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Isolation and identification of bile salts conjugated with cysteinolic acid from bile of the red seabream, Pagrosomus major.

Bile salts present in gallbladder of wild and cultured red seabream, Pagrosomus major, a marine teleost were analyzed. The bile from wild red seabream was found to contain two previously unknown bile salts along with two known bile salts, taurocholate and taurochenodeoxycholate. Isolation of each bile salt was performed by column chromatography. Fast atom bombardment mass spectra of the unknown bile salts showed the molecular ions (M-H)- of m/z 544 and 528 which are shifted 30 mass units upfield compared to those (m/z 514 and 498) of taurocholate and taurochendeoxycholate, respectively; this is consistent with the presence of cysteinolic acid (mol wt 155) instead of taurine (mol wt 125). Enzymatic hydrolysis of the bile salts released cholic acid and chenodeoxycholic acid, respectively, and an amino acid that was identified as D-cysteinolic acid by direct comparison with an authentic sample. From these results, the bile salts in the bile of wild red seabream were identified as the conjugates of cholic acid and chenodeoxycholic acid with cysteinolic acid. 1H- and 13C-magnetic resonance spectra of the bile salts were also consistent with the proposed structure. The cysteinolic acid conjugates were found only in wild and not in cultured red seabream; this distinction seems to result from differences in dietary cysteinolic acid.

Animals↗

The measurement of bile acid-dependent and independent fractions of rat bile.

Bile flow and bile acid secretory rate in rate in rats with interruption of the enterohepatic circulation had a biphasic decay with the second slower slope less marked for bile flow. A direct relationship between both parameters was observed in these animals. by knowing the choleretic efficiency of bile acids calculated from the regression line, the total bile acid output and the volume of bile collected, the fraction of bile produced by other way than bile water carried by bile acids was estimated. This fraction was found to be about 65 percent of the total bile formed.

Animals↗

Effect of periodic long-term ethanol administration on biliary bile acids and bile secretion in the rat.

Hepatic bile flow and its bile acid composition were determined in a group of 23 rats receiving 20% (W/v) ethanol by daily intubations 5 times a week over a 10-12 week period and in a control group of 23 rats. The aim was to elucidate the well known role of alcohol in pancreatitis. Chronic ethanol administration resulted in a significant increase in 2-h bile production and bile secretion rates. Molar concentrations of total and individual bile acids were determined by the hydroxysteroid dehydrogenase method after thin layer separation. No significant differences in molar concentrations of total or separate bile acid were observed. Special attention was paid to free bile acids. A spot with a Rf value corresponding to cholic acid was found in 10 rats in each group. This was examined by mass spectrometry using direct inlet technique, but no free cholic acid could be identified. Thus it seems that the changes in the amounts of bile acids are not decisive for the origin of acute alcoholic pancreatitis but that increased bile flow caused by chronic alcohol ingestion may favour reflux of bile into the pancreas, resulting in pancreatitis.

Animals↗

The isolation and characterization of a bile ductule cell population from normal and bile-duct ligated rat livers.

The separation of bile ductule cells from Kupffer and sinusoidal endothelial cells in a suspension of non-parenchymal cells has been attempted. Bile duct ligation was performed so that a four-fold increase in the total number of non-parenchymal cells isolated from rat liver was attained and the proportions of both Kupffer and bile ductule cells were elevated. Rate zonal centrifugation, through a Ficoll gradient, partially separated the cells into two populations: (1) small cells (4-6 micrometer diameter) probably originating from the sinusoidal endothelium and (2) larger bile ductule and Kupffer cells (8-12 micrometer diameter). A more successful separation was achieved by isopycnic centrifugation through a linear metrizamide gradient. Bile duct ligation (14 days) altered the distribution of cells on the gradient and the peak containing bile ductule and Kupffer cells partially subdivided into the separate cell types. Antiserum raised against the bile ductule fraction was shown to be compatible with that raised against common bile duct tissue. gamma-glutamyl transpeptidase and leucine aminopeptidase activity were preferentially located in the rate zonal fraction containing bile ductule cells. Their specific activity increased after bile duct ligation as did that of beta-glucuronidase, which was raised in all cells.

Animals↗

Determination of individual conjugated bile acids in human bile.

