Measurement Of Bile Acids Research Articles

Preeclampsia with Abnormal Liver Function Tests Is Associated with Cholestasis in a Subgroup of Cases

Objective: To investigate whether women with preeclampsia and abnormal liver function tests have raised serum bile acids. Design: Measurement of serum bile acids in serum specimens collected at the John Radcliffe Hospital, Oxford. Setting: Imperial College School of Medicine. Sample: Stored sera from 37 women with preeclampsia and abnormal liver function tests and from 19 controls. Methods: Enzymic total bile acid assay. Main outcome measures: Total bile acid levels. Results: Women with preeclampsia and abnormal liver function tests had higher median bile acid levels than controls (5.7 vs. 3.2, p = 0.01). The reason for the raised median serum bile acid levels in the patient group is that three (8%) women with preeclampsia had markedly raised serum bile acids levels. There were no obvious clinical or biochemical features specific to these patients. Conclusions: The pathological mechanisms causing hepatic impairment in some women with preeclampsia may predispose to cholestasis. As some women with preeclampsia and abnormal liver function complain of pruritus, we recommend checking the serum bile acids in this group of women. If these acids are raised the fetal prognosis may be adversely affected.

Bifidobacterium animalis strain DN-173 010 hydrolyses bile salts in the gastrointestinal tract of pigs

Background: Bile salt hydrolase (BSH) activity is widespread among ingested bifidobacteria and lactobacilli. It is sometimes considered to be beneficial because of its putative lowering effect on cholesterol absorption and sometimes considered to be deleterious because it may compromise normal fat absorption and even promote the formation of secondary cytotoxic bile acids by the resident intestinal flora. However, the true hydrolysis of bile salts in vivo by ingested living bacteria remains unexplored. The aim of the study was to examine whether or not Bifidobacterium animalis DN-173 010 (used in fermented milks), which demonstrates a BSH activity in vitro, was also active in vivo during its transit in the intestine of pigs. Methods: Direct measurement of total and unconjugated bile acids reabsorbed into the portal vein was done, before and after the pigs had been treated for 2 weeks with two daily doses of­≈ 3.5·10[Formula: See Text] colony-forming units of living (6 pigs) or inactivated B. animalis (6 pigs). Results: None of the treatments modified the portal serum concentration of total bile acids over a 6-h postprandial period. Unconjugated bile acids represented up to 44% and 53% of total bile acids after 1 and 2 weeks of treatment with living bacteria, respectively, compared with only 25% (P < 0.05) before treatment or after 1 or 2 weeks of treatment with inactivated bacteria. Conclusions: Living B. animalis DN-173 010 exhibited a BSH activity in the gastrointestinal tract of pigs, most probably in the small bowel. There was no sign of increased formation of secondary bile acids beyond the hydrolysis reaction.

Accurate enzymatic measurement of fecal bile acids in patients with malabsorption

Quantitation of fecal bile acid excretion can help elucidate the cause of diarrhea or steatorrhea. Fecal bile acids can be measured with gas chromatography–mass spectrometry, but this is time-consuming, expensive, and not available for clinical use. Relatively simple enzymatic methods have been described for the measurement of fecal 3α-hydroxy bile acids, but these have not been validated in patients with gastrointestinal disease. We found that an enzymatic method yielded falsely low results in patients with malabsorption syndromes for two reasons: First, the preliminary hydrolysis step did not completely deconjugate bile acids, precluding their extraction into diethyl ether for enzymatic assay. Second, long-chain fatty acids inhibited 3α-hydroxysteroid dehydrogenase activity. By increasing the duration of hydrolysis and the concentration of enzyme, we developed a simple, accurate, and reproducible method for measuring fecal 3α-hydroxy bile acids that agreed well with values obtained with the use of gas chromatography–mass spectrometry ( R = .95), both in normal subjects and in patients with malabsorption syndromes.

Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus

Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus—related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting. (Liver Transpl 2003;9:437-443.))

