Search

Paired serum bile acid (SBA) samples from 30 dogs with presumptive hepatobiliary disease and 30 apparently healthy dogs were submitted to three diagnostic laboratories to validate agreement between these facilities. Sensitivities and specificities ranged from 50% to 70% and from 74% to 85%, respectively, for all laboratories. The κ index confirmed almost perfect agreement between laboratories. Variation in sample handling and processing by different laboratories should not be considered a primary factor when aberrant SBA values are encountered. Documenting agreement between laboratories is essential as inconsistencies could direct unnecessary medical or surgical intervention when patients are evaluated at different hospitals during the course of their disease.

Serum bile acid concentrations were measured after food had been withheld for 12 hours (fasting serum bile acid [FSBA] concentration) and 2 hours after a meal (post-prandial serum bile acid [PSBA] concentration) using a direct enzymatic procedure in 108 cats clinically suspected of having hepatobiliary disease. In all cats, liver tissue was examined histologically to confirm the diagnosis. Twenty-six cats did not have histologic evidence of hepatobiliary disease and served as controls. The remaining 82 cats had hepatobiliary disease including hepatic lipidosis (n = 20), portosystemic vascular anomaly (n = 24), hepatic necrosis (n =13), hepatic neoplasia (n = 8), or cholestatic hepatic disease(n = 17). Sensitivity and specificity of measuring FSBA and PSBA concentrations were calculated for each test alone and when results were interpreted in combination (ie, in series and in parallel), and were compared with sensitivity and specificity of routinely used serum biochemical tests, including measuring serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase, and measuring serum concentrations of cholesterol, BUN, and total bilirubin. When tests were considered individually, determination of FSBA and PSBA concentrations had higher specificity than did the other tests (using a cutoff of 15 mumol/L for FSBA concentration and of 20 mumol/L for PSBA concentration). Determination of PSBA concentration had the highest sensitivity of all single tests in cats with hepatic lipidosis, portosystemic vascular anomaly, or cholestasis; determination of alanine aminotransferase activity or PSBA concentration had the highest sensitivity for cats with hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

A rapid and simple on-line purification procedure was developed for determining the conjugated bile acids in human fluids by high-performance liquid chromatography (HPLC). Biological samples were diluted and directly injected without further treatment onto a pre-column dry-packed with 40-microns octadecylsilica and installed at the injector loop position. After washing the pre-column with 40% methanol in acetate buffer and then with water, the retained compounds were back-flushed by the mobile phase onto the analytical column during the normal course of chromatography. The method was found to be accurate and reproducible. The levels of conjugated bile acids in serum, duodenal bile and gastric juice from patients with hepatobiliary and gastric diseases were determined by on-line pre-column clean-up and reversed-phase HPLC.

A reversed phase high performance liquid chromatographic method for the high sensitivity determination of individual bile acids in serum using a C18 column with a ternary solvent system combined with fluorometric techniques using immobilized enzymes is described. A computer-assisted diagnosis system using pattern recognition was developed to assist the clinical diagnosis of various liver and biliary diseases. A total consistency rate of 95% can be reached using this system.

The fasting and 2 h postprandial total serum bile acid concentrations (FSBA and PSBA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin (Total), and retention of bromosulphthalein were determined in a group of dogs with various hepatobiliary disorders as well as in a group of dogs with other diseases than hepatobiliary disorders. Although FSBA and PSBA were generally elevated in cases of hepatobiliary disorders, no distinction between different disease groups could be made based solely on FSBA and PSBA. FSBA and PSBA were found to be relatively sensitive and specific parameters compared to the other hepatic tests. PSBA tended to be superior to the other parameters investigated in terms of sensitivity, specificity, positive predictive value, and negative predictive value.

Fasting and postprandial concentrations in serum of 3 alpha-hydroxy-bile acids and gamma-glutamyl transferase were measured in 138 consecutive patients, 62 with (D) and 76 without (D) hepatobiliary disease. The maximum efficiencies of the three tests--that is, the fractions of patients allocated correctly to the D or D group at the optimum discrimination values--were 0.85, 0.84, and 0.83, respectively. Furthermore, the predictive values and nosographic sensitivities and specificities were rather similar. When the three tests were combined, the nosographic sensitivity increased significantly to a value of 0.84, and the corresponding specificity was 0.91. The diagnostic value of the absolute postprandial increase in serum bile acid concentration was slightly inferior to the diagnostic values of the fasting and postprandial serum bile acid concentrations and, finally, the relative postprandial serum bile acid increase was of no diagnostic value at all.

