SeHCAT Test Research Articles

Bile acid malabsorption investigated by selenium-75-homocholic acid taurine (75SeHCAT) scans, a retrospective single-centre experience.

Bile acid malabsorption (BAM) is a common entity in patients experiencing chronic watery diarrhea. However, literature suggests that BAM is underdiagnosed and undertreated. In many countries 75SeHCAT is the gold standard for diagnosing BAM (1-5). The aim of this retrospective study was to investigate the frequency of BAM using 75SeHCAT scintigraphy and the response to treatment with bile acid sequestrants. We retrospectively evaluated the clinical data of 420 patients who had a 75SeHCAT scan from January 2016 to January 2023. Electronic medical records were investigated for risk factors of BAM. BAM was defined as a 75SeHCAT retention of less than 15%. Response to bile acid sequestrants was evaluated based on outpatient clinical reports. Median age at the time of 75SeHCAT test was 47 years (range 14-87). Out of 420 patients, 192 (46%) had a positive result for BAM. Cholecystectomy and ileal resection were significant predictors for BAM (p<0.001). BAM type 1 is statistically more likely to be more severe compared to type 2 (p<0.0001) and compared to type 3 (p=0.0021). In patients who fulfilled Rome IV criteria for IBS-D or functional diarrhea, 75 out of 121 (38%) tested positive for BAM. Overall, treatment with bile acid binders was effective in 76%. This retrospective study of patients who underwent SeHCAT scanning confirms that about 1/3 patients presenting with therapy-resistant chronic diarrhea in secondary care suffer from BAM. Including the test in clinical management protocols of chronic diarrhea allows early and quantitative diagnosis and treatment of BAM.

SeHCAT retention measurements may be compromised by traces of 177 Lu/ 177m Lu more than 90 days after 177 Lu-DOTATATE was administered.

[ 75 Se]tauroselcholic acid (SeHCAT) retention measurement provides a noninvasive test for bile acid diarrhea (BAD); however, it is sensitive to the presence of other radionuclides. Two SeHCAT patients at the Royal Free Hospital (RFH) had significant discrepancies between the lower photopeak (111-159 keV) and central photopeak (242-296 keV) windows, indicating contamination with a radionuclide other than 75 Selenium. These patients had received lutetium-177 oxodotreotide ( 177 Lu-DOTATATE) therapy 98 and 151 days before their SeHCAT tests. Traces of 177 Lu may be retained longer than typically modeled, along with the contaminant 177m Lu. This work includes a retrospective audit to examine the prevalence of SeHCAT tests being affected by 177 Lu and phantom measurements to investigate the potential impact. Of 579 patients who received 177 Lu-DOTATATE therapy at our center, 11 subsequently attended for a SeHCAT test. The two previously identified patients may have had compromised SeHCAT results; however, the other patients had longer intervals between their therapy and test, and their tests are believed to be valid. Spectra were acquired from a phantom containing either a SeHCAT capsule or a mixture of 177 Lu/ 177m Lu representative of a patient >90 days after their treatment. The SeHCAT spectrum was scaled to produce simulated day-7 spectra, and the SeHCAT retention that would have been calculated if 177 Lu/ 177m Lu were present was determined. All SeHCAT measurement windows are affected by the 177 Lu/ 177m Lu, producing clinically significant errors. Patients requiring SeHCAT testing should be asked whether they have ever received 177 Lu-DOTATATE. Patient-specific background measurements may be useful for checking for significant levels of other radionuclides.

Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study.

We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test. Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

The Epidemiology of Bile Acid Diarrhea in Denmark.

