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Effects of Ileal Resection on Biliary Lipids and Bile Acid Composition In 1488 Gut, 1991,32, 1488-1491 Effects ofileal resection on biliary lipids and bile acid composition in patients with Crohn's disease Gut: first published as 10.1136/gut.32.12.1488 on 1 December 1991. Downloaded from A Lapidus, K Einarsson Abstract posed as an important factor in cholesterol gall Biliary lipid composition, cholesterol satura- stone formation.6 Since there is an increased tion, and bile acid pattern were determined in prevalence of gall stones among patients with fasting duodenal bile of 10 patients (four men Crohn's disease, particularly those with a history and six women, mean age 41 years) with ofileal resection, such patients might be expected Crohn's disease and a history ofileal resection to have a high degree ofcholesterol saturation.7"' (mean 64 cm). The data were compared with The aim of this study was to determine lipid corresponding values in a group of healthy composition, bile acid composition, and choles- subjects. None of the patients with Crohn's terol saturation in patients with Crohn's disease disease had supersaturated bile. Cholesterol who had previously undergone ileal resection of saturation was significantly lower in the various lengths to evaluate whether they have an patients with Crohn's disease than in the increased risk of developing cholesterol gall healthy subjects. The molar percentage of stones. cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile Methods acids were normal. Bile acid composition in the patients with ileal resection was charac- PATIENTS terised by a signficant decrease in the deoxy- Ten patients (four men and six women; mean age cholic acid fraction and a pronounced increase 41 years) with a history of ileal resection due to in the ursodeoxycholic acid fraction compared Crohn's disease were included in the study with the healthy subjects. The surprisingly (Table I). The length of resected ileum varied high percentage of ursodeoxycholic acid may from 20 to 160 cm with an average of 64 cm. contribute to the low degree of cholesterol None had clinical or laboratory evidence of saturation in bile. Based on these results active disease. All were of normal weight and http://gut.bmj.com/ patients with Crohn's disease should not have normolipidaemic. None had a history of gall an increased risk of cholesterol gail stone stone disease. All had normal liver and renal formation. function tests. One patient was treated with sulphasalazine while the other patients took no drugs that are known to interfere with lipid or Bile acids are formed in the liverfrom cholesterol. bile acid metabolism. are They excreted in bile and participate in the Informed consent to participate was obtained on September 25, 2021 by guest. Protected copyright. enterohepatic circulation as primary bile acids from each patient. The ethical aspects of the (chenodeoxycholic acid, cholic acid) and secon- study were approved by the Ethical Committee Division of Gastroenterology and dary bile acids (deoxycholic acid, lithocholic at Huddinge University Hospital. Hepatology, Department acid, ursodeoxycholic acid).'2 About 95-99% of of Medicine, Karolinska bile acids are reabsorbed from the intestine. This Institutet at Huddinge University Hospital, occurs mainly by an active process in the distal EXPERIMENTAL PROCEDURE Huddinge, Sweden part of the ileum and to a less extent by passive The patients were hospitalised for the study and A Lapidus diffusion along the whole intestine. fed the regular hospital diet containing about K Einarsson Ileal resection leads to bile acid malabsorption 0 5 mmol cholesterol per day. Bile was collected Correspondence to: Annika Lapidus, Department of and altered lipid composition.34 This might on the two following days. An oroduodenal tube Medicine, Huddinge result in 'bile acid deficiency' in the enterohepatic was introduced in the morning after an overnight University Hospital, S-141 86 Huddinge, Sweden. circulation and consequently a relative excess of fast. Gall bladder contraction was stimulated by Accepted for publication cholesterol and cholesterol supersaturated bile.' intravenous injection of cholecystokinin, and 11 February 1991 Cholesterol supersaturated bile has been pro- 5 ml of concentrated gall bladder bile was obtained through the tube. The tube was TABLE I Clinical data on the patients removed and the same procedure repeated the following day. Patient Age Weight Relative Serum cholesterol Serum triglycerides Ileum resection The lipid composition (cholesterol, phospho- No Sex (years) (kg) weight (%)* (mmolll) (mmol/l) (cm) lipids, and bile acids) and bile acid composition 1 M 39 76 103 5-2 1-1 20 of bile were determined. The satura- 2 M 57 72 95 3-9 0.7 30 cholesterol 3 M 22 62 80 2-5 10 50 tion was calculated. The results were compared 4 M 46 72 97 6-7 1-8 160 to data in a of 5 F 37 68 105 4-6 1-1 20 corresponding large group healthy 6 F 23 54 86 4.0 0.7 35 subjects previously reported." 