Fasting concentrations of S-cholate, S-chenodeoxycholate, S-aminotransferases, S-bilirubin, S-alkaline phosphatases, and S-glutamyltransferase were determined in 564 outpatients with disorders of the liver and gastrointestinal tract. Unsulphated conjugates of cholic (fS-C) and chenodeoxycholic acid (fS-CDC) were determined by radioimmunoassay. In patients with increased serum bile acid concentrations fS-C and fS-CDC were linearly correlated, and the fS-C/fS-CDC ratio was similar in all patient groups. The incidence of false-positive results of fS-CDC was probably due to inadequate fasting and comparison of fS-C only with the liver tests. In 51 patients with verified cirrhosis fS-C was significantly correlated with S-bilirubin in a semilogarithmic relation but not with S-alkaline phosphatases or S-glutamyltransferase. fS-C was found to be a sensitive indicator of liver disease in the anicteric stage. Of 207 patients with inflammatory bowel disease, 63 had 1 or several of the results of liver tests for cholestasis elevated. There was no correlation between the different tests. In these patients and all patients with gastrointestinal disorders the commonest single finding was an elevation of S-alkaline phosphatases not associated with cholestasis.

Individual non-sulfated bile acids in the serum of 65 patients with hepatobiliary diseases were quantitated by mass fragmentography. Serum with deuterium labeled deoxycholic acid as an internal standard was hydrolyzed with strong alkali, extracted with ether after acidification under cooling, and quantitated by mass fragmentography as the hexafluoroisopropyl-trifluoracetyl derivatives. In obstructive jaundice, the ratio of cholic to chenodeoxycholic acid was significantly higher than others. Cholic or chenodeoxycholic acid levels were correlated with total bilirubin levels in obstructive jaundice and acute hepatitis. Lithocholic acid value was independent of the degree of liver injury. Total bile acid value was helpful in estimating the extent of liver cell injury and cholestasis, and these two pathological conditions can be distinguished to some extent by cholic to chenodeoxychoic acid ratio.

We review the estimation of total and individual serum bile acids to detect the presence and nature of hepatobiliary disease. The different methods for measuring serum bile acids are discussed.

A crude 7alpha-hydroxysteroid dehydrogenase isolate from P. testosteroni requires NADP specifically and provides a simple and specific means for the determination of 7alpha-hydroxy bile acids and their conjugates. A specific and reliable enzymatic-fluorimetric method for the quantitative measurement of the primary bile acids in serum is described. Overall recovery from normal and jaundiced serum averaged 85%. The mean concentration of serum 7alpha-hydroxy bile acids in fasting, healthy subjects was 2.5 mumoles/1 (S.D. 1.45 AND RANGE 1.2-6.3), averaging 73% (S.D. 11.5) of the total, measured as the 3alpha-hydroxy bile acid concentration. In parenchymatous liver disease and cholestatic hepatobiliary disorders, the proportion of 7alpha-hydroxy bile acids was significantly increased, mean 92.5% (S.D. 6.6)(p less than 0.001).

Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use.

The value of serum bile acids (SBA) in the diagnosis of hepatobiliary disease has been investigated. A modified GLC method was used, with an overall coefficient of variation of +/- 11% in the control range. Serum was obtained after a 12 hour fast, and two hours after a fatty meal from 73 patients and 14 control subjects. In controls the total fasting SBA of 2.17 +/- 0.86 mumol/l increased significantly (p less than 0.001) to 3.81 +/- 1.14 mumol/l after a meal. All icteric patients had raised SBA, but in 23 anicteric patients there was no significant difference in the detection of chronic liver disease by fasting SBA, postprandial SBA, AST, or gamma GTP. Compared with controls, serum in patients contained proportionately less deoxycholic acid (p less than 0.001), there was proportionately more cholic acid in extrahepatic obstruction (p less than 0.001), and proportionately more chenodeoxycholic acid in patients with cirrhosis, viral hepatitis, and neoplasia (p less than 0.001). In control subjects, the fasting cholic:chenodeoxycholic acid ratio ranged from 0.5-1.0, and differed significantly (p less than 0.001) from patients with extrahepatic obstruction 0.96-3.6, and cirrhosis 0.1-0.5. It is concluded that serum bile acids measured by sensitive methods can provide useful diagnostic information.