Bile acid diarrhea (BAD) is a socially debilitating disease with frequent bowel movements, urgency, and fecal incontinence as the main symptoms. It is caused by excessive bile acid levels in the colon and is most commonly treated with bile acid sequestrants. It is estimated that 1-2% of the population suffers from the disease, but only a fraction of these are properly diagnosed with the gold standard ⁷⁵selenium-homotaurocholic acid (SeHCAT) test. Here, we use nationwide registries to describe the demographic characteristics of individuals suffering from BAD in Denmark. Since the International Classification of Diseases diagnosis code for BAD was not used until 2021, we identified the BAD population by referral to SeHCAT testing followed by a prescription of a bile acid sequestrant (colestyramine, colestipol or colesevelam) within 365 days. The study period was from 2003 to 2021. During the study period, a total of 5264 individuals with BAD were identified with large differences between the five regions in Denmark. The number of prescriptions of colestyramine and colesevelam, the number of SeHCAT tests, and the number of individuals diagnosed with BAD increased during the study period. The BAD population had more co-morbidities and more health care contacts as well as lower levels of education and income compared with age- and sex-matched controls from the general population. Using the Danish registries, we identified a BAD population, which seems to be inferior in health care and socio-economic parameters compared with the Danish general population.

B-190 Development of an LC-MS/MS Method for Analysis of 7α-hydroxy-4-cholesten-3-one and Investigation Into its Utility as a Biomarker for Bile Acid Diarrhoea in the United Kingdom

Abstract Background Bile Acid Diarrhoea (BAD) is a common gastrointestinal condition estimated to affect 1% of the population. It is, however, significantly under-diagnosed. This is partly due to lack of diagnostic methods. In the United Kingdom (UK) the 75-SeHCAT retention scan is considered the gold-standard diagnostic method and is the only routinely available diagnostic test for BAD. SeHCAT retention of &amp;lt;15% is considered consistent with BAD. The SeHCAT test is, however, expensive, time consuming, and exposes the patient to a dose of radiation. 7-alpha-hydroxy-4-cholesten-3-one (7αC4) is a precursor in the bile acid synthesis pathway and has demonstrated utility as a marker of BAD. There is limited data comparing 7αC4, which is measured in the United States, to the SeHCAT test, as SeHCAT is not licensed in the United States. 7αC4 can be measured by LC-MS/MS, thus can provide a more convenient, low cost and high throughput option for diagnosis of BAD. Aims 1) To develop and validate an LC-MS/MS method for analysis of 7αC4. 2) To analyse serum samples taken from patients referred for SeHCAT scans. 3) To determine the utility of 7αC4 compared to SeHCAT for diagnosis of BAD. Methods The method was adapted from Donato et al. 750 µL of ice-cold acetonitrile containing 50 nmol/L D7-7αC4 as internal standard was added to 250 µL serum. Samples were vortexed for 30 s, centrifuged at 3000g for 10 min, and supernatant transferred into a vial for LC-MS/MS analysis. The LC-MS/MS system utilised a Gemini 5um NX-C18 column coupled to a Sciex 6500 TripleQuad mass spectrometer. Ethical approval was obtained to collect serum on patients undergoing SeHCAT retention scans for investigation of BAD. 40 patients who attended for SeHCAT scans had serum collected and stored at −80 degrees Celsius until analysis for 7αC4. Sensitivity and specificity of 7αC4 was calculated and ROC curve analysis performed. Results The 7αC4 method demonstrated an LoQ of 1.5 nmol/L, linearity up to 1095 nmol/L, and intra-assay %CV of 3.0%–7.7%. Using SeHCAT retention of &amp;lt;15% as positive for BAD, ROC curve analysis demonstrated an AUC of 0.765. 7aC4 at a concentration of 175 nmol/L provided a sensitivity of 30% and a specificity of 92%. 7αC4 at a concentration of 50 nmol/L provided a sensitivity of 93% and a specificity of 46%. Conclusion The 7αC4 method demonstrated good analytical performance and was suitable for use in a routine laboratory. 7αC4 results of &amp;lt;50 nmol/L suggest BAD is unlikely, and results of &amp;gt;175 nmol/L make a diagnosis of BAD likely. Results in between these two values may be considered indeterminate and referral for SeHCAT scanning may be considered appropriate. The 7αC4 assay provides an opportunity to stratify patients for SeHCAT testing in the UK, improving diagnosis and management of BAD in patients with chronic diarrhoea and streamlining the patient pathway.

