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Keywords:

  • bile acid malabsorption;
  • diarrhea;
  • irritable bowel syndrome;
  • SeHCAT scan

Abstract

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

Background  Many physicians do not consider the diagnosis of bile acid malabsorption in patients with chronic diarrhea, or do not have access to testing. We examined yield of 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning in chronic diarrhea patients, and attempted to identify predictors of a positive test.

Methods  Consecutive patients with chronic diarrhea undergoing SeHCAT scan over a 7-year period were identified retrospectively. Bile acid malabsorption was defined as present at a retention of <15%. Medical records were reviewed to obtain information regarding proposed risk factors. Gastrointestinal symptoms were recorded, and patients were classified as having diarrhea-predominant irritable bowel syndrome (IBS-D) if they reported abdominal pain or discomfort. Independent risk factors were assessed using multivariate logistic regression, and odds ratios (ORs) with 99% confidence intervals (CIs) were calculated.

Key Results  Of 373 patients, 190 (50.9%) had bile acid malabsorption. Previous cholecystectomy (OR 2.51; 99% CI 1.10–5.77), terminal ileal resection or right hemicolectomy for Crohn’s disease (OR 12.4; 99% CI 2.42–63.8), and terminal ileal resection or right hemicolectomy for other reasons (OR 7.94; 99% CI 1.02–61.6) were associated with its presence. Seventy-seven patients had IBS-D, and 21 (27.3%) tested positive. There were 168 patients with no risk factors for a positive SeHCAT scan, other than chronic diarrhea, and 63 (37.5%) had bile acid malabsorption.

Conclusions & Inferences  Bile acid malabsorption was present in 50% of patients undergoing SeHCAT scanning. Almost 40% of those without risk factors had evidence of bile acid malabsorption, and in those meeting criteria for IBS-D prevalence was almost 30%.

Abbreviations:
CI

confidence interval

IBS-D

diarrhea-predominant irritable bowel syndrome

OR

odds ratio

SeHCAT

23-seleno-25-homo-tauro-cholic acid

SD

standard deviation

Chronic diarrhea occurring as a result of bile salts entering the colon, so-called bile acid malabsorption, was first described in 1967.1 The condition is classified according to underlying etiology: with type I representing failure to reabsorb bile acids in the terminal ileum due to either resection or localized disease; type III due to miscellaneous causes including previous cholecystectomy, fibrosis after radiotherapy, following acute enteric infection, or in association with other conditions such as celiac disease or microscopic colitis; and type II, or idiopathic, where no cause is apparent.2 In the latter case, the term bile acid malabsorption may be a misnomer, as evidence suggests that bile acid uptake in the terminal ileum is actually normal or increased,3 with the total bile acid pool increased due to impaired negative feedback of bile acids on fibroblast growth factor 19,4 and this may be best referred to as bile acid diarrhea.

Abnormalities of the enterohepatic circulation of bile acids can be assessed with a therapeutic trial of a bile acid sequestrant, fecal bile acid or serum 7α-hydroxy-4-cholesten-3-one measurement, or 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning, using 75Selenium-homocholyltaurine.5 Despite studies reporting bile acid malabsorption as the underlying cause in 30–70% of patients with chronic diarrhea undergoing SeHCAT scanning,6–10 UK national guidelines for the management of patients with chronic diarrhea do not recommend routine testing, only in those where the index of suspicion for underlying organic disease is high.11 There is even evidence to suggest that many clinicians do not perform SeHCAT scanning at all in chronic diarrhea patients, partly due to a lack of availability, but also due to under-utilization in centers where SeHCAT testing is available.12

This issue is important, because chronic diarrhea is an extremely common complaint in the general population. In cross-sectional community-based surveys the prevalence is between 2% and 9%.13–17 A significant proportion of individuals reporting these symptoms will seek medical attention as a result,18 and in many the underlying cause could be bile acid malabsorption. In addition, in a recent meta-analysis more than 30% of patients meeting criteria for diarrhea-predominant irritable bowel syndrome (IBS-D) had an abnormal SeHCAT scan.19 These data suggest that type II bile acid malabsorption is the underlying, and potentially treatable, cause of symptoms in a significant proportion of individuals labeled as having either chronic functional diarrhea or IBS-D.

