90 Gut 1994; 35:90-93 Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT Gut: first published as 10.1136/gut.35.1.90 on 1 January 1994. Downloaded from H Nyhlin, M V Merrick, M A Eastwood Abstract theless, some authors have reported a high Patients with Crohn's disease who suffer from prevalence.45 longstanding diarrhoea that does not respond Conventional methods of diagnosing diseases to conventional treatment pose a common of the terminal ileum lack either sensitivity or clinical problem. Bile acid malabsorption is a specificity, or both. Radiological studies give no possible cause, although its prevalence and information about functional status, while the clinical importance is unclear. This paper Schilling test is influenced by factors not con- explores the clinical indications for referring nected with terminal ileal function, such as patients with Crohn's disease for bile acid bacterial colonisation and pernicious anaemia. assessment and the extent of bile acid mal- The cholyl-glycine-l-14C breath test measures absorption in this selected group of patients. terminal ileal function but is also influenced by The selenium labelled bile acid SeHCAT was bacterial contamination of the small bowel, the used to assess the effect of disease on the latter being the principal indication for perform- integrity of the enterohepatic circulation. ing this test. Direct measurement of faecal bile Altogether 76% ofthe patients referred for bile acids or of faecally excreted14C-labelled conju- acid assessment had longstanding diarrhoea gated bile acids are sensitive tests giving accurate that had not responded to conventional anti- measurements of the functional condition of the diarrhoeal treatment or an increase in steroid terminal ileum, but they are laborious, rely on therapy as their sole or predominant symptom. faecal collections, and are not easily performed in Ninety per cent of patients with bowel resec- patients with diarrhoea. The introduction of a tions, almost exclusively ileocaecal, had selenium labelled bile acid - SeHCAT67 - pro- abnormal SeHCAT retention (<5% at seven vided a simple and reliable method of studying days). Twenty eight per cent of patients with the enterohepatic circulation and the effect of Crohn's disease who had not undergone resec- diseases on its integrity. We report here our tion 28% had a SeHCAT retention <5%, conclusions concerning its role in the clinical http://gut.bmj.com/ signifying bile acid malabsorption. Nineteen of management of patients with Crohn's disease, 22 patients given cholestyramine treatment after six years experience. subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the pre- valence of bile acid malabsorption in this Patients and methods selected group with Crohn's disease is suffici- Between 1983 and 1989 53 patients with Crohn's ently high to justify performing the SeHCAT disease from two hospitals in Edinburgh that on September 28, 2021 by guest. Protected copyright. test in order to separate the various differential have specialist gastrointestinal facilities were diagnoses. investigated for bile acid malabsorption using (Gut 1994; 35: 90-93) SeHCAT. This test was not routinely available before 1983. There was no agreed protocol and patients were investigated only to the extent Chronic or intermittent diarrhoea in adults may considered clinically appropriate by the clinician be an expression of various intestinal infections, concerned. SeHCAT retention was measured inflammatory bowel disease, malabsorption, or only after other investigations had failed to functional disorders of the gastrointestinal account adequately for their refractory diar- system. Aqueous concentration of bile acids in rhoea. Patients who had been referred for the colon greater than 3 mM, especially of SeHCAT retention measurement were identified chenodeoxycholic or deoxycholic acids, whether from the records of the Department of Nuclear due to disease, after resection of the terminal Medicine and their notes were reviewed in 1990 ileum, or idiopathic, may produce diarrhoea' as a by an independent physician (HN). Clinical consequence of a number of factors operat- details before and after investigation were avail- ing synergistically. These include increased able in all but two of the patients, allowing for Gastro-Intestinal Unit epithelial permeability resulting from a deter- assessment ofthe reasons for investigation, local- and Department of gent effect, stimulation of cyclic adenosine isation of disease, and the implications of the Nuclear Medicine, monophosphate (cAMP) in the colonic mucosa, SeHCAT results for treatment. Western General Hospital, Edinburgh nervous mechanisms, and/or increased colonic Twenty five of the patients had unoperated H