Efficacy and safety of colesevelam for the treatment of bile acid diarrhoea: a double-blind, randomised, placebo-controlled, phase 4 clinical trial

Bile acid diarrhoea is a common but overlooked cause of chronic watery diarrhoea. Plasma 7α-hydroxy-4-cholesten-3-one (C4) is an alternative to the gold standard tauroselcholic [75Se] acid (SeHCAT) test. Low-certainty evidence supports sequestrant treatment, including colesevelam. We aimed to determine the efficacy and safety of colesevelam in bile acid diarrhoea. In this randomised, double-blind, placebo-controlled, investigator-initiated phase 4 trial of the sequestrant colesevelam in bile acid diarrhoea (SINBAD), we enrolled consecutive patients aged 18-79 years without inflammatory bowel disease attending SeHCAT testing for suspected bile acid diarrhoea at four Danish secondary care centres. Participants were randomly allocated 1:1 to receive 12 days of treatment with colesevelam (overencapsulated tablets of 625 mg) or placebo, with the starting dose of two capsules twice daily and titrated to effect during the first 5 days of treatment. A pharmacist independent of the clinical investigators generated a randomisation list on the web page randomization.com using block randomisation (randomisation was not stratified). C4 and SeHCAT diagnostic results were blinded during treatment. We treated all patients with diarrhoea, with a daily mean of 3·0 or more bowel movements or 1·0 or more watery bowel movements (Bristol stool scale type 6 and 7). Remission was defined as the absence of both these criteria during treatment days 6-12. The primary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by C4 concentration greater than 46 ng/mL. A secondary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by SeHCAT retention of 10% or less. This trial is registered with ClinicalTrials.gov, NCT03876717. Between Oct 25, 2018, and July 1, 2021, 168 patients were randomly assigned to receive colesevelam (n=84) or placebo (n=84). 41 patients had C4 concentration greater than 46 ng/mL (22 assigned to the colesevelam group and 19 to the placebo group). For the C4-defined primary outcome, 14 (64%) of 22 participants receiving colesevelam versus three (16%) of 19 participants receiving placebo achieved remission (adjusted odds ratio 9·1, 95% CI 1·9-62·8; p=0·011). For the SeHCAT-defined secondary outcome, 75 of the 168 participants had retention of less than 10% (37 assigned to the colesevelam group and 38 assigned to the placebo group); 22 (59%) of 37 participants receiving colesevelam achieved remission versus five (13%) of 38 participants receiving placebo (adjusted odds ratio 11·1, 95% CI 3·4-45·6; p=0·00020). There were no serious adverse events. Common adverse events were transient. For patients receiving colesevelam within the primary outcome population, five had abdominal pain, nine had bloating, and four had nausea. For patients receiving placebo, four had abdominal pain, four had bloating, and one had nausea. No participants with bile acid diarrhoea withdrew due to adverse events. Colesevelam was superior to placebo at inducing remission of bile acid diarrhoea diagnosed with C4 concentration greater than 46 ng/mL. Secondary outcome data suggest similar efficacy treating SeHCAT-defined bile acid diarrhoea. Colesevelam was safe during the treatment. Fabrikant Vilhelm Pedersen og hustrus mindelegat; recommended by the Novo Nordisk Foundation.

SeHCAT (tauroselcholic [75selenium] acid) for the investigation of bile acid diarrhoea in adults: a systematic review and cost-effectiveness analysis