Greater awareness of the likely prevalence of bile acid malabsorption among chronic diarrhea patients undergoing SeHCAT scanning, as well as potential predictors of a positive test, and yield of scanning in those with symptoms compatible with IBS-D, may encourage more appropriate use of testing amongst Gastroenterologists. The aims of this study were to examine whether demand for SeHCAT scanning is increasing, which would suggest increased awareness of the condition, the yield of testing in patients with chronic diarrhea, factors that may predict a positive test, and characteristics of patients with bile acid malabsorption according to type and severity.

Materials and methods

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

Participants and setting

The study was a retrospective review of consecutive patients with chronic diarrhea referred for SeHCAT scanning at both the Leeds General Infirmary and St. James’s University Hospital in Leeds, West Yorkshire over a 7-year period. The hospitals provide secondary care services to a local population of almost 800 000 people in the North of England. Patients undergoing SeHCAT scanning as tertiary referrals from other hospitals outside the Leeds area were not eligible for inclusion in this study, in order to ensure that prevalence of bile acid malabsorption, and severity, among patients with chronic diarrhea were not overestimated, and that individuals recruited into the study were representative of the local secondary care population. With this in mind, it is important to stress that none of the clinicians whose patients were included in the study have a specialist interest in bile acid malabsorption. The relevant local research ethics committee in Leeds were approached, and confirmed that ethics approval was not required for a retrospective study such as this.

Data collection and synthesis

All subjects undergoing SeHCAT scanning between January 2005 and December 2011 were identified from data collected prospectively using the institutional radiology information system (CRIS, Healthcare Software Systems, Banbury, UK). Medical records of all individuals were reviewed retrospectively, including hospital notes, radiology results, and histopathology results. Data recorded included the date of the scan, the requesting clinician (physician or surgeon), the age of the patient at the time the scan took place, patient sex, and the percentage retention on the SeHCAT scan. A history of any of the following prior to the SeHCAT scan being requested was recorded: cholecystectomy [including indication, recorded as acute or chronic cholecystitis, gall bladder cancer, or gall bladder polyp(s)], terminal ileal Crohn’s disease, terminal ileal resection or right hemicolectomy for Crohn’s disease, terminal ileal resection or right hemicolectomy for reasons other than Crohn’s disease, acute enteric illness, radiotherapy, and evidence of biopsy-proven celiac disease or biopsy-proven microscopic colitis (collagenous colitis was defined as the presence of a subepithelial collagen band of ≥10 μm in thickness, and lymphocytic colitis was defined using a threshold of >20 intra-epithelial lymphocytes per 100 epithelial cells). Finally, symptoms reported by the patient at the time the SeHCAT scan was requested were extracted from the hospital notes, including abdominal pain or discomfort, and bloating. As all included patients had chronic diarrhea, the presence of abdominal pain or discomfort, in addition to diarrhea, was chosen as a surrogate measure of IBS-D, but only in patients with none of the above proposed risk factors for bile acid malabsorption, who would otherwise have been expected to have functional gastrointestinal symptoms.

Retention data were dichotomized into bile acid malabsorption present or absent, using a threshold of <5.0% retention to define severe, 5.0–9.9% to define moderate, and 10.0–14.9% to define mild bile acid malabsorption. Bile acid malabsorption was subclassified according to underlying cause, with type I defined as bile acid malabsorption in the presence of terminal ileal Crohn’s disease, terminal ileal resection or right hemicolectomy for Crohn’s disease, or terminal ileal resection or right hemicolectomy for other reasons, type III defined as bile acid malabsorption following cholecystectomy, acute enteric illness, radiotherapy, or in the presence of biopsy-proven celiac disease or microscopic colitis, and type II, or idiopathic, bile acid malabsorption in the absence of any of these potential etiologies.

