Biliary lipid composition in patients with nonoperated Crohn's disease

Lipid composition of fasting duodenal bile was studied in 56 patients with nonoperated Crohn's disease, 21 normals matched for age and sex, 13 patients with cholesterol cholelithiasis, and 9 patients with ileal resections. Crohn's patients had a significantly higher mean saturation index, calculated according to Thomas (0.84±0.51) when compared to normal (0.63±0.25). Patients with ileocolonic Crohn's disease and patients with severe bile acid malabsorption, particularly, showed an increased incidence of cholesterol saturated bile. Saturation in patients with nonoperated Crohn's disease was not increased to the levels found in patients with ileal resection or cholesterol gallstones. Bile acid composition of gallbladder bile was characterized by a significant decrease of thedeoxycholate fractions in patients with Crohn's ileocolitis and colitis as well as in ileal resected patients. These qualitative changes of bile acid composition may influence cholesterol solubility. It is concluded that patients with nonoperated Crohn's disease may have an increased risk of developing cholesterol gallstones.     

Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn''s disease.

Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn's disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn's disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn's disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn's disease should not have an increased risk of cholesterol gall stone formation.     

The composition of hepatic and gallbladder bile in patients with gallstones

Bile specimens were obtained from 17 patients with gallstones and 21 patients with duodenal ulcer. The specimens were obtained from the former by needle aspiration of the gallbladder and common bile duct at operation and from the latter by duodenal intubation. The concentrations of bile salt, phospholipid, and cholesterol were measured. Gallbladder bile from gallstone patients contained significantly more cholesterol than did ;duodenal' bile from duodenal ulcer patients. Hepatic bile from gallstone patients contained significantly more cholesterol than did gallbladder bile from the same patients. When the data were plotted on triangular coordinates the relative composition lay within the zone of cholesterol solubility in all 21 ulcer patients. The relative composition of hepatic bile lay outside the zone of cholesterol solubility in five gallstone patients, at the limits of cholesterol solubility in a further three, and within the micellar zone in the remaining nine patients. This suggests that supersaturation of hepatic bile with cholesterol is not the sine qua non for the production of cholesterol gallstones.     

Bile-rich duodenal fluid as an indicator of biliary lipid composition and its applicability to detection of lithogenic bile

A comparison was made of the lipid composition of duodenal and gallbladder bile in 10 patients with cholesterol gallstones and in 11 patients without. The lipid composition of duodenal and gallbladder bile was found to be similar in each patient. A phase diagram plot of the biliary lipid composition data showed that duodenal bile is also a valid indicator of the presence or absence of lithogenic bile. Also, based on the analysis of the duodenal lipids, a distinction could be made between the presence of calcium bilirubinate and that of cholesterol gallstones. Analysis of the lipids of duodenal bile should serve as a useful tool in studying the effect of various agents and factors on the metabolism of the biliary lipids.Supported in part by USPHS Research Grant-in-Aid 1RO1-AM-14668-01 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health.     

The effect of the site of lesion and extent of resection on duodenal bile acid concentration and vitamin B12 absorption in Crohn's disease.

Duodenal bile acid concentration following a standard meal, glycine/taurine (G/T) ratio, vitamin B12 absorption, and faecal fat were determined in 79 patients with Crohn's disease. Intestinal resection had been made in 50 patients before the study, and no evidence of recurrence was present at the time of the study. Among 46 patients subjected to ileal resection of 10-180 cm, a reduced duodenal bile acid concentration and vitamin B12 malabsorption was almost invariably present when 50 cm or more of ileum had been removed. Patients with smaller resections and unoperated patients did not show a consistent pattern. Vitamin B12 absorption and duodenal bile acids were of equal value as indicators of ileal dysfunction with the exception that, in 10 ileostomy patients, duodenal bile acids were decreased in every case, but vitamin B12 absorption only when 80 cm of ileum or more had been resected. G/T-ratio was related to the extent of ileal resection-being elevated after large resections (80 cm or more)-but not to the presence of an abnormal flora. Faecal fat was much more elevated in ileostomy patients with large ileal resection (80 cm or more) than in unoperated patients and patients without an ileostomy.     

Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile

BACKGROUND & AIMS: The role of the gallbladder in gallstone pathogenesis is still unclear. We examined the effects of gallbladder mucosal lipid absorption on lipid composition and cholesterol crystallization in bile. METHODS: The in vitro-isolated, intra-arterially perfused gallbladder model was used (1) to compare the absorption rates of lipids from standard bile by gallbladders obtained from 7 patients with cholesterol gallstones and 6 controls; and (2) to measure the microscopic cholesterol crystal detection time in cholesterol-enriched pig bile before and after lipid absorption by the pig gallbladder. RESULTS: Control gallbladders, but not cholesterol gallstone gallbladders, significantly reduced cholesterol (P < 0.02) and phospholipid (P < 0.01) and increased bile salt (P < 0.01) molar percentages in bile over a 5-hour period by efficient and selective cholesterol and phospholipid absorption. A histomorphometric study of the epithelial cells showed significantly higher values for nuclear density (P < 0.01) and nuclear (P < 0.05) and cytoplasmic (P < 0.05) areas in the cholesterol gallstone than the control group. Sequential microscopy of cholesterol-enriched pig bile showed significantly shorter cholesterol filament (P < 0.01) and typical cholesterol plate (P < 0. 02) detection times before than after exposure of bile to the gallbladder lipid absorption. CONCLUSIONS: In cholesterol gallstone disease, the human gallbladder epithelium loses its capacity to selectively and efficiently absorb cholesterol and phospholipids from bile, even if it is hyperplastic and hypertrophic. This epithelial dysfunction eliminates the positive effect that the normal gallbladder exerts on cholesterol solubility in bile and might be a pathogenetic cofactor for cholesterol gallstone formation.     

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.     

Plasma lathosterol and campesterol in detection of ileal dysfunction

Plasma lathosterol levels reflect cholesterol synthesis, especially that induced by bile acid malabsorption, whereas plasma plant sterol contents change in parallel with cholesterol and fat absorption. The significance of lathosterols and plant sterols (campesterol and sitosterol) was therefore studied in detection of ileal dysfunction in 29 patients with ileal resection (7 with no malabsorption, 8 with only bile acid malabsorption, and 15 with bile acid, fat, and cholesterol malabsorption) and in 8 jejunoileal bypass patients with fat, bile acid, and cholesterol malabsorption. Ileal dysfunction-induced faecal loss of bile acids was proportionate to cholesterol synthesis, which, in turn, was proportionate to the plasma levels of lathosterols, so that the lathosterols contents were also closely correlated (r = 0.880) to faecal bile acids. The lower the cholesterol absorption, the lower was the plasma campesterol (less consistently, beta-sitosterol) level and the higher the faecal fat. Thus, elevated plasma lathosterol content is highly suggestive of bile acid malabsorption in a patient with suspected ileal dysfunction. High plasma content of lathosterols combined with a low campesterol level points to associated fat malabsorption, indicating that the lathosterol to campesterol ratio in plasma is frequently increased in patients with ileal dysfunction associated with steatorrhoea.     

Ileal resection/dysfunction in childhood predisposes to lithogenic bile only after puberty.

Children with ileal resection/dysfunction since infancy have bile that is not supersaturated with cholesterol. Five sexually mature subjects (age 16-19 years) who had been previously investigated in childhood (age 4-9 years) were studied. Gallstones were found in one. Bile rich duodenal aspirates were analyzed for lipid content (molar fraction) and the cholesterol saturation index was calculated. In the postpubertal subjects, a significantly higher proportion of biliary cholesterol (22.0% +/- 4.8% vs. 3.2% +/- 0.6% and 5.7% +/- 0.5%, P less than 0.005) and significantly lower bile acids (58.1% +/- 3.9% vs. 79.7% +/- 2.3% and 78.2% +/- 1.9%, P less than 0.005) were found compared with the initial (prepubertal) samples or in samples from 20 healthy young adults. The cholesterol saturation index was significantly higher (3.1 +/- 0.7 vs. 0.6 +/- 0.1 and 1.1 +/- 0.1, P less than 0.005) whereas phospholipid content did not change (19.9% +/- 1.6% vs. 17.1% +/- 1.8% and 16.6% +/- 1.6%) as compared with themselves before puberty and as healthy young adults, respectively. It was concluded that children with ileal resection/dysfunction do not appear at risk for cholesterol cholelithiasis before puberty; however, the development of biliary cholesterol supersaturation after puberty may predispose them to gallstone formation in adulthood.     