Background Tauroselcholic [75selenium] acid (SeHCAT™) (GE Healthcare, Chicago, IL, USA) is a radiopharmaceutical that may be useful in diagnosing bile acid diarrhoea. Objectives To assess the clinical effectiveness and cost-effectiveness of SeHCAT for the investigation of adults with chronic unexplained diarrhoea, diarrhoea-predominant irritable bowel syndrome or functional diarrhoea (suspected primary bile acid diarrhoea), and adults with chronic diarrhoea and Crohn’s disease who have not undergone ileal resection (suspected secondary bile acid diarrhoea). Methods Sixteen databases were searched to November 2020. The review process included measures to minimise error and bias. Results were summarised by primary or secondary bile acid diarrhoea and study quality was considered. The cost-effectiveness analysis combined a short-term (6-month) decision-analytic model (diagnosis and initial treatment response) and a lifetime Markov model comprising three health states (diarrhoea, no diarrhoea and death), with transitions determined by probabilities of response to treatment. Analyses were conducted from an NHS and Personal Social Services perspective. Results Twenty-four studies were included in this review. Of these, 21 were observational studies, reporting some outcome data for patients treated with bile acid sequestrants, and in which only patients with a positive SeHCAT test were offered bile acid sequestrants. The median rate of response to bile acid sequestrants, among patients with a 7-day SeHCAT retention value of ≤ 15%, was 68% (range 38–86%) (eight studies). The estimated sensitivity of SeHCAT (≤ 15% threshold) to predict positive response to colestyramine was 100% (95% confidence interval 54.1% to 100%) and the specificity estimate was 91.2% (95% confidence interval 76.3% to 98.1%) (one study). The median proportion of treated patients who were intolerant/discontinued bile acid sequestrants was 15% (range 4–27%) (eight studies). There was insufficient information to determine whether or not intolerance varied between colestyramine, colestipol and colesevelam. For both populations, the SeHCAT 15% (i.e. a SeHCAT retention value of ≤ 15%) strategy dominated other strategies or resulted in incremental cost-effectiveness ratios of &lt; £20,000–30,000 per quality-adjusted life-year gained. For the suspected primary bile acid diarrhoea population, SeHCAT 15% was the strategy most likely to be cost-effective: 67% and 73% probability at threshold incremental cost-effectiveness ratios of £20,000 and £30,000 per quality-adjusted life-year gained, respectively. For the Crohn’s disease population, these probabilities were 89% and 92% at £20,000 and £30,000 per quality-adjusted life-year gained, respectively. Cost-effectiveness was mostly led by treatment response. SeHCAT 15% was the strategy with the highest response rate in the majority of scenarios explored. Limitations and conclusions There is a lack of evidence linking the use of SeHCAT testing to patient-relevant outcomes. The optimal SeHCAT threshold, to define bile acid diarrhoea and select patients for treatment with bile acid sequestrants, is uncertain. It is unclear whether or not patients with ‘borderline’ or ‘equivocal’ 7-day SeHCAT retention values (e.g. between 10% and 15%) and patients with values of &gt; 15% could benefit from treatment with bile acid sequestrants. Although the results of the economic evaluation conducted for both populations indicated that the SeHCAT 15% strategy dominated the other two strategies or resulted in incremental cost-effectiveness ratios that were lower than the common thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, the paucity and poor quality of evidence mean that uncertainty is high. Future work The optimum study design would be a multiarm randomised controlled trial, in which participants meeting the inclusion criteria are randomised to receive colestyramine, colestipol, colesevelam or placebo, and all participants receive SeHCAT testing. Study registration This study is registered as PROSPERO CRD42020223877. Funding This project was funded by the National Institute for Health and Care Research (IHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 45. See the NIHR Journals Library website for further project information.

Malabsorpce žlučových kyselin u onkologických pacientů

Summary: Bile acid malabsorption (BAM) is caused by dysregulation of enterohepatic circulation of bile acids and their synthesis in the liver. Estimated prevalence is about 1% of adult population. BAM has been substantially underdiagnosed. This condition can be present in one third of patients with diarrhoea-predominant irritable bowel syndrome and in 50–100% of Crohn‘s disease with ileitis or previously resected terminal ileum. Up to one half of oncology patients with pelvic radiotherapy suffer from BAM. SeHCAT test (75Selenium HomoCholic Acid Taurine test) is the gold diagnostic standard and the test has just become available in the Czech Republic. Low-fat diet is the most important dietary modification. Bile acids sequestrants (cholestyramine in the Czech Republic) are the crucial part of pharmacotherapy. Key words: bile acid malabsorption – SeHCAT test – cholestyramine

A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients

This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn’s disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6–4.2), BAD (3.6; 1.9–7.2) and post-cholecystectomy cohort 3.8 (2.3–6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn’s disease cohort (11.8; 10.1–16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6–10.5) and < 5% (9.9; 4.8–15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6–4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn’s patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.