Fasting serum levels of total 3 alpha-hydroxy bile acids were measured in 163 consecutive patients, who clinically were suspected of having a hepatobiliary disorder. By means of routine biochemical liver tests and paraclinical investigations the clinical suspicion was confirmed in 95 patients and disproved in the other 68 patients. A comparison between this diagnostic grouping and the serum bile acids levels showed that the predictive value of serum concentrations above a discrimination value of 10 mumol/l--that is, the predictive value of a positive test--was 1.0 (0.94-1.0), whereas the corresponding predictive value of a negative test was 0.66 (0.56-0.75). Thus, fasting serum levels of total 3 alpha-hydroxy bile acids may be used as a highly specific and moderately sensitive diagnostic test for hepatobiliary disorders. Furthermore, the study showed that the nosographic sensitivity of total 3 alpha-hydroxy bile acids in patients with verified cirrhosis was significantly greater than that of serum bilirubins and not significantly different from those of the other routine biochemical liver tests.

Cholylglycin (CG-) and SLCG levels were measured in patients with various biopsy-confirmed liver and bile disease. SLCG values were found to be more sensitive, and to distinguish clearly between steatosis hepatis and normals, as well as between cirrhosis hepatis, with and without, portal hypertension. Correlations between the common liver tests and the SLCG levels were poor, but a clear distinction was possible between the various histologically defined liver diseases. The paper concludes with a description of a new method of stimulating the SLCG values, intravenously. Using this method, it is possible to keep consumption of material and time and incommodities inflicted to the patient, as low as possible. Nevertheless staging of parenchymatous liver diseases, is feasible.

The clinical usefulness of measuring serum bile acid concentrations as a diagnostic test for hepatobiliary disease was examined in 80 cats that were suspected of having hepatic disease. Serum values of total bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) also were measured. Fasting serum bile acid values were determined by use of solid-phase radioimmunoassay for total conjugated bile acids or by a direct enzymatic spectrophotometric method. A definitive diagnosis was established by histologic examination of the liver, and on the basis of these findings, cats were assigned to groups (1 to 8, respectively) including: extrahepatic bile duct obstruction, hepatic lipidosis, cirrhosis, intrahepatic cholestasis (cholangiohepatitis, cholangitis), neoplasia, hepatic necrosis, portosystemic vascular anomalies, and miscellaneous. Cats in group 8 had no morphologic evidence of hepatobiliary disease or had hepatic lesions that were mild. Test efficacy of fasting serum bile acids, total bilirubin, ALP, ALT, and AST were expressed by use of 4 indices: sensitivity, specificity, positive predictive value, and negative predictive value. The diagnostic efficacy of fasting serum bile acids was examined alone and in combinations with the other tests. There was wide overlapping of values of fasting serum bile acids, total bilirubin, ALP, ALT, and AST among cats in groups 1 to 7. The specificity of fasting serum bile acids for the diagnosis of hepatic disease exceeded 90% at values greater than or equal to 5 mumol/L and reached 100% at greater than or equal to 15 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to evaluate the clinical diagnostic value of serum total bile acid (STBA) in hepatobiliary diseases. Fasting STBA was measured using the enzymatic colorimetric method in 44 normal control cases and 153 cases of hepatobiliary disease, and then abnormal rates were compared to other conventional liver function tests. These 153 cases of hepatobiliary diseases included acute viral hepatitis (10 cases), chronic persistent hepatitis (32 cases), chronic active hepatitis (16 cases), liver cirrhosis (15 cases), alcoholic hepatitis (11 cases), alcoholic fatty liver (23 cases), alcoholic cirrhosis (17 cases), chronic liver diseases with slight fatty changes (10 cases) and hepatocellular carcinoma (6 cases). Except for 8 cases of acute viral hepatitis, the above cases were verified by liver biopsy. There were also 13 cases of biliary tract diseases. Fasting STBA and other conventional liver function tests were used in the above hepatobiliary diseases during the acute, exacerbated or decompensated stage, and the stable or compensated stage, and their abnormal rates compared. The results of this study revealed that the concentration of STBA is raised in various hepatobiliary diseases, which is related to the degree of hepatic cell injury and the various stages of liver. The concentration of STBA was higher in the acute, exacerbated or decompensated stage than in the convalescent, stable or compensated stage of liver diseases. When the abnormal rates of STBA were compared to other conventional liver function tests, the abnormal rates of STBA were not inferior to r-GT, GOT and GPT, and were more accurate than the other liver function tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum bile acid patterns were determined in 31 infants ranging in age from 4 days to 24 weeks. Fifteen infants with extrahepatic biliary atresia had a mean concentration of serum bile acids of 90 microng/ml +/- 47 SD;; 16 infants with neonatal hepatitis had a mean concentration of 60 +/- 35.5 SD. The chenodeoxycholate/cholate ratio was greater than one in 13 infants (87%) with atresia and in 10 infants (66%) with neonatal hepatitis. Except for the tendency of a higher total concentration of serum bile acids in infants with atresia, a single serum bile acid value does not differentiate neonatal hepatitis from extrahepatic biliary atresia. The high proportion of chenodeoxycholate in extrahepatic atresia is different from the pattern in other types of cholestatic disease and may reflect an underlying hepatitis.

