Urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in cats

Urine bile acid (UBA) tests reflecting "average" serum bile acid (SBA) concentrations may have greater practical utility than paired SBA samples in cats. This study evaluated whether urine sulfated bile acids (USBAs), urine nousulfated bile acids (UNSBAs), or a combined approach had a clinical utility equivalent to SBAs. Routine serum biochemistry tests, SBA concentrations, and urine samples were collected from 54 cats with hepatobiliary disease, 17 cats with nonhepatic disorders, and 8 healthy cats. UBAs were measured by a quantitative enzymatic colorimetric method, and results were normalized with urine creatinine (UCr) concentrations. Significantly higher values occurred in cats with liver disease than in cats without liver disease for USBA : UCr, UNSBA:UCr, and (USBA and UNSBA) : UCr, P < .05 each. UBA tests with diagnostic performance (sensitivity [SS], specificity [SP], and positive and negative predictive values [PV+ and PV-]) equivalent to SBAs were the UNSBA : UCr and the combined test (SS: 87, 87 versus 85; SP: 88, 88 versus 88; PV+: 96, 96 versus 96; PV-: 68, 65 versus 68; UNSBA : UCr, [USBA, and UNSBA]: UCr versus SBA, respectively). Clinical applications of the UNSBA : UCr or the combined (USBA and UNSBA) : UCr test should be useful as convenient diagnostic tests for identifying cats with liver disease and high SEA concentrations.     

Determination of serum bile acids in fasting dogs with hepatobiliary disease

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.     

Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs

In samples collected from 170 dogs suspected of having hepatobiliary disease, preprandial serum bile acids (PRSBA) and postprandial serum bile acids (POSBA) concentrations were measured, using a spectrophotometric enzymatic method. Dogs were assigned to 8 disease groups and 1 control group on the basis of hepatic histopathologic findings. Pre- and postprandial SBA concentrations and results of routine biochemical analyses (including total bilirubin, albumin, and BUN concentrations, and serum alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) activities) were expressed, using 4 indices: sensitivity, specificity, positive predictive value, and negative predictive value. Single tests and combinations of tests in series were evaluated. For diagnosis of hepatobiliary disease, the specificity of PRSBA was 100% at values greater than 20 mumol/L and of POSBA was 100% at values greater than 25 mumol/L. Test combinations with the best sensitivity for diagnosing the following diseases were: PRSBA-POSBA for cirrhosis, portosystemic vascular anomaly, and glucocorticoid hepatopathy; PRSBA-POSBA or PRSBA-ALP for cholestasis; PRSBA-POSBA or ALT-AST for chronic hepatitis; PRSBA-ALT for hepatic necrosis and passive congestion; and PRSBA-ALP for neoplasia. Test combinations with the overall highest sensitivity and positive predictive value for the fewest number of tests were PRSBA-POSBA, and either PRSBA or POSBA combined with an enzyme activity (ALT, AST, or ALP). The overall test efficacy for PRSBA vs POSBA was nearly identical: for PRSBA, it was 82.4%, and for POSBA, it was 82.3%. On the basis of the results of this study, PRSBA greater than 20 mumol/L or POSBA greater than 25 mumol/L (measured by use of an enzymatic procedure) indicates histopathologic abnormalities of the hepatobiliary system or portosystemic vascular anastomosis. Seemingly, determination of SBA concentrations can be used to indicate the propriety for hepatic biopsy. Pre- and postprandial serum bile acids concentrations should be evaluated in conjunction with routinely used hepatobiliary screening tests for best diagnostic advantage.     

Comparison of postprandial and ceruletide serum bile acid stimulation in dogs

BACKGROUND: Postprandial (PP) serum bile acid (SBA) stimulation is an important test for detecting hepatic dysfunction in dogs. However, this test is influenced by numerous variables, and a standardized approach using an injectable cholecystokinin analog (ceruletide) may be advantageous. HYPOTHESIS: Ceruletide SBA stimulation test is more sensitive than PP SBA stimulation in dogs. ANIMALS: Animals with portosystemic shunt (PSS) (n = 11) and dogs with upper respiratory disease (URD) (n = 9) were investigated. Healthy dogs (n = 13) and dogs with other diseases (n = 17) served as controls. METHODS: All dogs underwent SBA stimulation with food and ceruletide. Stimulation blood samples were drawn at 60/120 minutes and 20/30/40 minutes, respectively. Results were compared statistically, and the sensitivity and specificity were determined with receiver-operating characteristic curves. RESULTS: Stimulated SBA were significantly higher in both study groups than in controls. For dogs with PSS, the sensitivity and specificity (>35 micromol/L) were 100% postprandially (120 minutes) and 91 and 100%, respectively, postceruletide (30 minutes). The difference between these values was not statistically significant. For dogs with URD, the sensitivity and specificity (>22 micromol/L) were 44 and 88% postprandially (120 minutes) and 100 and 88% postceruletide (30 minutes). CONCLUSIONS AND CLINICAL IMPORTANCE: Ceruletide SBA stimulation circumvents exogenous and endogenous influences associated with PP SBA stimulation. The results indicate that ceruletide SBA stimulation performs as well as PP SBA stimulation in dogs with PSS and is more sensitive for the detection of hepatic dysfunction in dogs with URD.     