P202 Performance characteristics of serum FGF19 measurement compared with the Se-HCAT retention test in the diagnosis of bile acid diarrhoea in Crohn’s Disease

Abstract Background Bile acid diarrhoea (BAD) is common in patients with Crohn’s disease (CD), but its recognition is challenging since symptoms are similar to those of active inflammatory disease. The current clinical gold standard for diagnosing BAD is the Se-HCAT test, however, it is inconvenient to the patient and has limited availability. FGF19 is a hormone produced in the enterocytes of the ileum in response to absorbed BAs. Serum FGF19 levels are a direct marker of BA absorption, and they are reduced in BAD. The aim of this study was to evaluate the performance of FGF19 as a diagnostic tool for BAD in Crohn’s disease. Methods Fasting serum FGF19 levels and Se-HCAT retention were measured before bowel preparation in 63 consecutive Crohn’s disease patients referred for an ileocolonoscopy. Clinical, endoscopic and biologic data were prospectively recorded. BAD was defined as an abdominal retention &amp;lt;10% and severe BAD as &amp;lt;5% at day seven. Results BAD was present in 60% of non-resected CD (NR-CD) patients and in 93% of ileal-resected (IR-CD) patients. FGF19 levels were lower in IR-CD patients (median 23 pg/ml; IQR, 3–44) than in the NR-CD patients (61 pg/ml; IQR, 18–121) (p = 0.02). FGF19 levels were inversely related with ileal resection length in IR-CD patients (rs = -0.52, P = 0.01). FGF19 and Se-HCAT values were positively related (rs = 0.57, P &amp;lt; 0.0001), whereas FGF19 was inversely related with the number of bowel movements (rs = -0.31, P=0.01) and Bristol scale (rs = -0.27, P= 0.04). No significant relation was found between FGF19 and clinical (CDAI) nor endoscopic (SES-CD) scores. Area under the ROC curve for FGF19 to detect SeHCAT at &amp;lt;10% and &amp;lt;5% were 0.75 (95% CI 0.62–0.88) and 0.81 (95% CI 0.71–0.92) respectively. Conclusion Serum FGF19 can be used as a simple blood test to the diagnostic of BAD in CD. FGF19 measurement could be an adjunct in guiding treatments for diarrhoea in CD.

1134 Incidence of Bile Acid Diarrhoea Post-Cholecystectomy - A Single Centre Cohort

Abstract Aim Bile acid diarrhoea (BAD) can occur as a result of enterohepatic circulation interruption following cholecystectomy. Although up to 57.2% of patients are reported to develop post-cholecystectomy diarrhoea, this is not always because of BAD. The aim of this study was to determine the incidence of post-cholecystectomy BAD diagnosis and evaluate the current practices. Method This study was conducted as part of BADCAP study. The electronic records of patients underwent cholecystectomy operation at Oxford University Hospitals between January 2013 and December 2017 were retrospectively analysed. Records were matched with patients who underwent 75SeHCAT testing during the same time period. A positive 75SeHCAT testing was defined as a seven-day retention time of &amp;lt; 15%. Results A total of 4327 patients underwent cholecystectomy operation. 2.05% (N = 89) investigated for diarrhoea by 75SeHCAT. Alongside 75SeHCAT, 69.7% (N = 62) had colonoscopy, 37.1% (N = 33) had CT abdomen and pelvis and 3.4% (N = 3) had MRCP/MRE. Gender wise statistics revealed females were 74.5% (N = 73) and males were 19.1% (N = 17). Median time from cholecystectomy to 75SeHCAT test was 780 days (SD +/-510 days). 70.8% (N = 63) had a positive 75SeHCAT test for BAD. IBD was confirmed in 2.2% (N = 2). Conclusions A small number of patients were investigated and only 1.5% were diagnosed with post-cholecystectomy diarrhoea. There was a significant time delay from operation to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher and clinicians need to have an increased awareness of this condition. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

75SeHCAT whole body retention for unexplained chronic diarrhoea based on early first whole body counting.