An enzymatic-fluorimetric method using a highly purified 3alpha-hydroxysteroid dehydrogenase (Sterognost-3alpha, Nyco) was used to determine fasting serum bile acid concentrations on 49 occasions in 43 patients with various liver diseases. A two-hour postprandial bile acid determination was carried out on 29 occasions in 27 of the patients. Fasting bile acid concentration correlated significantly both in cholestatic hepatobiliary and in parenchymatous liver disease to serum bilirubin and aspartate aminotransferase (ASAT) but not to alanine aminotransferase (ALAT), alkaline phosphatase, or albumin. The two-hour postprandial bile acid concentration was above normal in all patients with biochemical and/or histological signs of hepatobiliary disease, also when fasting concentration was within normal limits. In parenchymatous liver disease correlations existed between the two-hour postprandial bile acid concentration and bilirubin, ASAT, and ALAT. The sensitivity of serum bile acid estimation was compared to other liver function tests. Both the fasting and the postprandial serum bile acid concentrations tended to be more sensitive tests of hepatobiliary disease than bilirubin, ASAT and ALAT.

The diagnostic value of determining total conjugated serum bile acid (SBA) concentrations was evaluated in fasting dogs with spontaneous liver disease. Conjugated primary SBA values were determined by radioimmunoassay in 12 healthy dogs, 64 dogs with hepatobiliary disease, and 9 dogs with intestinal disorders unassociated with clinical or biochemical evidence of liver disease. Reference values for SBA concentrations ranged from 0 to 5 mumol/L and were not significantly different from those determined in dogs with intestinal disease (P less than 0.05). Mean SBA concentrations determined in dogs with portosystemic shunts, glucocorticoid-induced hepatopathy, hepatic neoplasia, hepatitis, cholestasis, and cirrhosis were significantly greater than reference values (P less than 0.05). The mean SBA concentration in dogs with glucocorticoid-induced hepatopathy was significantly (P less than 0.05) lower than that in all other clinical groups of dogs with liver disease, except in dogs with cholestasis. Although these 2 groups were statistically indistinguishable, dogs with glucocorticoid-induced hepatopathy generally had lower SBA values (2 to 37 mumol/L) than did the group with cholestasis (2 to 562 mumol/L). The SBA concentrations in fasting dogs were weakly correlated with histologic evidence of hepatic damage, as determined by a total biopsy score (r = 0.28, P less than 0.02). Because total SBA concentrations were increased in 89% of all dogs with hepatobiliary disease, the determination of SBA appears to be a sensitive test of hepatic dysfunction.

Serum bile acids have been measured in patients with a wide variety of liver diseases using a technique which separates the major individual conjugated and free bile acids. Total serum bile acids may be elevated up to 100 times the normal concentration in patients with liver disease and this increase consists largely of conjugated bile acids. The ratio of glycine-conjugated to taurine-conjugated bile salts is low in all types of liver disease and this is found particularly in the serum of patients with obstructive jaundice. There is a decrease in the ratio of trihydroxy:dihydroxy cholanic acid in patients with cirrhosis.