A method has been developed and validated for the determination of the six major conjugated bile acids, cholesterol, and total phospholipids in bile of human subjects previously injected with 4-(14)C-cholesterol. The procedure is designed for use with 5-10 ml of duodenal or T-tube bile and eliminates difficulties associated with existing methods for bile acid determination, in particular the requirement for preliminary saponification under pressure or the use of paper chromatography. Saponification under pressure is employed only in steps where partial destruction of the steroid moiety of conjugated bile acids is not a crucial matter. A preliminary Folch extraction and washing step separated free cholesterol and phospholipids (bottom layer) from the six major conjugated bile acids (top layer). The conjugated bile acids were then fractionated cleanly by thin-layer chromatography to give four groups, the (14)C content of each of which was determined. A second aliquot of the top layer was used to determine (after deconjugation) the radioactivity ratio of deoxycholic acid to chenodeoxycholic acid for the two unresolved groups (dihydroxycholanoic acid conjugates with glycine and taurine, respectively). A third aliquot was used for determination of specific activities of the methyl esters of cholic, chenodeoxycholic, and deoxycholic acids derived from the total bile salts. Appropriate calculations yielded the concentration in bile of all six major bile acid conjugates.

Bile↗

Inhibition of bile salt excretion and bile flow by spasmolytic drugs. An additional therapeutic effect in the treatment of biliary colics?

The influence of the spasmolytic drugs hyoscin-N-butylbromide (HBB, Buscopan) and Extractum opii (E. opii) on bile flow, bile salt and bilirubin excretion is investigated in the cholecystectomized, unanaesthetized pig and compared with the results after acute, quantitative interruption of the enterohepatic circulation (EHC) by biliary drainage. The results demonstrate that HBB and E. opii induce a significant decrease in bile flow and bile salt excretion. A further analysis suggests that this effect is due to an inhibition of intestinal motility and transit time, followed by a delay of the EHC of bile salts with a decrease in biliary bile salt excretion and bile salt dependent bile flow. The results point out a second mechanism that might be responsible for the effectiveness of spasmolytic drugs in the treatment of biliary colics: the lowering of intraluminal pressure by inhibition of bile salt dependent bile flow.

Animals↗

Bile acid excretion during drainage of extrahepatic cholestasis with refeeding of bile.

Hepatic and renal excretion of individual bile acid conjugates were studied in four patients with extrahepatic cholestasis during 3 weeks of percutaneous transhepatic drainage with bile refeeding. The study involved isolation and determination by gas chromatography-mass spectrometry of individual bile acids separated into glycine, taurine and sulphate conjugates simultaneously in bile, serum and urine. In bile cholic, chenodeoxycholic and deoxycholic acids were chiefly found as glycine or taurine conjugates and in high concentrations, which indicated a large capacity of the post-cholestatic liver to excrete these conjugates. A minor portion of cholic, chenodeoxycholic and deoxycholic acids and all of lithocholic and 3 beta-hydroxy-5-cholenic acids in the bile were recovered as sulphate conjugates. The biliary concentration of sulphated bile acids was low, but increased during drainage with refeeding of bile indicating a gradually more efficient hepatic elimination of sulphated bile acids. The urinary concentrations of the individual bile acid conjugates decreased when the biliary concentration increased.

Aged↗

Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study.

Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid exchange between vesicles and micelles were monitored in a model bile system. Vesicles obtained from supersaturated model bile (cholesterol saturation index (CSI) 1.4; 10 g/dl) by KBr density gradient ultracentrifugation, were incubated with various bile salts: deoxycholate (DC), chenodeoxycholate (CDC), cholate (C), ursodeoxycholate (UDC), and their respective taurine and glycine conjugates. Vesicle integrity was assessed in a leakage-assay of carboxyfluorescein-loaded vesicles (0-15 min) and by the change in optical absorbance at 340 nm of a vesicle solution (0-50 min). Fluorescence increased within 1 min after addition of bile salt, and was stable within 5-10 min. After addition of bile salt, absorbance fell immediately and stabilized within 30 min. Fluorescence and absorbance were dependent on bile salt hydrophobicity and concentration. At several time points after addition of bile salt to vesicles (from 1 to 72 h), the extent of cholesterol nucleation was determined semiquantitatively and incubation mixtures were again subjected to ultracentrifugation to assess the lipid distribution among residual vesicles, de novo formed mixed micelles, and cholesterol crystals. Nucleation occurred within 0.5 h after exposure of vesicles to the hydrophobic bile salts DC or CDC, and the cholesterol/phospholipid (c/p) ratio of the vesicles showed a transient rise from 1.45 to 3-4 (at t = 0.5 h) that coincided with the appearance of mixed micelles. Then the vesicular c/p ratio decreased to 0.6-0.8 (at t = 24 h) concomitantly with increasing precipitation of cholesterol crystals. In the case of UDC, the most hydrophilic bile salt used, < 5% micellization, no nucleation, and a constant vesicular c/p ratio were observed. We conclude that under the conditions used in the present model study, the kinetics of cholesterol crystallization are governed by the hydrophobicity of the added bile salts and their capacity to form mixed micelles. The results emphasize the pivotal role of time, and the dynamic aspects of the processes involved in cholesterol crystal formation.

