be presentations of the metabolic syndrome associated with low FGF19.

311 Large Scale Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome

of these patients had fasting FGF19 measured. Alanine transaminase (ALT) and appearance of fatty liver on imaging (ultrasound, CT or MR) were retrospectively added to the database. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Patients with known chronic liver disease or alcohol abuse were excluded from the final analysis. Results: Of 578 SeHCAT values on the database, 303 (52%) were positive with a value 31IU/L (36% v 21%, p 31IU/L (21% v 7%, p 31IU/L (43% v 22%, p 31IU/L (23% v 7%, p 40 IU/L (40% vs 12%, p<0.05), OR 5.13 (95%CI 1.28-20.61, p<0.05). Conclusions: Primary bile acid diarrhea is associated with NAFLD and may share a common pathology in low FGF19. Both conditions may be presentations of the metabolic syndrome associated with low FGF19.

312 Efficacy and Safety of ASP7147, a Bombesin-2 Receptor Antagonist, in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D): Results of a Multicenter, Double-Blind, Placebo-Controlled Trial

of these patients had fasting FGF19 measured. Alanine transaminase (ALT) and appearance of fatty liver on imaging (ultrasound, CT or MR) were retrospectively added to the database. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Patients with known chronic liver disease or alcohol abuse were excluded from the final analysis. Results: Of 578 SeHCAT values on the database, 303 (52%) were positive with a value 31IU/L (36% v 21%, p 31IU/L (21% v 7%, p 31IU/L (43% v 22%, p 31IU/L (23% v 7%, p 40 IU/L (40% vs 12%, p<0.05), OR 5.13 (95%CI 1.28-20.61, p<0.05). Conclusions: Primary bile acid diarrhea is associated with NAFLD and may share a common pathology in low FGF19. Both conditions may be presentations of the metabolic syndrome associated with low FGF19.

OC-026 Diagnostic Yields Of Sehcat Scanning And Glucose Hydrogen Breath Testing In Pelvic Radiation Disease

IntroductionLate Gastrointestinal side effects following radiotherapy are common but under reported by patients and poorly recognised by clinicians.1 Pelvic radiation disease (PRD) can present up to 30 years after radiotherapy...

PTH-108 Sehcat: Nice Or Not Nice?

IntroductionBile acid malabsorption (BAM) is increasingly recognised as the underlying diagnosis in many patients with D-IBS and Crohn’s disease, and SeHCAT testing has greatly increased. The 2012 NICE consultation document...

OC-027 Fgf19 Levels In Subjects With Primary Bile Acid Diarrhoea And Elevated Triglycerides

IntroductionThere is evidence that primary bile acid diarrhoea (PBAD) is caused by disordered bile acid homeostasis. Most patients with severe PBAD have low fasting serum FGF19 which fails to rise...

PTH-110 Factors Predictive Of Bile Acid Diarrhoea And Long Term Treatment Outcomes

IntroductionBile acid diarrhoea (BAD) is a recognised cause of chronic diarrhoea, however detection remains sub-optimal. Knowledge of factors predictive of BAD could help improve detection. This study evaluates factors predictive...

Mo1972 Role of SeHCAT Scanning in Diagnosis of Bile Salt Malabsorption: a University Hospital Experience

Introduction: Chronic diarrhoea is a very common presentation in the gastroenterology clinics. Majority of patients with negative investigations for organic disease are often labelled with a diagnosis of irritable bowel syndrome with diarrhoea (IBS-D). Bile salt malabsorption (BMA) is not an uncommon cause of chronic diarrhoea. In clinical practice mostly an empirical trail of bile acid sequestrants is used to diagnose this condition which lacks diagnostic accuracy. 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scan is a reliable, simple and non invasive investigation to detect and treat this condition but has been underutilized in most centres in the United Kingdom (UK). Aims & Methods: We aimed to evaluate the usefulness of SeHCAT scan in evaluating patients with chronic diarrhoea. We retrospectively reviewed all patients who had SeHCAT scan over a two year period in a University Hospital. The integrated hospital electronic database system was reviewed and analysed for the following: clinical details, radiology, biochemistry, endoscopy and histology. BMA was defines as SeHCAT retention of less than 15% (mild 10-15%; moderate 5-10% and severe <5%). Results: 118 patients referred to gastroenterology clinic for chronic diarrhoea underwent SeHCAT testing over the review period. 42 M; 76 F, mean age 51 y (range 16-89). SeHCAT test was positive for BMA in 51/118(43%) of patients. Among positive SeHCAT tests, 27 (53%) had severe, 15 (29%) had moderate and, 9 (17%) had mild BAM. 12 (23%) had type 1 (6 terminal ileal resection and 6 Crohn's Disease), 28 (55%) had type 2 (Idiopathic) and 11 (21.5%) had type 3 (7 cholecystectomy, 2 diabetes, 2 coeliac) BAM. Out of 51 with confirmed BMA on SeHCAT testing, treatment information in the notes was available for 35(68%) of the patients. These patients were treated with bile acid sequestrants, either with colesevalam (n=7) or with cholestyramine (n=28). Colesevalam was well tolerated with 100% good response. In cholestyramine group 12(43%) had good response, 4(7%) partial and 7(25%) showed poor response. All patients with poor response discontinued treatment and 4 (57%) of this group stopped cholestyramine early due to unpleasant side effects. No treatment response was documented in the notes for 5 patients. Overall, colesevalam had excellent response rates with no reported side effects. Conclusion: SeHCAT scan is probably an underutilized test for diagnosing bile salt malabsorption. In patients presenting with chronic diarrhoea SeHCAT scanning must be considered to diagnose this probably under recognised cause of chronic diarrhoea. Colesevalam has better tolerability and response rates and must be considered in group of patients intolerant to cholestyramine.

Systematic review: the management of chronic diarrhoea due to bile acid malabsorption

Bile acid malabsorption (BAM) is a common, yet under-recognised, cause of chronic diarrhoea, with limited guidance available on the appropriate management of patients with BAM. To summarise the evidence supporting different treatments available for patients with bile acid malabsorption, noting their impact on clinical outcomes, tolerability and associated side effects. A literature search was conducted through PubMed, the Cochrane Database of Systematic Reviews and Scopus. Relevant articles studied patients who had been diagnosed with BAM and were clinically assessed before and after therapy. A total of 30 relevant publications (1241 adult patients) were identified, which investigated the clinical response to drugs, including colestyramine, colestipol, colesevelam, aluminium hydroxide and obeticholic acid. The most commonly used diagnostic test of bile acid malabsorption was the SeHCAT test (24 studies). Colestyramine treatment was by far the most studied of these agents, and was successful in 70% of 801 patients (range: 63-100%). Colestyramine and colestipol are generally effective treatments of gastrointestinal symptoms from BAM, but may be poorly tolerated and reduce the bioavailability of co-administered agents. Alternative therapies (including colesevelam and aluminium hydroxide) as well as dietary intervention may also have a role, and the promising results of the first proof-of-concept study of obeticholic acid suggest that its novel approach may have an exciting future in the treatment of this condition. Future trials should employ accurate diagnostic testing and be conducted over longer periods so that the long-term benefits and tolerability of these different approaches can be evaluated.