Uninary sulfated bile acids: A new simple urine test for cholestasis in infants and children

Background/Purpose: Measurement of urinary sulfated bile acid (USBA) has been reported as a simple urine test that reflects the degree of cholestasis. The authors report the diagnostic value of this new laboratory test in various cholestatic conditions affecting infants and children. Methods: A urine sample was collected from 4 surgical neonates with parenteral nutrition–induced cholestasis and 48 patients with biliary atresia (BA). USBA was measured by direct enzymatic assay. Results: In 3 patients receiving parenteral nutrition, USBA increased with caloric gains. For one surgical patient, a decrease in calories because of liver dysfunction resulted in a decrease of USBA, closely reflecting the fluctuations of caloric intake. In patients with BA, a significant positive correlation was noted between serum bile acid and USBA (r = 0.85; P <.01). Ten of 14 febrile episodes in 6 patients with liver dysfunction and increased C-reactive protein showed elevated USBA, thus diagnosed as cholangitis. Four febrile episodes caused by viral infection showed no elevation of USBA. Conclusions: USBA is a simple and sensitive noninvasive test reflecting the degree of cholestasis in infants and children. USBA correlated highly with serum bile acid levels and may be helpful in diagnosis of cholestasis caused by cholangitis without blood sampling. J Pediatr Surg 37:1707-1708. Copyright 2002, Elsevier Science (USA). All rights reserved.

A prospective study of serum bile acid concentrations and colorectal cancer risk in post-menopausal women on the island of Guernsey.

Secondary bile acids produced by the action of the colonic microflora may increase risk of colorectal cancer. Serum bile acid concentrations reflect the faecal bile acid profile and may be of value as biomarkers of risk of colorectal cancer. In a pilot investigation we examined: (i) the reproducibility of measurements of serum bile acids in two blood samples collected several years apart; and (ii) the hypothesis that relatively high levels of secondary bile acids, particularly deoxycholic acid, would be positively associated with an increased risk of colorectal cancer in a prospective study of 3680 women in Guernsey. There was poor reproducibility between repeat measurements of absolute serum concentrations of bile acids, but there was moderately good reproducibility for the ratios of serum concentrations of deoxycholic/cholic acid, lithocholic/chenodeoxycholic and secondary/primary bile acid concentrations (duplicate blood samples were available for 30 women). There were no significant differences in ratios of serum secondary to primary bile acids or in absolute concentrations of bile acids between the 46 women who developed colorectal cancer and their matched controls, although there was a suggestion that an increased risk was associated with a high ratio of deoxycholic/cholic acid (relative risk in top third compared to lower third=3.92 (95% CI 0.91-17.0, P for trend=0.096). These findings suggest that the ratios of serum bile acid concentrations are sufficiently reproducible for epidemiological studies, but that a larger study than our own is needed to adequately test the hypothesis of their relation to cancer risk.British Journal of Cancer (2002) 86, 1741–1744. doi:10.1038/sj.bjc.6600340 www.bjcancer.com© 2002 Cancer Research UK

Role of bile acid measurement in pregnancy

The diagnosis of obstetric cholestasis (OC) has serious implications for maternal, and especially fetal, health. Total serum bile acid concentration is an important investigation in any woman with itching in the absence of a rash during pregnancy. Results should be available within 1-2 working days. Pruritus plus raised total bile acids in the third trimester suggests a diagnosis of OC. Other biochemical abnormalities, usually a raised alanine aminotransferase, accompany or follow the finding of raised bile acids. Bile acids are sensitive, but not specific, markers for OC. The diagnosis is one of exclusion. The clinician should remain alert to other causes of liver dysfunction, either specific to pregnancy or not. Effective treatment is available that improves maternal biochemical indices and well-being. It is not clear whether such treatment reduces the risks to the fetus. More active management of OC pregnancies has reduced the associated fetal and perinatal mortality.

Effect of Chronic Administration of Tauro-hyodeoxycholic Acid on Biliary Bile Acid Composition and on Biliary Lipid Secretion in Humans