Effects of colectomy on bile composition, cholesterol saturation and cholesterol crystal formation in humans

Total or subtotal colectomy is the surgical treatment of choice for patients with ulcerative colitis. Recently it has been reported that colectomy may lead to increased lithogenicity of bile, short nucleation time, cholesterol crystal formation, and gallstone disease. We examined whether colectomy in patients with ulcerative colitis leads to changes in bile composition that predisposes to cholesterol crystal formation and cholesterol gallstone disease. Ten consecutive patients who had previously undergone ileostomy and colectomy because of ulcerative colitis were admitted for ileal pouch surgery. At operation bile was obtained by puncture of the gallbladder. Controls were 35 patients undergoing cholecystectomy (23 for cholesterol gallstone disease and 12 for reasons other than gallstone disease). The gallbladder bile was analyzed for cholesterol crystals, bile acid, and biliary lipid composition, cholesterol saturation, and nucleation time. The colectomized patients had normal biliary lipid composition, normal cholesterol saturation, and normal nucleation time, in contrast to gallstone patients who displayed highly supersaturated bile with a short nucleation time. Thus patients with ileostomy after colectomy because of ulcerative colitis have normal cholesterol saturation and nucleation time of bile.     

Duodenal bile examination in identifying potential non-responders to bile salt treatment and its comparison with gall bladder bile examination.

The results of bile salt treatment in patients with radiolucent stones and a functioning gall bladder have been poor. In 42 of these patients awaiting cholecystectomy we determined the value of duodenal bile examination in predicting gall stone composition, and thus identifying those less likely to respond to bile salt therapy. Based on chemical analysis and scanning electron microscopy, 28 of 42 (67%) gall stones retrieved at surgery were potentially insoluble. Microscopic examination of duodenal bile correctly identified 21 (75%) of them: it predicted all four (100%) pigment stones, three of six (50%) calcium carbonate containing cholesterol stones, and 14 of 18 (78%) cholesterol stones with pigment shells. It was nearly as reliable as microscopic examination of bile aspirated directly from the gall bladder during surgery (21 (75%) v 23 (82%); p = NS). Furthermore, the presence of cholesterol crystals in duodenal bile was a more sensitive indicator than chemical detection of supersaturation (34 of 38 (89%) v 25 of 35 (71%); p < 0.05) for prediction of cholesterol gall stones. Microscopic examination of duodenal bile, if used as a screening test, could help to exclude potential non-responders and thereby improve considerably the results of oral bile salt treatment for gall stone dissolution.     

Ursodeoxycholic acid ingestion after ileal resection

The effect of ursodeoxycholic acid ingestion on biliary bile acids and biliary lipids was studied in six patients after ileal resection. All patients had bile acid malabsorption, as documented by increased breath and fecal excretion of¹⁴C after oral administration of [1-¹⁴C] cholylglycine. Fasting duodenal bile was collected by intubation before and seven days after ursodeoxycholic acid administration (4 g/day), and biliary bile acid and lipid composition were determined. Ursodeoxycholic acid ingestion increased the percentage of ursodeoxycholic acid in bile tenfold (3.6±2.6% vs 38.6±12.0%) and decreased chenodeoxycholic acid in bile by approximately 40%. Before ursodeoxycholic acid ingestion, bile was supersaturated in all patients. After ursodeoxycholic acid ingestion, cholesterol saturation decreased in all six patients by an average of 43%, and bile became unsaturated in five. Ursodeoxycholic acid ingestion had no effect on stool frequency. We conclude that, as in subjects with an intact enterohepatic circulation, ursodeoxycholic acid therapy has litholytic potential in patients after ileal resection.This work was supported by NIH Grants AM 15887 and RR 585 and by the Mayo Foundation. Part of this work was reported at the 1979 meeting of the American Gastroenterological Association and published in abstract form.At the time this work was done, Dr. LaRusso was a Teaching and Research Scholar of the American College of Physicians.     

Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility

The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation.     

The effect of sodium oleate on cholesterol solubility in bile salt-lecithin model systems

Reflux of pancreatic secretions and bacterial infection have been suggested as important factors in gallstone formation in some instances by introducing into bile phospholipases hydrolyzing lecithin to lysolecithin, mono- and diglycerides, and free fatty acids. Since there is little data on free fatty acids, we studied the effect of sodium oleate, the soap of one of the major fatty acid derivatives of lecithin, on cholesterol solubility in unconjugated bile salt-lecithin model solutions to see if an increase in this component might lead to saturation of bile with cholesterol. In the absence of lecithin, sodium oleate decreased cholesterol solubility in bile salt solutions at concentrations physiologic for bile, although cholesterol solubility was increased by oleate at higher oleate-bile salt ratios. In the presence of lecithin, sodium oleate decreased cholesterol solubility at all concentrations studied. Significant differences in cholesterol solubility were found for all comparable concentrations of sodium cholate and deoxycholate studied, both in the presence and absence of lecithin. Our studies showed that an increase in free fatty acid concentration can increase cholesterol saturation significantly in unconjugated bile salt-lecithin model solutions. Whether or not free fatty acid concentrations in pathologic bile reach levels sufficient to contribute to cholesterol saturation and gallstone formation cannot be determined until more adequate data on the minor lipid composition of bile becomes available.Supported by Research Grant AM-09368 and Training Grant T1-AM-05314 from the National Institute of Arthritis and Metabolic Diseases U.S. Department of Health, Education and Welfare.     

Gallbladder bile composition in patients with Crohn＇s disease

AIM:To further elucidate the pathogenesis andmechanisms of the high risk of gallstone formation inCrohn's disease.METHODS:Gallbladder bile was obtained from patientswith Crohn's disease who were admitted for electivesurgery (17 with ileal/ileocolonic disease and 7 withCrohn's colitis).Fourteen gallstone patients servedas controls.Duodenal bile was obtained from tenhealthy subjects before and after the treatment withursodeoxycholic acid.Bile was analyzed for biliary lipids,bile acids,bilirubin,crystals,and crystal detection time(CDT).Cholesterol saturation index was calculated.RESULTS:The biliary concentration of bilirubin wasabout 50% higher in patients with Crohn's disease thanin patients with cholesterol gallstones.Ten of the patientswith Crohn's disease involving ileum and three of thosewith Crohn's colitis had cholesterol saturated bile.Fourpatients with ileal disease and one of those with colonicdisease displayed cholesterol crystals in their bile.About1/3 of the patients with Crohn's disease had a shortCDT.Treatment of healthy subjects with ursodeoxycholicacid did not increase the concentration of bilirubin induodenal bile.Several patients with Crohn's disease,with or without ileal resection/disease had gallbladderbile supersaturated with cholesterol and short CDT andcontained cholesterol crystals.The biliary concentrationof bilirubin was also increased in patients with Crohn'scolitis probably not due to bile acid malabsorption.CONCLUSION:Several factors may be of importance forthe high risk of developing gallstones of both cholesteroland pigment types in patients with Crohn's disease.     

The partial ileal bypass operation does not cause essential fatty acid deficiency

Recent studies have indicated that ileal resection may lead to essential fatty acid deficiency, as demonstrated by plasma fatty acid composition. In the present study the serum cholesterol ester fatty acid composition was determined in patients who had undergone a partial ileal bypass operation several years earlier. The mean length of ileal exclusion was 2.0 m (range, 1.4-2.5 m). The patients with ileal bypass had severe bile acid malabsorption and slight fat malabsorption (fecal fat, 16 g/day). The fatty acid composition of serum cholesterol esters in the patients with ileal exclusion was identical with that of matched controls; for example, linoleic acid comprised 58% of the C14-18 fatty acids in the control patients and 61% in the patients with ileal bypass. It is concluded that exclusion of the distal third of a healthy small bowel does not cause essential fatty acid deficiency.     

