Measurement Of Serum Bile Acids Research Articles

Serum bile acid measurements in women of European and South Asian ethnicity with or without gestational diabetes mellitus: A cohort study.

Investigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi-ethnic cohort of women who are lean or obese. Prospective cohort study. UK multicentre study. Fasting serum from participants of European or South Asian self-reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation. Bile acids were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Log-transformed data were analysed using linear regression in STATA/IC 15.0. Total bile acids (TBAs), C4, fasting glucose and insulin. The TBAs were 1.327-fold (1.105-1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162-fold (1.002-1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522-fold (1.193-1.942, P = 0.001). Obesity was associated with 1.420-fold (1.185-1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355-fold (1.140-1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.001) in women with GDM. Serum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity-specific ways. This suggests ethnicity-specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity-specific precision medicine for GDM are required.

Serum Bile Acid Measurements in Women of European and South Asian Descent with or without Gestational Diabetes Mellitus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of post-liver transplantation administration of ursodeoxycholic acid on serum liver tests and biliary complications: a randomized clinical trial

Endogenous hydrophobic bile acids may be a pathogenetic factor of biliary complications after orthotopic liver transplantation (OLT).This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA), when administered early after OLT, on serum liver tests and on the incidence of biliary complications. A total of 112 adult patients undergoing OLT were randomly assigned to one of two groups for receipt of UDCA (13 to 15 mg/kg/d for 4 weeks, n=56) or a placebo (n=56). All patients underwent serum liver testing and measurement of serum bile acids during the 4 weeks following OLT.Patients with T-tube underwent measurement of biliary bile acids during the 4 weeks following OLT.Biliary complications, as well as patient and graft survival rates, were analyzed during the follow-up period (mean of 65.6 months). At post-OLT days 7, 21 and 28, the UDCA-treated patients showed significantly lower levels of alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transpeptidase (all P less than 0.05).In addition, the UDCA-treated patients showed significantly lower incidence of biliary sludge and casts within the first year post-OLT (3.6% vs.14.3%; x2=3.953, P=0.047). However, there were no significant differences for the incidence of other biliary complications at post-OLT years 1, 3 and 5.The graft and patient survival rates were also similar between the two groups. UDCA, when administered early after OLT, improves results from serum liver tests and decreases the incidence of biliary sludge and casts within the first postoperative year.

Usefulness of combined measurement of serum bile acids and ferritin as additional prognostic markers to predict failure to reach sustained response to antiviral treatment in chronic hepatitis C

To investigate the relationship between serum levels of ferritin and bile acids (BA) and the response to antiviral treatment in chronic hepatitis C (HCV). A retrospective study was carried out on 35 control volunteers and 50 patients receiving interferon alpha-2b alone or plus ribavirin for 48 weeks. These were classified as sustained responders (SR) for >6 months after therapy (n = 17), non-responders (NR) (n = 27) and relapsers (RL) (n = 6). Before treatment, serum ferritin levels were determined by immunoturbidometry, 3alpha-hydroxyl-BA levels (S-3alpha-OH-BA) were assayed enzymatically and total (desulfated, deglucuronidated and deamidated) BA concentrations (STBA) by gas chromatography-mass spectrometry. STBA were lower in controls than in patients (SR < NR + RL). The highest levels of cholic acid and chenodeoxycholic acid families were found in NR + RL. Levels of cholic acid family were similar in controls and SR, whereas those of chenodeoxycholic acid family were higher in SR than in controls. A significant correlation between STBA (but not S-3alpha-OH-BA) and ferritin was found. Apparent value to predict the absence of a sustained response was calculated by combining elevated ferritin (>300 microg/mL) and STBA or individual BA species at different cut-off values. The best degree of certainty (100% specificity) was obtained using STBA >15 microM. These results recommend that larger prospective trials should be performed in chronic HCV patients to evaluate the usefulness of combined measuring of STBA and ferritin as additional prognostic markers to predict the existence of a very low probability of a sustained response to the current standard treatment, i.e. pegylated interferon in combination with ribavirin.

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.

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.

Serum bile acid concentrations in dairy cattle with hepatic lipidosis.

This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition.

Measurement of serum bile acids by gas chromatography-mass spectrometry (GC-MS)

Measurement of serum bile acids by gas chromatography-mass spectrometry (GC-MS)