Scanning protocol

All data were acquired on a Hawkeye Infinia™ dual-headed gamma camera (GE Healthcare, Chalfont St Giles, UK) using a standardized protocol. A 370 KBq capsule of SeHCAT was administered orally with a glass of water at day 1, followed by 10 min patient and background count acquisitions at 3 h and at 7 days, taking careful precautions to remove all radioactive sources from the vicinity of the camera room and ensure that patient positioning was consistent.

Statistical analysis

Time trends in the requesting of SeHCAT scanning over the 7-year study period were examined, in order to see whether the incidence of diagnostic testing for bile acid malabsorption was rising, which may indicate increasing awareness of the existence of the condition. The prevalence of bile acid malabsorption according to the various thresholds used to define its severity was reported, and the prevalence of each of the subtypes described above. Factors that predicted a positive test including age, sex, patient-reported symptoms (including presence of IBS-D), proposed etiologies (previous cholecystectomy, terminal ileal Crohn’s disease, terminal ileal resection or right hemicolectomy for Crohn’s disease, terminal ileal resection or right hemicolectomy for reasons other than Crohn’s disease, previous history of acute enteric illness or radiotherapy, and biopsy-proven celiac disease or microscopic colitis) were evaluated according to each of the severities and each of the subtypes of bile acid malabsorption.

Categorical demographic data were compared between those with and without bile acid malabsorption, and between each of the three severities and subtypes, using the chi-squared test. Mean age, along with a standard deviation (SD), was compared using either an independent samples t-test or one-way analysis of variance. Independent predictors of a positive test were determined by performing multivariate logistic regression analysis to control for all these data. Due to multiple comparisons a two-tailed P value of less than 0.01 was considered to be statistically significant for the latter analyses, and the results were expressed as odds ratios (OR) with 99% confidence intervals (CI). All statistical analyses were performed using SPSS for Windows version 14.0 (SPSS Inc, Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

There were 373 individuals with chronic diarrhea who had undergone SeHCAT scanning in either of the two hospitals between January 2005 and December 2011. The mean age of these individuals was 48.0 years (range 17–90 years), and 258 (69.2%) were female. Data were incomplete for some of the variables of interest, but only for three individuals.

The number of SeHCAT scans requested each year increased from 26 in 2005. By December 2011, the last time point considered by the study, 111 SeHCAT scans had been requested in the previous year, a more than four-fold increase. This increase in testing year-on-year was statistically significant (Spearman’s rank correlation coefficient = 0.87, P = 0.01). The proportion of individuals undergoing SeHCAT scanning with a positive test in each year did not vary significantly (Table 1, χ2 for trend = 1.46, P = 0.96).

Table 1.   Number of SeHCAT scans, and proportion of individuals testing positive, by year
YearNumber of individuals undergoing SeHCAT scanNumber of individuals with evidence of bile acid malabsorption (%) P value*
  1. *P value for Pearson chi-squared for trend.

20052614 (53.8)  
20063617 (47.2)  
20072615 (57.7)  
20083117 (54.8)  
20096330 (47.6)  
20108039 (48.8)  
201111158 (52.3)  
2005–2011373190 (50.9)0.96

Prevalence of, and risk factors for, bile acid malabsorption

There were 190 (50.9%) of 373 individuals with some degree of bile acid malabsorption following SeHCAT scanning. Of the 373 SeHCAT scans performed, 293 (78.6%) were requested by a Gastroenterologist, of which 145 (49.5%) were positive, and 80 (21.4%) by a Colorectal or Upper Gastrointestinal surgeon, of which 38 (47.5%) were positive (χ= 1.15, P = 0.28). Characteristics of individuals with any degree of bile acid malabsorption, compared with those without, are reported in Table 2. There were a significantly greater proportion of individuals with bile acid malabsorption who had undergone previous cholecystecomy (27.4%vs 13.3%, P = 0.003), terminal ileal resection or right hemicolectomy for Crohn’s disease (18.4%vs 1.6%, P < 0.001), or terminal ileal resection or right hemicolectomy for other reasons (7.4%vs 1.6%, P = 0.008).