Tauro-hyodeoxycholic acid is a hydrophilic bile acid of potential interest for treating cholestatic liver diseases. Bile acid pool is enriched with this bile acid during acute administration in patients with interrupted enterohepatic circulation. The aim of our study was to check the effect of chronic administration of tauro-hyodeoxycholic acid on biliary lipid composition and secretion in man with intact enterohepatic circulation. We studied 7 dyspeptic patients before and during taurohyodeoxycholic acid 750 mg/day given for 6-8 weeks. We measured bile acid composition in duodenal aspirate, and biliary lipid secretion was also measured in 5 of these patients using a duodenal perfusion technique. Tauro-hyodeoxycholic was undetectable in duodenal aspirate in all patients before treatment, and was 2%, 4%, 5%, 7%, 7%, 8% and 13% of biliary bile acid during treatment in individual patients. The proportion of cholic, deoxycholic, chenodeoxycholic ursodeoxycholic and lithocholic acid was similar before and during treatment. Bile acid duodenal output remained unchanged during taurohyodeoxycholic by comparison with pretreatment with median difference -0.3 mmol (95% confidence interval 1.6 mmol). The corresponding difference for duodenal cholesterol and phospholipid output was 0.1 mmol (0.2 mmol) and 0.2 mmol (0.6 mmol). By contrast with acute administration in patients with interrupted enterohepatic circulation, chronic administration of tauro-hyodeoxycholic to man with intact enterohepatic circulation has little effect on biliary lipid composition and secretion.

Effect of Chronic Administration of Tauro-hyodeoxycholic Acid on Biliary Bile Acid Composition and on Biliary Lipid Secretion in Humans

Background: Tauro-hyodeoxycholic acid is a hydrophilic bile acid of potential interest for treating cholestatic liver diseases. Bile acid pool is enriched with this bile acid during acute administration in patients with interrupted enterohepatic circulation. The aim of our study was to check the effect of chronic administration of tauro-hyodeoxycholic acid on biliary lipid composition and secretion in man with intact enterohepatic circulation. Methods: We studied 7 dyspeptic patients before and during taurohyodeoxycholic acid 750 mg/day given for 6-8 weeks. We measured bile acid composition in duodenal aspirate, and biliary lipid secretion was also measured in 5 of these patients using a duodenal perfusion technique. Result: Tauro-hyodeoxycholic was undetectable in duodenal aspirate in all patients before treatment, and was 2%, 4%, 5%, 7%, 7%, 8% and 13% of biliary bile acid during treatment in individual patients. The proportion of cholic, deoxycholic, chenodeoxycholic ursodeoxycholic and lithocholic acid was similar before and during treatment. Bile acid duodenal output remained unchanged during taurohyodeoxycholic by comparison with pretreatment with median difference-0.3 mmol (95% confidence interval 1.6 mmol). The corresponding difference for duodenal cholesterol and phospholipid output was 0.1 mmol (0.2 mmol) and 0.2 mmol (0.6 mmol). Conclusions: By contrast with acute administration in patients with interrupted enterohepatic circulation, chronic administration of tauro-hyodeoxycholic to man with intact enterohepatic circulation has little effect on biliary lipid composition and secretion.

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen

Background. The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. Aims. To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. Methods. Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. Results. Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. Conclusions. Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Proton magnetic resonance assay of total and taurine-conjugated bile acids in bile

Biliary bile acids, coexisting with phospholipid and cholesterol, are partly conjugated with taurine. In the present report we show that total and taurine-conjugated bile acids in bile can be simultaneously and quantitatively measured by high-resolution (1)H-nuclear magnetic resonance ((1)H-NMR) spectroscopy. We used a 7.05-Tesla NMR spectrometer to obtain the (1)H-NMR spectra of model and biological biles. Only addition of trimethylsilyl-3-propionic acid sodium salt-D(4) (TSP) to each sample as an internal standard was required in preparation for (1)H-NMR measurement. In (1)H-NMR spectra of rat bile, peaks of C-18 methyl protons of bile acids and of C-25 methylene protons on the taurine moiety of taurine-conjugated bile acids were detected at 0.7 ppm and 3.1 ppm, respectively. Peak areas, of C-18 and C-25 peaks, increased in proportion to the concentrations of bile acids or taurine-conjugated bile acids, even in the presence of phospholipid and cholesterol. The accuracy of NMR measurement of total and taurine-conjugated bile acids was confirmed by comparing the results of NMR with those of enzyme-fluorimetry. The results clearly demonstrate that (1)H-NMR spectroscopy can be applied to the quantitative determination of total and taurine-conjugated bile acids in bile without troublesome preparative steps.

Outcomes after extrahepatic portosystemic shunt ligation in 49 dogs.