There are many protocol variations in the whole-body 75SeHCAT retention test [whole-body retention (WBR)] for investigation of bile acid diarrhoea. The time between capsule consumption and first count, however, is widely taken, without debate, to be 3 h. In the Covid-19 era, it is desirable to limit the time patients spend in the department. We, therefore, questioned the need for a 3 h interval between capsule administration and the initial count. Using an uncollimated gamma camera, whole-body counting was performed at 5, 30 and 180 min after capsule ingestion in 24 patients with chronic diarrhoea. Geometric mean was taken of counts acquired from posterior and anterior projections. WBR was expressed as the ratio of 7 day-to-initial whole-body counts (%) to give WBR5, WBR30 and WBR180. A small meal was given at 60 min after capsule ingestion. There was a close correlation between WBR30 and WBR180 (y = 1.0x - 0.29%; r = 0.99). For WBR180 values of <15% (lower limit of normal), there was close agreement between WBR30 and WBR180 (bias 0.03%; precision 0.7%). WBR5 overestimated WBR180. However, cWBR5, obtained by multiplication of WBR5 by 0.75, also correlated closely with WBR180 (y = 1.2x - 4.5%; r = 0.97), and there was close agreement between cWBR5 and WBR180 for WBR180 values <15% (bias 0.08%, precision 1.3%). The first whole-body count in the 75SeHCAT test can be undertaken at 30 min postcapsule without loss of accuracy, or even 5 min if only subnormal values are considered relevant. No food is required after capsule consumption.

Single scan SeHCAT studies: a model for the prediction of the 3-h counts.

As part of the 75-Selenium homocholic acid taurine (SeHCAT) study, counts are acquired as a baseline to allow the calculation of the retention at 7 days. In this work, we evaluated whether it was possible to replace the baseline image with a predictive model based on the patient's height and weight. Height and weight data from 723 patients scanned at three hospitals using seven gamma cameras were compiled. A number of different models were trialled, with fitting parameters determined by regression. A predictive model based on height and logarithm of weight was found to have the best correlation with the measured counts in the 3-h study. There was a strong correlation (R2 = 0.91) between the measured counts and the predicted counts using a model based on height and logarithm of weight. Treating the standard SeHCAT test result as the gold standard, the test result when predicted baseline counts were used had a sensitivity and specificity of 97.5 and 98.0%, respectively, at a threshold of 15%. In total 694/723 (96.0%) of patients had no change to their severity grading when using the predicted baseline counts. This work presents a model that was able to predict the counts in the 3 h SeHCAT study for patients on seven gamma cameras. This can enable a single scan study, giving significant savings to patient and staff time and imaging resources.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit

IntroductionBile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1–57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices.MethodsA retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05).ResultsA total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days).Discussion/ConclusionOnly a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

SeHCAT test for bile acid malabsorption: may “the old” become “the gold one” in the diagnostic burden of chronic diarrhea?

SeHCAT test for bile acid malabsorption: may “the old” become “the gold one” in the diagnostic burden of chronic diarrhea?

Bile acid diarrhea, stepchild of chronic diarrhea - prevalence, diagnosis and treatment. Update 2021

Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.

Prevalence of biliary acid malabsorption in patients with chronic diarrhoea of functional characteristics: a prospective study

BackgroundBile 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.MethodsThis 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 diarrhoeaResults38 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.ConclusionsBile 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.

The pathophysiology of bile acid diarrhoea: differences in the colonic microbiome, metabolome and bile acids

Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with diarrhoea (IBS-D). The gut microbiota metabolises primary BAs to secondary BAs, with differing impacts on metabolism and homeostasis. The aim of this study was to profile the microbiome, metabolic products and bile acids in BAD. 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 volatile organic compounds (VOCs) were measured. BAs were quantified in serum and faeces. Faecal bacterial diversity was significantly reduced in patients with BAD. 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, but the greatest discrimination was between IBS-D and controls. Unconjugated and primary BA in serum and faeces were significantly higher in BAD. The faecal percentage primary BA was inversely related to SeHCAT. BAD produces dysbiosis, with metabolite differences, including VOC, SCFA and primary BAs when compared to IBS-D. These findings provide new mechanistic insights into the pathophysiology of BAD.