Table 2.   Characteristics of individuals with bile acid malabsorption compared with those without
 All individuals tested (n = 373)No evidence of bile acid malabsorption (n = 183)Evidence of bile acid malabsorption (n = 190) P value*
  1. *P value for Pearson chi-squared for comparison of categorical data, and independent samples t-test for comparison of age. Denominators were 370, 180, and 190 respectively. Denominators were 370, 182, and 188 respectively. §Denominators were 370, 181 and 189 respectively.

Mean age (SD)48.0 (14.6)48.8 (14.8)47.3 (14.4)0.31
Female (%)258 (69.2%)128 (69.9)130 (68.4)0.75
Cholecystectomy (%)76 (20.5)24 (13.3)52 (27.4)0.003
Terminal ileal Crohn’s disease (%)17 (4.6)11 (6.0)6 (3.2)0.19
Terminal ileal resection or right hemicolectomy for Crohn’s disease (%)38 (10.2)3 (1.6)35 (18.4)<0.001
Terminal ileal resection or right hemicolectomy for other reasons (%)17 (4.6)3 (1.6)14 (7.4)0.008
History of acute enteric illness (%)22 (5.9)13 (7.1)9 (4.7)0.33
Previous radiotherapy (%)18 (4.8)11 (6.0)7 (3.7)0.30
Celiac disease (%)6 (1.6)5 (2.7)1 (0.5)0.09
Collagenous colitis (%)18 (4.9)12 (6.6)6 (3.2)0.13
Lymphocytic colitis (%)6 (1.6)3 (1.6)3 (1.6)0.97
Bloating (%)§74 (20.0)45 (24.9)29 (15.3)0.02
Abdominal pain or discomfort (%)§143 (38.3)79 (43.6)64 (33.9)0.05
Symptoms compatible with IBS-D (%)77 (20.6)56 (30.6)21 (11.1)<0.001

Among the 52 (68.4%) of 76 individuals who had undergone previous cholecystectomy with any degree of bile acid malabsorption, the indication for cholecystectomy was acute or chronic gallbladder inflammation in 29, and unclear in the remaining 23 patients. In total, 55 patients had undergone terminal ileal resection or right hemicolectomy for Crohn’s disease or other reasons, of whom 49 (89.1%) had evidence of bile acid malabsorption. Among 22 patients with a history of acute enteric illness, nine (40.9%) tested positive. Of the six patients with celiac disease tested, one (16.7%) had an abnormal SeHCAT scan, whilst among those with collagenous or lymphocytic colitis, six of 18 (33.3%) and three of six (50.0%) respectively had evidence of bile acid malabsorption. There were 168 (45.0%) of 373 individuals with no obvious risk factors for a positive SeHCAT scan, other than chronic diarrhea. Of these 168, 63 (37.5%) had some degree of bile acid malabsorption, with 18 (28.6%) of the 63 having severe bile acid malabsorption. A total of 77 patients reported symptoms compatible with IBS-D, and of these 21 (27.3%) tested positive. Significantly fewer individuals with bile acid malabsorption reported bloating (15.3%vs 24.9%, P = 0.02), or abdominal pain or discomfort (33.9%vs 43.6%, P = 0.05), and fewer met criteria for IBS-D (11.1%vs 30.6%, P < 0.001).

Following multivariate logistic regression previous cholecystectomy (OR 2.51; 99% CI 1.10–5.77), terminal ileal resection or right hemicolectomy for Crohn’s disease (OR 12.4; 99% CI 2.42–63.8), and terminal ileal resection or right hemicolectomy for other reasons (OR 7.94; 99% CI 1.02–61.6) remained significantly associated with the presence of any degree of bile acid malabsorption.

Prevalence of, and risk factors for, bile acid malabsorption according to severity