Bile↗

Phospholipid molecular species influence crystal habits and transition sequences of metastable intermediates during cholesterol crystallization from bile salt-rich model bile.

Despite its importance in cholesterol gallstone formation, crystallization of cholesterol from bile is poorly understood, especially with respect to the influences of other biliary lipids. We reported recently (Konikoff et al. J. Clin. Invest. 1992. 90: 1155-1160) that cholesterol can crystallize from model and native biles as filamentous crystals covered by a surface layer of lecithin molecules. During growth, filamentous crystals transformed via metastable intermediates into classical plate-like cholesterol monohydrate crystals. Using the same dilute (1.2 g/dl total lipid) bile salt-rich (97.5 moles %) model bile supersaturated with cholesterol, we have studied the effects of natural egg yolk, soy bean as well as single molecular species of lecithins, other phospholipids and related lipid classes on early filamentous cholesterol crystallization, as well as transformations between crystal habits and their growth to equilibrium cholesterol monohydrate plates. After extraction and derivatization, HPLC analysis revealed that the surfaces of filamentous crystals were enriched preferentially with lecithin molecular species having longer and more saturated sn-1 and sn-2 acyl chains compared to mixed lecithin species of whole bile. In contrast, the molecular species distribution of lecithins on equilibrium plate-like crystals resembled that of whole bile. After incubation of pre-formed anhydrous cholesterol and cholesterol monohydrate crystals in cholesterol-free lipid solutions, we demonstrated that surface-adsorbed lecithins were not preferentially enriched excluding nonspecific lecithin adsorption. Time-sequences and transformations between metastable crystalline intermediates were altered markedly by specific phospholipid species: model biles composed of saturated short-chain, medium-chain, and polyunsaturated long-chain lecithins induced rapid precipitation of short filamentous crystals that became plate-like slowly by an "arborization pattern." Long-chain saturated lecithins and natural sphingomyelins retarded cholesterol crystallization markedly, and filamentous as well as metastable intermediate crystals made transient appearances only after plate-like crystals had formed. These observations suggest that phospholipid molecular species and class influence the earliest events in cholesterol crystallization from bile salt-rich model bile. Furthermore, as the molecular species of lecithins adsorbed onto filamentous cholesterol crystals were more saturated than in whole bile and essentially identical to those in biliary vesicles, this finding provides chemical evidence for a vesicular origin of the critical cholesterol nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adsorption↗

Preoperative bile salt administration versus bile refeeding in obstructive jaundice.

BACKGROUND: Endotoxaemia due to intraluminal bile salt depletion may be a cause of renal failure in patients with obstructive jaundice. Administration of bile salts to these patients has been reported to decrease portal and systemic endotoxaemia during surgery and improve renal function. However, such changes have not been shown with bile refeeding. We compared the effect of preoperative bile salt administration with preoperative bile refeeding on renal function in patients with obstructive jaundice. METHODS: Sixteen patients with obstructive jaundice underwent percutaneous transhepatic biliary drainage--eight received oral bile salts (500 mg of sodium deoxycholate 8-hourly for 48 hours preoperatively) and the other 8 were refed the total bile output for the entire period of biliary drainage (median 13 days). Blood endotoxin levels and renal function were assessed before, during and after the operation. RESULTS: The number of patients with intraoperative portal and postoperative systemic endotoxaemia decreased after both forms of therapy. Renal function also improved in both the groups--all 4 patients with renal failure recovered. There was a significant increase in creatinine clearance postoperatively after bile salt therapy (from 65 ml/minute preoperatively to 87 ml/minute postoperatively). CONCLUSION: Refeeding of bile obtained by percutaneous catheter drainage is an effective, cost-free substitute for oral bile salts in patients with obstructive jaundice.

Adult↗

Regulation of classic and alternative bile acid synthesis in hypercholesterolemic rabbits: effects of cholesterol feeding and bile acid depletion.