To evaluate outcomes after attenuation of extrahepatic portosystemic shunts in dogs using surgical silk. Retrospective study. Case records were reviewed for degree of surgical attenuation, experience of the primary surgeon, perioperative mortality and problems related to persistent portosystemic shunting or shunt ligation. Presence of portosystemic shunting after surgery was evaluated by ammonia tolerance testing, measurement of postprandial serum bile acid, plasma urea and cholesterol concentrations and liver enzyme activity. The influence of age, postocclusion portal pressure, primary surgeon, degree of attenuation and postoperative biochemical findings on the occurrence of postoperative problems was assessed. The mortality rate was 2.1%. Shunt attenuation was complete in 34% and partial in 66% of dogs. Portal hypertension necessitating ligature removal was encountered in only one dog. Five dogs experienced neurological abnormalities (seizures or ataxia), possibly as a manifestation of 'postligation seizure syndrome'. Postoperative liver function was normal in 78% of dogs, including 70% with partial shunt attenuation. Experience of the surgeon was related positively to outcome after partial attenuation (P = 0.002). Postoperative biochemical evidence of abnormal liver function was the most sensitive predictor of recurrence of clinical signs referable to persistent portosystemic shunting. In the hands of an experienced surgeon, surgical attenuation of single extrahepatic shunts was safe and effective, even in animals with partial attenuation. Most dogs with biochemical evidence of persistent shunting suffer relapse of clinical signs within 18 months of surgery. Postligation neurological syndromes of variable intensity may be more common than previously thought.

Ratio of primary and secondary bile acids in feces: possible marker for colorectal cancer?

Increases in fecal bile acids may play a role in colorectal carcinogenesis. The authors tested the hypothesis that high concentrations of primary and secondary bile acids are more common in patients with colon cancer than in patients with other gastrointestinal diseases. In this retrospective study the secondary bile acid deoxycholic acid and the primary bile acid cholic acid were measured in the feces by enzyme-linked immunoabsorbent assay in 63 patients with colorectal cancer, 24 patients with gastric cancer, 11 patients with biliary disorders, and 47 healthy volunteers. Preoperatively, the mean deoxycholic acid values tended to be higher and the cholic acid values were significantly lower in patients with colorectal cancer than in healthy subjects. Patients with other gastrointestinal diseases had lower deoxycholic acid and cholic acid values than healthy subjects. In healthy subjects the deoxycholic acid to cholic acid ratio ranged from 0.10 to 2.86 (mean, 0.88), but in almost two-thirds, the ratio did not exceed 1. In contrast, the mean preoperative ratio in patients with colorectal cancer was 2.26 (range, 0.06-7.17; P < 0.0001) and tended to be higher in patients with advanced cancer and in those with sigmoid and rectal tumors. If 1.1 is taken as the upper limit of normal for deoxycholic acid to cholic acid ratio, 67 percent of patients with colorectal cancer had an abnormal value preoperatively. A high deoxycholic acid concentration and deoxycholic acid to cholic acid ratio may be indicators of colorectal cancer. Further study is needed to improve sensitivity and specificity, perhaps by combining fecal bile acid measurements with other tests, and a large prospective trial may be warranted to determine whether these measurements have value in screening for this common cancer.

Effect of octreotide (Sandostatin 201-995) on bile flow and bile components.

Octreotide (Sandostatin 201-995) has an inhibitory effect on gastric, intestinal, and pancreatic secretions and hepatic and splachnic blood flow. We examined the effects of octreotide on bile flow and bile components in 10 patients with T-tube choledochostomy. A Fogarty balloon catheter was inserted distal to the T-tube of these patients for measurement of bile flow and bile components. Bile samples were obtained to analyze bile acid, phospholipid, lipoprotein, and cholesterol, and bile flow measurements were performed every 15 min for a period of 90 min before study and after normal saline and octreotide administrations. While octreotide had an inhibitory effect on bile flow, the concentrations of bile acid, phospholipid, and lipoprotein in bile were increased with octreotide.

Simultaneous determination of bile acids in rat liver tissue by high-performance liquid chromatography

A method for the simultaneous determination of bile acids in rat liver tissue by high-performance liquid chromatography was developed. Without prior fractionation and alkaline hydrolysis, 30 unconjugated, glycine- and taurine-conjugated bile acids were detected by post-column enzymatic reaction and fluorescence detection. They were separated on a reversed-phase column using a linear gradient solvent system of 10 m M tribasic ammonium phosphate–acetonitrile–methanol (44:12:5, v/v/v) and 20 m M dibasic ammonium phosphate–acetonitrile–methanol (2:1:2, v/v/v). The limits of detection were 1–5 pmol, and calibration curves were linear for concentrations ranging between 10 and 4000 pmol per 10 μl injection. This rapid and reliable method is effective for measuring bile acid levels in liver tissue not only of rats but also of patients with hepatobiliary and other diseases.

Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis

Objective: Ursodeoxycholic acid (UDCA) improves liver biochemistries and enriches the bile with UDCA in patients with primary biliary cirrhosis. The aim of this study was to determine whether the degree of enrichment of bile correlated with that of serum and whether either of these measures correlated with improvement in measures of liver disease. Methods: In a randomized study, biliary and serum bile acid analyses were performed at entry and after 2 yr of UDCA or placebo. Results: The percentage of ursodeoxycholic acid in bile increased by 42% in the UDCA group (n = 61) compared with 8% in the placebo group (n = 57) ( p < 0.0001). Measurement of serum bile acids in 32 patients (18 ursodeoxycholic acid, 14 placebo) indicated that at 2 yr, ursodeoxycholic acid comprised 65% of serum bile acids in the treated group and 7% in the placebo group. Agreement between bile and serum was fair (r = 0.75, p ≤ 0.00002) because in some patients, plasma but not biliary bile acids were enriched with UDCA. Changes in biliary ursodeoxycholic acid correlated significantly but weakly with the changes in serum alkaline phosphatase, AST, bilirubin, and in Mayo risk score. Correlations between changes in serum bile acid composition and biochemical measures of disease activity were even weaker. Conclusion: The measurement of biliary bile acids is superior to that of serum bile acids for assessing the compliance and changes in the circulating bile acids in patients receiving ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Furthermore, measures to further increase the proportion of ursodeoxycholic acid in circulating bile acids should be explored.

Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38-57%), right 45% (2-62%) vs. control subjects 59% (38-70%), P < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1-25%)] was lower than in the patients with right hemicolectomy [19% (0-69%)] and control subjects [24% (7-50%)] P < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 mumol g-1) than in those with left hemicolectomy (0.048 mol g-1), which coincided with a higher cytolytic [right 49% (3-93%), left 2% (1-37%)] and alkaline phosphatase activity [right 6.7 U mL-1 (1.2-40.1 U mL-1), left (2.0 U mL-1 (1-25.7 U mL-1), both P < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.

Plasma Lathosterol as a Screening Test for Bile Acid Malabsorption Due to Ileal Resection: Correlation with 75SeHCAT Test and Faecal Bile Acid Excretion

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Serum 7α-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea

To assess the reliability of serum 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-3ox-C) in the differential diagnosis of bile acid induced diarrhoea by comparison with 75selenohomocholyltaurine whole body retention (SeHCAT WBR). One hundred and sixty-four patients with chronic diarrhoea were investigated prospectively in two centres (Edinburgh and Sweden) by two different tests which measure bile acid loss or synthesis: the SeHCAT test which measures the 7-day SeHCAT WBR and serum 7 alpha-3ox-C which reflects the rate of bile acid synthesis. Forty-six patients had SeHCAT WBR of less than 10% (19 with ileal disease or resection, nine with idiopathic bile acid induced diarrhoea and 18 with miscellaneous causes for bile acid induced diarrhoea). All patients with ileal or idiopathic disease showed a favorable response to treatment as did 13 of the miscellaneous group. Serum 7 alpha-3ox-C was raised in all subjects with ileal disease/resection, seven patients with idiopathic disease and all subjects in the miscellaneous group who responded to treatment. Sixteen out of 118 patients with SeHCAT WBR greater than or equal to 10% had raised serum 7 alpha-3ox-C. The positive predictive value of serum 7 alpha-3ox-C was 74%. The high negative predictive value (98%) of serum 7 alpha-3ox-C indicates the possible use of this test for excluding bile acid malabsorption in this population. All but two subjects who responded to treatment had raised serum 7 alpha-3ox-C concentrations. The possibility that the sensitivity of the test can be improved by repeat testing needs to be further investigated. There was a significant correlation between fractional catabolic rate (FCR) SeHCAT and serum 7 alpha-3ox-C (r = 0.63, P < 0.0001). Further data are required to validate the reference range in women over 70 years of age.

Randomized, Double-Blinded, Placebo-Controlled Study of Effect of Wheat Bran Fiber and Calcium on Fecal Bile Acids in Patients With Resected Adenomatous Colon Polyps

Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.