Overall, 50 (26.3%) of the 190 individuals with bile acid malabsorption had mild, 49 (25.8%) had moderate, and 91 (47.9%) had severe bile acid malabsorption. This equated to 13.4% of all 373 patients tested with mild, 13.1% with moderate, and 24.4% with severe bile acid malabsorption according to each of the thresholds we applied. Characteristics of individuals with bile acid malabsorption according to each of the three severities are reported in Table 3. There were significantly more patients with severe bile acid malabsorption with a previous terminal ileal resection or right hemicolectomy for Crohn’s disease (33.0%, P < 0.001), or terminal ileal resection or right hemicolectomy for other reasons (12.1%, P = 0.05). Bloating and abdominal pain or discomfort were more common in those with mild bile acid malabsorption (28.0%, P = 0.003 and 58.0%, P < 0.001 respectively), and a greater proportion of those with a mild degree of bile acid malabsorption fulfilled criteria for IBS-D, compared with those with moderate or severe bile acid malabsorption (30.0%vs 8.2% and 2.2%, P < 0.001). Of those with mild bile acid malabsorption, the majority had either type II (46.0%) or type III (48.0%), of those with moderate, most had type II (44.9%), whilst in the severe category the majority had type I bile acid malabsorption (48.4%).

Table 3.   Characteristics of individuals with mild, moderate, and severe bile acid malabsorption
 Mild bile acid malabsorption (n = 50)Moderate bile acid malabsorption (n = 49)Severe bile acid malabsorption (n = 91) P value*
  1. *P value for Pearson chi-squared for comparison of categorical data, and one-way analysis of variance for comparison of age, across the three groups. Denominators were 49, 49, and 90 respectively. ‡Denominators were 50, 48, and 91 respectively.

Mean age (SD)45.6 (13.5)50.0 (15.9)46.8 (13.9)0.28
Female (%)35 (70.0)36 (73.5)59 (64.8)0.56
Cholecystectomy (%)15 (30.0)16 (32.7)21 (23.1)0.43
Terminal ileal Crohn’s disease (%)0 (0)3 (6.1)3 (3.3)0.22
Terminal ileal resection or right hemicolectomy for Crohn’s disease (%)2 (4.0)3 (6.1)30 (33.0)<0.001
Terminal ileal resection or right hemicolectomy for other reasons (%)1 (2.0)2 (4.1)11 (12.1)0.05
History of acute enteric illness (%)4 (8.0)0 (0)5 (5.5)0.16
Previous radiotherapy (%)3 (6.0)2 (4.1)2 (2.2)0.51
Celiac disease (%)1 (2.0)0 (0)0 (0)0.25
Collagenous colitis (%)1 (2.0)3 (6.1)2 (2.2)0.40
Lymphocytic colitis (%)0 (0)0 (0)3 (3.3)0.19
Bloating (%)14 (28.0)9 (18.8)6 (6.6)0.003
Abdominal pain or discomfort (%)29 (58.0)16 (33.3)19 (20.9)<0.001
Symptoms compatible with IBS-D (%)15 (30.0)4 (8.2)2 (2.2)<0.001
Type of bile acid malabsorption (%)
Type I3 (6.0)8 (16.3)44 (48.4)<0.001
Type II23 (46.0)22 (44.9)18 (19.8) 
Type III24 (48.0)19 (38.8)29 (31.9) 

Prevalence of, and risk factors for, bile acid malabsorption according to subtype

Among the 190 patients with bile acid malabsorption, there were 55 (28.9%) patients with type I, 63 (33.2%) patients with type II, and 72 (37.9%) with type III bile acid malabsorption. Characteristics of individuals with bile acid malabsorption according to each of the three subtypes are reported in Table 4. Mean age was significantly lower in those with type I bile acid malabsorption (43.1 years, P = 0.02). Those with type II bile acid malabsorption were more likely to report bloating (27.4%, P = 0.003), and 33.3% met criteria for IBS-D. Finally, 80% of those patients with type I had a severe degree of bile acid malabsorption, compared with 28.6% and 40.3% in those with types II and III bile acid malabsorption respectively (P < 0.001).

Table 4.   Characteristics of individuals with types I, II, and III bile acid malabsorption
 Type I bile acid malabsorption (n = 55)Type II bile acid malabsorption (n = 63)Type III bile acid malabsorption (n = 72) P value*
  1. *P value for Pearson chi-squared for comparison of categorical data, and one-way analysis of variance for comparison of age, across the three groups.

  2. Denominators were 55, 62, and 72 respectively. Not applicable, Pearson chi-squared for comparison of categorical data not carried out, as categories were mutually exclusive.