The effect of cholesterol feeding (3 g/day) on bile acid synthesis was examined in 10 New Zealand white rabbits (NZW), 8 Watanabe heterozygous and 10 homozygous rabbits with partial and complete deficiencies of LDL receptors. After 10 days of cholesterol feeding, bile fistulas were constructed and bile acid pool sizes were measured. Cholesterol feeding increased plasma and hepatic cholesterol levels in all rabbit groups. Baseline bile acid pool sizes were smaller (P < 0.01) in heterozygotes (139 +/- 3 mg) and homozygotes (124 +/- 30 mg) than NZW rabbits (254 +/- 44 mg). After feeding cholesterol, bile acid pool sizes doubled with increased cholic acid synthesis in NZW and, to a lesser extent, in Watanabe heterozygous rabbits but not in homozygotes. Baseline cholesterol 7alpha-hydroxylase activity in NZW and heterozygotes declined 69% and 53% (P < 0.001), respectively, after cholesterol feeding. Sterol 27-hydroxylase activity reflecting alternative bile acid synthesis increased 66% (P < 0.01) in NZW and 37% in Watanabe heterozygotes but not in homozygotes after feeding cholesterol. Bile fistula drainage stimulated cholesterol 7alpha-hydroxylase activity but not sterol 27-hydroxylase activity in all three rabbit groups. These results demonstrated that dietary cholesterol increased hepatic sterol 27-hydroxylase activity and alternative bile acid synthesis to expand the bile acid pool and inhibited cholesterol 7alpha-hydroxylase in NZW and in Watanabe heterozygous rabbits but not in homozygotes with absent hepatic LDL receptor function. Thus, in rabbits, sterol 27-hydroxylase is up-regulated by the increased hepatic cholesterol that enters the liver via LDL receptors whereas cholesterol 7alpha-hydroxylase is controlled by the circulating hepatic bile acid flux.

Animals↗

A new rat bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro.

The rat treated with bile duct ligation (BDL) and furan is a unique animal model of massive bile ductular hyperplasia in which normal liver parenchyma is largely replaced with well-differentiated proliferated bile ductules. We have now developed a simple cell isolation procedure to obtain and culture viable bile ductular epithelial cells in high numbers and with a high degree of purity from the livers of BDL/furan-treated rats. Primary monolayer cell cultures were readily established when the isolated bile ductular epithelial cells were cultured in plastic tissue culture wells coated with rat tail tendon type I collagen plus bovine plasma fibronectin. Under these conditions, epidermal growth factor (EGF) was mitogenic for the cultured cells, and they retained phenotypic features typical of hyperplastic bile ductular epithelium but did not show evidence of ductal morphogenesis in vitro. In contrast, when the isolated bile ductular cells were cultured for 7 to 16 days in the presence of 25 ng EGF/mL and 10% fetal bovine serum on type I collagen gels, they formed into branching ductal structures whose ultrastructural features very closely resembled those of polarized hyperplastic bile ductules/ducts in vivo. Histological preparations of these gel cultures further showed that numerous ductal structures with defined lumens were present. Phenotypically, these ductal structures were completely surrounded by a thickened basement membrane that was strongly immunoreactive for laminin. Like their in vivo biliary cell counterparts, the epithelial cells comprising these ductal structures in culture also exhibited strong immunocytochemical staining reactions for cytokeratins 8 and 19, for glutathione S-transferase pi 7, and for luminal gamma-glutamyl transpeptidase, but they did not express immunoreactive albumin or alpha-fetoprotein. Occasional epithelial cells of the ductal structures, when examined in 10-day-old primary gel culture, showed strong nuclear staining for incorporated 5-bromo-2'deoxyuridine, indicating active cell proliferation. Our results support the development of a novel biliary epithelial cell culture model that has the potential of serving as a powerful tool for investigation of factors that regulate hyperplastic bile ductular morphogenesis, cell proliferation, and polarized cell functions in a structural form in vitro that mimics that of hyperplastic bile ductules induced in vivo.

Animals↗

Quantification of glycine and taurine conjugated bile acids in human bile using 1H NMR spectroscopy.

A simple method for quantification of conjugated bile acids in human bile using (1)H NMR spectroscopy is presented. Bile acids in human bile are essentially conjugated with either glycine or taurine. The amide NH resonances from the conjugated bile acids are invariably devoid of interfering signals in (1)H NMR spectra. Under physiologic conditions of human bile (pH approximately 7.0 to 7.7), amide signal intensities are attenuated due to the chemical exchange and hence quantitative estimation is precluded. In the present study, the quantity of total glycine and taurine conjugated bile acids could be obtained accurately by suppressing the amide exchange by reducing the pH slightly lower than physiologic value (6.0 +/- 0.5). Further, the quantity of glycine conjugated bile acids can be calculated accurately by subtracting the quantity of taurine conjugated bile acids from the total conjugated bile acids as determined from the present method.