7 F 61 54 95 3.0 1-4 50 8 F 22 58 94 3-6 1-5 70 9 F 65 65 114 4-9 1-1 100 10 F 37 50 74 2-4 1-2 105 BILIARY LIPID COMPOSITION AND CHOLESTEROL Mean 41 63 94 4-1 1-2 64 SATURATION *Calculated (body weight (kg)/height (cm)- 100) x 100%. For measurements of cholesterol and phospho- Effects ofileal resection on biliary lipids and bile acid composition in patients with Crohn's disease 1489 lipids a portion of the duodenal bile was im- TABLE II Biliary lipid composition and cholesterol saturation mediately extracted with 20 volumes of chloro- (mean (SEM)) form-methanol 2:1 (vol/vol). Cholesterol was Healthy Gut: first published as 10.1136/gut.32.12.1488 on 1 December 1991. Downloaded from determined by an enzymatic method'2 and phos- Patients subjects* pholipids by the method of Rouser et al.'3 The (n =10) (n = 60) Significance total bile acid concentration was determined Cholesterol (molar %) 4-6 (0.5) 5 6 (0.3) NS Phospholipids (molar %) 22.4 (1.2) 20.6 (0.5) NS using a 3-ct-hydroxysteroid dehydrogenase Bile acids (molar %) 73.0 (1-7) 73-6 (0.6) NS assay. 14 Cholesterol saturation was calculated Cholesterol saturation (%) 64 (6)t 86 (3) p<0005 according to Carey's method with the total lipid *Data from Einarsson et al." concentration assumed to be 10 g/100 ml in NS=not significant. concentrated fasting duodenal bile. '` Cholesterol t67 (6)% after calculation with a correction factor for saturation was also calculated with a correction ursodeoxycholic acid rich bile.' factor for ursodeoxycholic acid rich bile.'5 TABLE III Biliary bile acid composition (mean (SEM)) Healthy BILIARY BILE ACID COMPOSITION Patients subjects* The duodenal bile samples were hydrolysed with (n= 10) (n=SO) Significance 1 mol/l potassium hydroxide in closed steel tubes Cholicacid(%) 38-8(3.9) 41 2(1.5) NS 1 The bile Chenodeoxycholic acid (%) 37-2 (2.3) 34.5 (1.2) NS for 12 hours at 10°C. deconjugated Deoxycholic acid(%) 12 7 (5.7) 23-4 (1.8) p<005 acids were extracted with ethyl ether after acidi- Lithocholicacid((%) 1.1(0.8) 0.7(0.4) NS fication with 6 mol/l HCI to pH 1. An aliquot of Ursodeoxycholic acid (%) 10.3 (2-8) 0.7 (0.3) p<0001 the deconjugated bile acids was methylated, *Data from Einarsson et al." trimethylsilylated, and analysed by gas-liquid NS=not significant. chromatography using a 1% HiEff BP8 column as described previously. 16 Crohn's disease have a low molar percentage of cholesterol saturation of bile. STATISTICAL ANALYSIS cholesterol and low Data are presented as mean (SEM). Compari- No correlation between cholesterol saturation sons ofdata between patients andhealthy subjects and length of resected ileum was found. Various were calculated by using Student's t test. Prob- data on bile lithogenicity in patients with values <0 05 were considered to be Crohn's disease have been published. Most ability studies have reported on a high frequency of significant. cholesterol supersaturated bile in Crohn's disease patients with ileal resection or ileal Results dysfunction.5 7-'9 Only Farkkila has reported http://gut.bmj.com/ Data for biliary lipid composition and cholesterol that patients who had undergone ileal resection saturation are given in Table II. The molar had low to normal cholesterol saturation of bile."0 percentage of cholesterol was lower, but not Farkkila found that the molar percentage of significantly lower, in the patients with ileal biliary cholesterol was inversely correlated with resection than in the healthy control subjects faecal bile acid excretion in patients with ileal (4.6 molar % v 5.6 molar % p<0 1). There were resection and suggested that biliary cholesterol no significant differences in the molar percen- secretion decreases with increasing loss of bile on September 25, 2021 by guest. Protected copyright. tages of phospholipids or bile acids between the patients and the healthy subjects. Cholesterol saturation was significantly lower * Healthy in the patients than in the control subjects (64% v a Crohn's disease 86%, p<0 005). None of the 10 patients had supersaturated bile. As cholesterol saturation of 160- bile increases with age," we related the data for our patients to the data for control subjects of 140- corresponding age. As the Figure shows, in all but one cholesterol saturation of bile was C patient 120 - below normal. 0 Biliary bile acid composition differed between (U 100- the patients and the control subjects (Table III). a Thus the percentage of deoxycholic acid was -c significantly lower in the patients than in the a1) 80- control subjects (12.7% v 23.4% p<0 05).
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