Mean age (SD)43.1 (14.7)47.3 (13.8)50.5 (13.9)0.02
Female (%)33 (60.0)41 (65.1)55 (77.8)0.08
Bloating (%)3 (5.5)17 (27.4)9 (12.5)0.003
Abdominal pain or discomfort (%)13 (23.6)21 (33.9)30 (41.7)0.10
Symptoms compatible with IBS-D (%)0 (0)21 (33.3)0 (0)N/A
Severity of bile acid malabsorption (%)
Mild3 (5.5)23 (36.5)24 (33.3)<0.001
Moderate8 (14.5)22 (34.9)19 (26.4) 
Severe44 (80.0)18 (28.6)29 (40.3) 

Discussion

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

The demand for SeHCAT scanning increased significantly between 2005 and 2011. By 2011 the number of scans requested had increased more than four-fold compared with 2005. The proportion of individuals with a positive scan per year remained stable. In excess of 50% of patients undergoing SeHCAT scanning had some degree of bile acid malabsorption, and in almost 50% this was severe. More than 60% of those with a previous cholecystectomy, and almost 90% of those who had undergone terminal ileal resection or right hemicolectomy for any reason had bile acid malabsorption. Among this latter group, 80% had severe bile acid malabsorption. Even in those without any proposed risk factors, almost 40% tested positive on SeHCAT scanning. Whilst the prevalence of bloating, abdominal pain, and symptoms compatible with IBS-D were lower in those testing positive, these symptoms were significantly commoner among those with mild bile acid malabsorption, compared with moderate or severe. In addition, almost 30% of patients who reported symptoms compatible with IBS-D had an abnormal SeHCAT scan.

Strengths of this study include the fact that it was conducted using data from routine clinical practice, meaning the results are likely to be generalizable to physicians consulting with similar patients in secondary care. It is also one of the largest studies to examine yield of SeHCAT testing in patients with chronic diarrhea. In addition, due to the ability to access patients’ medical records, radiology and histopathology results, data were complete for nearly all individuals. This allowed examination of independent risk factors for bile acid malabsorption, as well as characterization of individuals according to type and severity, something which has not been done in any great detail previously. Limitations include the fact that, with the exception of SeHCAT results, data were not collected prospectively meaning that a symptom questionnaire was not administered to patients and validated diagnostic criteria, such as the Rome III criteria,20 were not able to be applied to ensure we had captured presence of individual gastrointestinal symptoms or IBS-D accurately, but instead we relied on the documentation of these symptoms in the patients’ medical records.

Other studies have examined the prevalence of bile acid malabsorption, using SeHCAT scanning in chronic diarrhea.6–10 In one of the largest studies to date, Borghede et al. reported data from 298 patients, 68% of whom tested positive.7 Similar to our data, 90% with a previous terminal ileal resection tested positive, but rates among those with a cholecystectomy or without any risk factors at all were higher than we observed, 86% and 60% respectively. In a Danish series of 135 patients with chronic diarrhea, 56% tested positive.8 A similar prevalence was reported in 166 patients undergoing SeHCAT testing in a UK district general hospital, with 51% testing positive.10 However, patient characteristics according to type or severity of bile acid malabsorption were not reported in these studies, and the relationship between symptoms and test results was not examined. Other studies have addressed the latter issue, including a series of 94 individuals, 45% of whom tested positive.9 Abdominal pain and bloating were no commoner in those with bile acid malabsorption. In one of the earliest reports, 60 of 181 patients with chronic diarrhea had a SeHCAT retention <15.0% at 7 days but, with the exception of presence of nocturnal diarrhea, symptoms did not seem to correlate with scan results.6

No definite association between previous acute enteric illness, celiac disease, or microscopic colitis and bile acid malabsorption were demonstrated, although this may relate to a lack of power due to the small number of individuals with these proposed etiologies. In a recent series of 135 patients with a positive SeHCAT scan, almost 20% were said to have a post-infective etiology, a far larger proportion than that observed in the present study.21 Among another 29 patients thought to have type II bile acid diarrhea, a clear history of acute gastroenteritis was elicited subsequently in 16.22 Previous studies examining the relationship between bile acid malabsorption and microscopic colitis are conflicting, with some suggesting no association,23,24 and others reporting a prevalence of a positive SeHCAT scan in individuals with collagenous or lymphocytic colitis of between 30% and 60%,25–27 in line with our findings.