The cholesterol saturation index of human bile

A line of maximum cholesterol solubility was obtained by plotting the ratios of bile salt to cholesterolversus bile salt to phospholipid from model solutions simulating bile containing human biliary lecithin, human bile salts, and cholesterol. The sole factor responsible for the solubility of cholesterol (above the 3% total solid content) was found to be the proportion of bile salts to lecithin. This relationship could be expressed mathematically by a polynomial equation and the bile-salt-to-cholesterol ratio at maximum cholesterol holding capacity for a bile ascertained. From this information the percent cholesterol saturation of human bile could be determined. This method was applied to the bile obtained from 139 patients. The biles from 49 of 53 patients with known cholesterol gallstones had a cholesterol saturation index of 100% or greater, while 53 of 77 patients without evidence of cholesterol gallstones had a cholesterol-unsaturated bile. This method quantitates the exact degree of cholesterol saturation in human bile (cholesterol saturation index-CSI), and the availability of this index should be useful for diagnostic and therapeutic purposes.Supported in part by United States Public Health Service Research Grant 1R01-AM-14668-02 from the National Institute of Arthritis and Metabolic Disease, National Institutes of Health, United States Public Health Service.     

Rapid cholesterol nucleation time and cholesterol gall stone formation after subtotal or total colectomy in humans.

Changes in biliary lipid composition, pH, ionised calcium, total and unconjugated bilirubin, and cholesterol nucleation time of gall bladder bile samples were examined in six patients who had undergone subtotal or total colectomy between five months and seven years previously, and values were compared with those in control patients with no gall stones. The colectomy group mainly comprised patients with ulcerative colitis and familial adenomatosis coli, in whom only a short length of the terminal ileum (mean (SEM) 2.25 (0.57) cm) had been resected. The reconstruction procedures were ileoanal anastomosis in two patients, terminal ileostomy in two, ileorectal anastomosis in one, and J shaped ileal pouch-anal anastomosis in one patient. The distributions of age, sex, and relative body weight were similar in the two groups. The gall bladder bile was lithogenic in the post colectomy group--these patients had a significantly increased cholesterol saturation index (p < 0.01) and rapid cholesterol nucleation time (p < 0.05) compared with the control group. A significant increase in the molar percentage of cholesterol and a decrease in that of total bile acid associated with significantly decreased secondary bile acids (p < 0.05) were observed in the post colectomy group. Gall stones formed in two of six patients after colectomy were cholesterol stones containing more than 80% cholesterol by dry weight. Total and unconjugated bilirubin, pH, and ionised calcium values were similar in the two groups. The results indicate that after total or subtotal colectomy the composition of gall bladder bile increases the risk of cholesterol gall stone formation.     

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.     

Gallbladder function, cholesterol stones, and bile composition.

Gallbladder bile obtained at operation from five patients with no symptoms of biliary disease was undersaturated with cholesterol in every case. However, gallbladder bile from patients with stones composed of 97-100% crystalline cholesterol was on average just saturated with cholesterol when the gallbladder was functioning and undersaturated when it was not. Regardless of gallbladder function, the patients with stones had on average significantly more cholesterol in their bile than in the control group, but the differences between the mean composition of bile from functioning and non-functioning gallbladders were not significant. Common duct bile from patients with non-functioning and functioning gallbladders was on average supersaturated with cholesterol, but there was significantly more bile salt and significantly less cholesterol in the bile from patients with non-functioning gallbladders. Only in the case of patients with functioning gallbladders did the mean composition of the common duct and gallbladder biles differ significantly. The former contained significantly more cholesterol and less bile salt than the latter. It is suggested that patients with non-functioning gallbladders may be 'autocholecystectomised' with the duct bile reverting to a more 'normal' composition.