Bile Acids and Salts↗

Adaptive regulation of hepatic bile salt transport. Effect of prolonged bile salt depletion in the rat.

Exposure of the liver to increased bile salt flux can increase the bile salt maximum secretory rate (SRm), presumably through the induction of new transport sites. The converse, i.e., the down-regulation of SRm upon bile salt deprivation, has not been demonstrated. We examined the effects of bile salt depletion for 24 h and 48 h on taurocholate SRm and bromsulphalein (BSP) SRm, and on [14C]taurocholate binding to isolated liver surface membranes in unrestrained external biliary fistula rats. Taurocholate SRm was significantly decreased by 35% and 51% in 24-h-depleted and 48-h-depleted rats, respectively, compared with control, sham-operated rats. Maximal taurocholate concentration in bile was also significantly lower in bile salt-deprived rats. In contrast, BSP SRm was not significantly different between depleted animals and controls. Bile salt depletion for 24 h and 48 h did not significantly alter liver surface membrane protein recovery and membrane enzyme specific activity, including Na+ + K+-ATPase. Specific [14C]taurocholate binding to liver surface membranes was significantly decreased by 25% in 24-h-depleted rats compared with control rats. In contrast to taurocholate SRm, bile salt depletion for 48 h did not result in further reduction of specific taurocholate binding sites. This study demonstrates that taurocholate SRm progressively decreased in 24-h- and 48-h-bile salt-depleted rats, this being consistent with adaptive down-regulation of hepatic bile salt transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

SK&F 97426-A: a novel bile acid sequestrant with higher affinities and slower dissociation rates for bile acids in vitro than cholestyramine.

SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within approximately 30 min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4 mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.

Animals↗

Effects of bile salt hydrophobicity on crystallization of cholesterol in model bile.

Precipitation of cholesterol crystals is an essential step in gallstone formation. In the present study we found much faster and more extensive precipitation of various cholesterol crystal shapes in whole model biles containing the hydrophobic bile salt taurodeoxycholate than in biles containing the relatively hydrophilic taurocholate. Addition of taurodeoxycholate to isolated cholesterol-phospholipid vesicles also induced more crystallization than taurocholate. Crystallization behaviour in whole model biles and in vesicles after addition of corresponding bile salts was very similar. The very hydrophilic bile salts tauroursodeoxycholate and taurohyodeoxycholate never induced crystallization from vesicles, and crystallization in corresponding whole model biles did not occur. These bile salts also reduced crystallization dose dependently after addition of taurodeoxycholate to vesicles. Ultracentrifugation experiments suggested a higher vesicular cholesterol-phospholipid bile salts. These findings indicate that bile salt hydrophobicity influences shape of cholesterol crystals and extent of crystallization, possibly by modulating the vesicular cholesterol-phospholipid ratio.

Bile Acids and Salts↗

Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract.

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis (H. bilis) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high-risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis-specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and / or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese (P < 0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and / or cholecystitis were 6.50 (95%CI 1.09 - 38.63) in the Japanese and 5.86 (1.31 - 26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.

Bile↗

Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane.

Unexplained bile acid malabsorption associated with diarrhoea that responds to cholestyramine was first described in 1973 but convincing evidence of the proposed mechanism--a defective active ileal bile acid transport--has never been substantiated. Active bile acid transport was quantified in vitro using brush border membrane vesicles prepared from terminal ileal biopsy specimens from 10 patients who fulfilled the criteria of idiopathic bile acid diarrhoea. They were recruited from 181 patients with bile acid malabsorption of various causes. Transport was quantified as in vitro Na+ dependent bile acid transport (INBAT), expressed as pmol taurocholate/mg brush border membrane protein/15 seconds, and in vitro Na+ dependent bile acid local transport capacity (INBALTC), expressed as pmol taurocholate/g ileal biopsy tissue/15 seconds. The lowest INBAT and INBALTC values in the 10 patients with idiopathic bile acid diarrhoea were well above the 10th centile values of a control group of 132 patients. Both INBAT (mean (range) 88 (30-136)) and INBALTC (158 (85-268)) values were significantly higher in the 10 patients than in the control group (INBAT: mean (range) 63 (1-244), INBALTC: mean (range) 98 (1-408)). Quantification of active ileal bile acid transport in these 10 patients with idiopathic bile acid malabsorption suggests that a genetic (carrier) defect is rare in adults.

Adult↗