The prevalence of symptoms compatible with IBS-D was lower in those with a positive SeHCAT scan compared with those with a negative scan. However, almost 30% of patients who reported symptoms compatible with IBS-D had an abnormal SeHCAT test using a threshold of <15.0% retention. In a series of 197 IBS-D patients in the UK who underwent SeHCAT scanning over 30% had bile acid malabsorption,28 and in a recent meta-analysis of 18 observational studies, containing 1223 patients, the prevalence of an abnormal SeHCAT scan was 10% at <5.0% retention, and 32.0% when <10.0% was used to define bile acid malabsorption.19 Given that individuals with IBS are more likely to undergo inappropriate cholecystectomy,29 part of this association may relate to subsequent type III bile acid malabsorption following surgery, but we excluded individuals with prior cholecystectomy, or any other organic risk factor for bile acid malabsorption, from the definition of IBS-D.

Predictors of a positive scan, other than prior surgery, were not elucidated. Despite the fact that surgical procedures, including terminal ileal resection, right hemicolectomy, and cholecystectomy were all strong predictors of a positive SeHCAT scan, almost 80% of scans were requested by physicians. This suggests that surgeons are either less aware of this condition, or that individuals with chronic diarrhea following any of these types of surgery are more likely to be referred to a Gastroenterologist for investigation.

One of the most striking findings was that over 40% of individuals undergoing SeHCAT scanning had none of the proposed risk factors for bile acid malabsorption, yet the yield of testing in these individuals was almost 40%. While this is lower than the prevalence observed among patients with previous cholecystectomy, or terminal ileal resection or right hemicolectomy, it is still considerable. In fact, overall, the second-largest proportion of those testing positive had idiopathic, or type II, bile acid malabsorption. In addition, despite the increase in demand for SeHCAT scanning year-on-year, the proportion of individuals testing positive remained remarkably constant, and the yield was therefore consistently high. Testing individuals with chronic diarrhea who have no other obvious risk factors for bile acid malabsorption routinely, via SeHCAT scan, therefore appears to be a worthwhile diagnostic strategy. Among those with chronic diarrhea and a previous terminal ileal resection or right hemicolectomy, almost 90% tested positive, and 80% had a severe degree of bile acid malabsorption. This suggests that a strategy of treating these individuals on suspicion with either colestyramine or colesevelam, with testing to confirm the diagnosis reserved for those who either fail to respond to, or do not tolerate, these agents may reduce the demand for SeHCAT scanning in this subgroup of patients.

In conclusion, bile acid malabsorption is a common diagnosis among patients presenting with chronic diarrhea. It should be considered as a potential cause in all patients, regardless of age, sex, symptoms, or proposed risk factors. The demand for SeHCAT scanning is rising locally, suggesting an increased awareness of bile acid malabsorption. This may have significant implications for the provision of services nationally, as chronic diarrhea is a common complaint, and up to 50% of these patients may have what is, essentially, a treatable condition yet access to scanning in many centers remains limited.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

We are grateful to Mr. Thomas Lee, Mr. Andrew Cook, and Mr. Ian Clegg, Advanced Practitioner Radiographers, Department of Nuclear Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK for performing the SeHCAT scans.

Disclosures

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

David J. Gracie: none. John S. Kane: none. Saqib Mumtaz: none. Andrew F. Scarsbrook: none. Fahmid U. Chowdury: none. Alexander C. Ford: has received speaker’s fees from GE Healthcare.

Author contribution

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References

DJG, JSK, SM, AFS, FUC and ACF conceived and drafted the study; DJG, JSK and SM collected all data. DJG and ACF analyzed and interpreted the data; ACF and DJG drafted the manuscript. All authors commented on drafts of the paper. All authors have approved the final draft of the manuscript.

References

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Funding
  8. Disclosures
  9. Author contribution
  10. References
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  • 2
    Fromm H, Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol 1986; 15: 56782.
  • 3
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