Nyhlin motility. The effect is exacerbated in the Crohn's disease and their symptoms had failed to M V Merrick presence of pronounced steatorrhoea by certain respond adequately to conventional treatment. M A Eastwood metabolites of fatty acids produced by colonic The distribution of disease is shown in Table I. Correspondence to: Dr M A Eastwood, bacteria. The prevalence and clinical importance Twenty six had previously undergone bowel Gastro-Intestinal Unit, of bile acid malabsorption in Crohn's disease is resection for their Crohn's disease (22 ileocaecal, Western General Hospital, Edinburgh EH4 2XU unclear. It is usual after resection of the terminal three colonic, and one limited ileal resection. Accepted for publication ileum, but according to some reports occurs in Thirty one were female (mean age 39-8 years, 12 May 1993 only a minority of unoperated patients.2 3 Never- range 16-72 years) and 20 male (mean age 37-9 Bile acid malabsorption in Crohn's disease and indicationsfor its assessment usingSeHCA T 91 years, range 16-60 years). The mean duration of TABLE II Localisation in relation to SeHCAT retention disease was 9-6 years (range 1-31 years). Localisation After resection SeHCAT retention seven days after oral without was measured using a shadow- Small radiological Gut: first published as 10.1136/gut.35.1.90 on 1 January 1994. Downloaded from administration intestinal Small signs of shield, whole body gamma counter, as pre- SeHCAT +colonic intestinal Colonic recurrence viously described.8 Patients attended in the retention (n=9) (n= 15) (n= 14) (n = 13) morning, having fasted overnight. After <5% 5 12 1 12 measurement of their background radioactivity 5-10% 1 - 2 1 levels (principally to ensure that they had not >10% 3 3 11 received other radioactive tracers), 40 kBq of 58CoB12 was administered orally with a drink of water. Thirty minutes later the patient's radio- TABLE III SeHCAT results in relation to reasonfor activity level was counted again to obtain the investigation (all patients) 100% count rate value and also an estimate ofthe Diarrhoea+ scattered counts from the cobalt in the selenium SeHCAT Diarrhoea extension of Diarrhoea+ window. A total of 40 kBq of 75SeHCAT was retention only disease miscellaneous then administered orally, and after a further wait <5% 25 1 4 of half an hour, a second measurement was 5-10% 3 - 1 made. The contribution of the scatter from 58Co >10% 11 6 4 in the 75Se window was calculated and sub- tracted. The patients returned one week later, measurement was made of the when a further TABLE IV Outcome ofSeHCAT in Crohn's disease patients radioactivity in both selenium and cobalt with and without bowel resection windows. The retention ofeach was expressed as a percentage of the initial administered activity. Bowel resection No resection The in vivo stability of both SeHCAT9 and SeHCAT retention (n=26) (n=25) are well established. Phanton measure- <5% 23 7 58CoB12 5-10% 3 1 ments in our department indicate that the tech- > 10% 3 17 nique has a precision ofbetter than +005% and a sensitivity of better than 1% of the administered activity. TABLE V Cholestyramine, effectiveness on symptoms in relation to SeHCAT results Results SeHCAT retention Effective Not effective The most common indication for investigation http://gut.bmj.com/ <5% 18 1 (Table I) was the presence of diarrhoea that had 5-10% - 2 failed to respond to conventional treatment and >10% 1 - for which no adequate diagnosis had been made. Thirty one ofthe 51 patients (76%) had diarrhoea as their predominant or only symptom and in most cases it was of lengthy duration (greater SeHCAT retention of less than 5%; he also had than three months) and had not responded to ileal strictures on barium follow through. Nine on September 28, 2021 by guest. Protected copyright. conventional antidiarrhoeal treatment or to an patients who had severe symptoms in addition to increase in steroid therapy. SeHCAT retention their diarrhoea were referred for investigation of was less than 5% at seven days in 25 of these suspected bile acid malabsorption, including two patients (64%) and between 5% and 10% in three whose predominating symptom was flatulence. others (Tables II and III). In a further seven Both the latter two patients had SeHCAT reten- patients the diarrhoea had been controlled to tion of less than 5% at seven days and responded some extent by treatment, but there was a symptomatically to cholestyramine. suspicion that involvement ofthe terminal ileum Table IV summarises the SeHCAT results in was causing bile acid malabsorption and diar- relation to bowel resection. Twenty three of the rhoea. Four of these patients had a normal 26 patients (90%) with bowel resection had a barium follow through, in