A preliminary study on the effects of jejunocaecostomy in horses

SummaryIleal bypass by re‐section and jejunocaecostomy is a commonly performed surgery in horses, but has a reportedly lower success rate than other small intestinal surgeries. Lower success rates and chronic problems with diarrhoea, weight loss, protein, sugar and fat malabsorption, and Ca/P imbalance occur in man. The purpose of this study was to investigate changes in bodyweight, nutrient digestion and absorption, and serum and urine composition in horses before and 3, 12 and 27 weeks after ileal resection and side‐to‐side jejunocaecostomy. Four adult, healthy horses had a baseline CBC; serum creatinine, cholesterol, Na, K, Cl, Mg, Ca, P; digestion trial; xylose and fat absorption test; and serum total bile acid test. Digestion of dry matter, crude protein, total plant cell wall, cellulose, hemicellulose, and lignin; and urinary fractional excretions of Na, K, Cl, P and Ca were calculated. A one‐way analysis of variance compared baseline values to those obtained after caeliotomy and jejunocaecostomy (P&lt;0.05). Results include a significant decrease in serum calcium and total protein 27 weeks after surgery and a significant increase in FENa, FECa, and faecal metabolic organic matter 27 weeks after surgery. Bodyweight decreased significantly 3 weeks after surgery, but increased to greater than baseline values at 12 and 27 weeks after surgery. Vitamin A absorption curves were normal (sigmoid) before surgery and linear at all times after surgery. Serum cholesterol was significantly lower 27 weeks after surgery and a trend (P&lt;0.1) for a lower serum cholesterol was observed 3 weeks after surgery. No significant differences were apparent in serum electrolytes, faecal water, protein or fibre digestibility, xylose absorption or serum bile acid measurements. In summary, ileal bypass affected the horses minimally, but derangements of Ca metabolism, fat (fat soluble vitamin) absorption and microbial flora need further study.

Size exclusion chromatography for extraction of serum bile acids.

A major problem in the measurement of serum bile acids is their quantitative extraction from the high molecular protein matrix. In our hands, the standard techniques of adsorption and reversed-phase chromatography have yielded incomplete recovery for different bile acids (33-93%) and poor reproducibility. In contrast, with the novel extraction procedure of size exclusion chromatography, recovery was nearly quantitative (75-104%) and reproducibility was satisfactory. The described method allowed for a reliable determination of serum bile acids in healthy subjects and patients with liver cirrhosis. We conclude that size exclusion chromatography for serum bile acid extraction is more reliable than alternative techniques, because the separation by size is independent of solubility, charge, and polarity.

Serum unconjugated bile acids in patients with small bowel bacterial overgrowth

Concentrations of total and unconjugated bile acids in serum were measured fasting and 2 h postprandially in 9 patients with a positive [ 14C]glycocholate breath test consistent with small bowel bacterial overgrowth and in 13 controls. Gas-liquid chromatography-mass spectrometry (GLC-MS) and enzymatic-fluorometric assays were both used. In contrast to previous work, total serum bile acids were only occasionally elevated in patients with bacterial overgrowth. Total 2 h postprandial unconjugated bile acids, however, were elevated in 7 9 patients when measured by GLC-MS and in 6 9 when measured by the enzymatic-fluorometric method. The best separation between patients and controls was achieved by GLC-MS determinations of 2 h postprandial unconjugated cholic acid or primary bile acids, which were abnormal in 8 9 patients. This study indicates that measurement of serum bile acids may be a useful approach to the diagnosis of bacterial overgrowth, but would require accessible methods for separating and measuring cholic acid or unconjugated primary bile acids in post-prandial sera.

Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis

We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 μmol/L at 15 weeks' pregnancy to 0.6 μmol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p < 0.005), median concentrations of CG remained well within the normal range (0–1.5 μmol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p < 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p < 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude (a) that obstetric cholestasis is probably much more common than previously suspected and (b) that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus.

The diagnostic value of fasting individual serum bile acids in anicteric alcoholic liver disease: relation to liver morphology.

The aim of the present study was to evaluate the diagnostic value of measuring individual serum bile acids in patients with suspected alcoholic liver disease. A highly accurate and specific mass-fragmentographic technique with high sensitivity was used. Anicteric patients with fatty liver (n = 10) and liver cirrhosis (n = 9) were compared with healthy controls (n = 27). The measurement of serum bile acids did not discriminate patients with fatty liver from controls. In general, an increased serum level of cholic acid indicated more serious liver disease. Determination of chenodeoxycholic acid and deoxycholic acid did not add any further diagnostic information.

Bioluminescence measurement of primary bile acids using immobilized 7 alpha-hydroxysteroid dehydrogenase: application to serum bile acids

A simple, rapid, and sensitive bioluminescence method for measuring primary bile acids has been developed and validated. The method is based on enzymatic dehydrogenation of bile acids using a bacterial 7 alpha-hydroxysteroid dehydrogenase that is co-immobilized on Sepharose 4B beads with NADH:FMN oxidoreductase and a bacterial luciferase. The assay is specific for 7 alpha-hydroxy bile acids and has a detection limit of 0.5 pmol/tube, with a linear range of 0.5-50 pmol/tube. The assay shows good precision (6-8% intra-assay; 8-10% inter-assay). The values obtained with the bioluminescence assay showed good agreement with those obtained by gas-liquid chromatography, radioimmunoassay, or endpoint enzymatic assays. When applied to the measurement of serum bile acids, there was no interference from serum albumin, and the effect of other dehydrogenase activity in serum could be eliminated by heating the sample prior to assay. Since the method is rapid (1 minute), extremely sensitive (requires only 10 microliters of serum), and specific, it appears to be the best method currently available for the measurement of serum primary bile acids.

Influence of the gallbladder on serum bile acids.