High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria.

BackgroundA high prevalence of primary bile acid diarrhoea (BAD) has been reported for Rome III defined irritable bowel syndrome (IBS)-diarrhoea and functional diarrhoea. We determined whether this still applies under the contemporaneous Rome IV criteria, given that the latter characterises IBS-diarrhoea as having more frequent abdominal pain compared with previous iterations, whilst no longer recognising abdominal discomfort.MethodsPatients referred for a 75SeHCAT test completed a baseline questionnaire comprising, i) demographic data, ii) risk factors for BAD (inflammatory bowel disease, bowel resection, cholecystectomy, microscopic colitis, celiac disease, abdominal-pelvic radiotherapy), iii) the Rome III and IV bowel disorder questionnaire, and iv) mood and somatisation scores. A diagnosis of BAD constituted a 75SeHCAT of ≤15%, with moderate to severe disease being defined as ≤10% and ≤5%, respectively.FindingsOf 300 patients with complete dataset, 184 had no risk factors for BAD and fulfilled criteria for either IBS-diarrhoea or functional diarrhoea. The prevalence of primary BAD was 38% (n = 70/184), with almost half having moderate (n = 16) to severe (n = 17) disease. Using the Rome III criteria, the prevalence of primary BAD was 36% in IBS-diarrhoea (n = 63/173) and 64% (n = 7/11) in functional diarrhoea; p = 0.11. Using the Rome IV criteria, the prevalence of primary BAD was 38% (n = 53/139) in IBS-diarrhoea and 38% (n = 17/45) in functional diarrhoea; p = 0.97. Patients with primary BAD experienced more frequent loose stools (p = 0.01) and had a higher body mass index (p<0.0001) compared to those without BAD, but otherwise no significant differences were seen in age, gender, mood, somatisation, or abdominal pain. The presence of primary BAD in patients classified as overweight or obese was approximately 40% and 60%, respectively.InterpretationOver a third of patients with Rome IV IBS-diarrhoea or functional diarrhoea have primary BAD, similar to Rome III. We therefore recommend that, in secondary care settings, generic testing for primary BAD should be considered in patients presenting with chronic diarrhoea of presumed functional origin regardless of concomitant abdominal pain. Centres that lack tests for primary BAD, and who empirically treat instead, may consider targeting patients who are overweight or obese.

Fecal Bile Acid Testing in Assessing Patients With Chronic Unexplained Diarrhea: Implications for Healthcare Utilization.

Bile acid (BA) diarrhea is the cause in ∼26% of chronic unexplained (nonbloody) diarrhea (CUD) based on SeHCAT testing. To assess fecal BA excretion and healthcare utilization in patients with CUD. In a retrospective review of 1,071 consecutive patients with CUD who completed 48-hour fecal BA testing, we analyzed the symptoms, diagnostic tests performed, and final diagnoses. After 135 patients were excluded because of mucosal diseases, increased BA excretion was identified in 476 (51%) of the 936 patients with CUD: 29% with selective increase in primary BA and 22% with increased total BA excretion (35% with normal primary BA excretion). There were no differences in demographics, clinical symptoms, or history of cholecystectomy in patients with elevated total or selective primary fecal BA excretion compared with patients with normal excretion. Before the 48-hour fecal BA excretion test was performed, patients completed on average 1.2 transaxial imaging, 2.6 endoscopic procedures, and 1.6 miscellaneous tests/person. Less than 10% of these tests identified the etiology of CUD. Total fecal BAs >3,033 µmol/48 hour or primary BAs >25% had a 93% negative predictive value to exclude mucosal disease. Among patients with increased fecal BA excretion, >70% reported diarrhea improved with BA sequestrant compared with 26% with normal fecal BA excretion. Patients with selective elevation in primary fecal BAs were 3.1 times (95% confidence interval, 1.5-6.63) more likely to respond to BA sequestrant therapy compared with those with elevated total fecal BAs. Increased fecal BA excretion is frequent (51%) in patients with CUD. Early 48-hour fecal BA evaluation has the potential to decrease healthcare utilization in CUD.