Serum bile acids (SBA) were studied after a standard fatty meal in patients with gallbladder disease. Early postprandial bile acid values were found to be greater in patients with non-functioning gallbladders. Higher postprandial SBA values were found after cholecystectomy. Serum bile acid measurements were of no value in the assessment of gallbladder function.

The aminopyrine breath test and serum bile acids reflect histologic severity in chronic hepatitis.

To determine whether the aminopyrine breath test (ABT) and serum bile acid concentrations reflect histologic severity of chronic hepatitis, 56 patients were prospectively evaluated with liver biopsies and ABTs, and the results were compared to results of standard liver chemistry tests; 44 of these patients also had fasting and 2-hr postprandial serum bile acid measurements. Mean values for the ABT were significantly lower, and serum bile acids were significantly higher in patients with chronic active hepatitis with bridging or cirrhosis than in patients with mild chronic active hepatitis or chronic persistent hepatitis. Thirty of 35 patients with bridging or cirrhosis had ABTs less than 5.7% (mean of controls -2 S.D.) and 21 of 25 with mild chronic active hepatitis or chronic persistent hepatitis had values greater than 5.7% (sensitivity 0.86, specificity 0.84). Fasting and 2-hr postprandial bile acids were also more sensitive than standard chemistries in identifying patients with bridging or cirrhosis. Thus, the ABT and serum bile acids reflect histologic severity in chronic hepatitis patients and may be helpful in selecting patients for liver biopsy.

Letters to Editor

Serum bile acid measurements are not routinely performed in our laboratory and we are not aware of normative values for preterm infants. Thus we must make do with more arcane liver function tests to monitor hepatic normality. The absence of neurologic toxicity in our small patients was documented on serial observation's of their performance on the Brazelton scale (modified for prematures).

Hepatitis B antigen and antibody and tests of liver function: a prospective study of 310 hospital laboratory workers.

This prospective epidemiological study of a population of hospital laboratory workers, exposed to hepatitis routinely, studied the prevalence of the presence of hepatitis B antigen and antibody (HBsAg and HBsAb, respectively) over a 26-month period among these workers. Tests of liver functions, including measurement of serum bile acids, were also performed. 111 were studied once and 199 employees were measured at least 2 times. Though the prevalence of antigen for hepatitis was 1.7% and that for antibody was 23.9%, the rate of hepatitis attack was only 3% per year, a percentage consistent with the expected sporadic occurrence of hepatitis viral infection in such a population. Attempts were made to isolate risk factors. The following were determined: 1) exposure to body fluids, 2) exposure to body tissue, and 3) increasing duration of employment. Sex was not found to be a significant difference. When information on prior transfusion or attack of hepatitis was elicited from the study population, those with 1 or the other showed a much higher prevalence of Hb marker; this prevalence of marker increased if both transfusion and hepatitis viral attack had occurred in the past. However, the clinical significance of a positive HB marker with or without other risk factors (including alcohol ingestion and use of oral contraceptives) was negligible. It was found that the prevalence figures of hepatitis antibody underestimate the incidence of hepatitis infection. Liver function tests were routinely normal in all cases (i.e., with or without previous hepatitis infection or presence of antibody or marker) except where acute hepatitis infection was present. The spread of hepatitis among laboratory personnel is not considered a great public health hazard.

Specificity and Cross Reactivity in Bile Acid Radioimmunoassays Serum Bile Acids, Radioimmunoassay

Abstract In man there are four main bile acid fractions and within each fraction there is the possibility of at least three bile acid moities - two conjugated and one unconjugated. Bile acids thus present a considerable challenge to radioimmunoassay techniques. Few of the antisera described to date are satisfactory in that they do not show equal reactivity to each of the moities to be assayed, and many have unacceptable cross reactivity properties. Clearly there is need for caution and development in this field. The first application of radioimmunoassay (RIA) techniques to the measurement of serum bile acids was made by Simmonds, Korman, Go and Hofmann in 19731. Because of its unique sensitivity and ease of application, RIA has been used not only to determine the increased serum bile acid levels found in liver disease, but also to monitor the clearance of bile acids from the peripheral circulation of normal subjects, to provide 24 hour serum bile acid profiles in normal subjects and even to assay the low ...

Clinical significance of serum bile acid measurement in liver diseases.

To determine the clinical significance of serum bile acid measurements, changes in the serum bile acid composition in liver diseases and endogenous bile acid clearance due to test meal loads were investigated. In the case of changes in the serum bile acid composition, a characteristic pattern of a remarkable increase of chenodeoxycholic acid (CDCA) was found in fulminant hepatitis. In patients with acute hepatitis, increases in CDCA were somewhat greater than those of cholic acid (CA) and there was tendency for these changes to precede changes in other liver function tests. In cases of extrahepatic obstructive jaundice, the CA/CDCA ratio was a large value exceeding 1.0. In investigations of endogenous bile acid clearance, serum bile acid concentration two hours after the text meal load clearly reflected the hepatic disorder and it was useful in differentiating between active and inactive form in chronic hepatitis and compensation and decompensation in liver cirrhosis.