Effect of oral ursodeoxycholic acid on bile acids tolerance tests in healthy dogs

OBJECTIVE: To determine whether oral administration of ursodeoxycholic acid (UDCA) to healthy dogs alters the results of the bile acids tolerance test. METHODS: UDCA (15 mg/kg once daily) was administered to 16 healthy dogs for 7 days. Health of the dogs was assessed by clinical examination, haematology, serum biochemistry and a bile acids tolerance test. Normal liver structure was confirmed by histopathology at the end of the study. Bile acids tolerance tests were performed before and at the end of the treatment period, with each dog serving as its own control. For the posttreatment bile acids tolerance test, UDCA was administered at the time of feeding. RESULTS: Pretreatment, the fasted serum total bile acid concentrations ranged between 0 and 9 micromol/L. In the majority of dogs, the postprandial total bile acid concentration was greater than the preprandial value, with a range of 0 to 16 micromol/L. The fasted total bile acid concentration was 0 micromol/L in most dogs (93.75%) after treatment with UDCA. Postprandial serum bile acids also remained within the reference range for the majority of dogs (93.75%) after UDCA treatment. A single dog had a postprandial bile acid concentration above the reference range, but the concentration was within the reference range when the assay was repeated the following day without concurrent administration of UDCA. The pre- and postprandial total serum bile acid concentrations were not significantly affected by UDCA treatment. CONCLUSION: The administration of UDCA does not alter the bile acids tolerance test of normal healthy dogs.     

Serum bile acids concentrations in healthy and clinically ill neonatal foals

BACKGROUND: Reference ranges for serum bile acids (SBA) concentration are well established in healthy adult horses. Increased values are indicative of hepatic disease. HYPOTHESES: SBA concentrations are significantly greater in the neonatal period compared with mature horses, and illness in the neonatal period will further increase SBA. ANIMALS: Ten healthy mature horses, 12 healthy foals, and 31 clinically ill foals. METHODS: Prospective cross-sectional study. Blood samples were obtained once from the mature horses, from healthy foals immediately after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of age; and from ill foals less than 1 month of age at the time of admission to the Veterinary Teaching Hospital. SBA concentrations were determined enzymatically and by radioimmunoassay. Total and direct bilirubin and triglyceride concentrations were measured, as well as sorbitol dehydrogenase (SDH) and gamma-glutamyltransferase (GGT) activities. RESULTS: There was a significant negative correlation between age and SBA concentration. Compared with mature horses, SBA concentrations were significantly greater in healthy foals at each collection time over the first 6 weeks of life. Radioimmunoassay values were lower than enzymatic SBA values, with increasing bias as the mean difference between values increased. When comparing age-matched values between healthy and ill foals, there were no significant differences in SBA. None of the ill foals had a primary diagnosis of hepatic disease. There was no significant correlation between the SBA concentration and the bilirubin or triglyceride concentrations or the GGT activity. There was a significant direct correlation between increased SBA and serum SDH activity in healthy foals only. CONCLUSION AND CLINICAL IMPORTANCE: SBA concentrations in foals are significantly higher in the early neonatal period, underscoring the importance of using age-matched references when evaluating clinical pathology values during the neonatal period.     

Liver glutathione concentrations in dogs and cats with naturally occurring liver disease

OBJECTIVE: To determine total glutathione (GSH) and glutathione disulfide (GSSG) concentrations in liver tissues from dogs and cats with spontaneous liver disease. SAMPLE POPULATION: Liver biopsy specimens from 63 dogs and 20 cats with liver disease and 12 healthy dogs and 15 healthy cats. PROCEDURE: GSH was measured by use of an enzymatic method; GSSG was measured after 2-vinylpyridine extraction of reduced GSH. Concentrations were expressed by use of wet liver weight and concentration of tissue protein and DNA. RESULTS: Disorders included necroinflammatory liver diseases (24 dogs, 10 cats), extrahepatic bile duct obstruction (8 dogs, 3 cats), vacuolar hepatopathy (16 dogs), hepatic lipidosis (4 cats), portosystemic vascular anomalies (15 dogs), and hepatic lymphosarcoma (3 cats). Significantly higher liver GSH and protein concentrations and a lower tissue DNA concentration and ratio of reduced GSH-to-GSSG were found in healthy cats, compared with healthy dogs. Of 63 dogs and 20 cats with liver disease, 22 and 14 had low liver concentrations of GSH (micromol) per gram of tissue; 10 and 10 had low liver concentrations of GSH (nmol) per milligram of tissue protein; and 26 and 18 had low liver concentrations of GSH (nmol) per microgram of tissue DNA, respectively. Low liver tissue concentrations of GSH were found in cats with necroinflammatory liver disease and hepatic lipidosis. Low liver concentrations of GSH per microgram of tissue DNA were found in dogs with necroinflammatory liver disease and cats with necroinflammatory liver disease, extrahepatic bile duct occlusion, and hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: Low GSH values are common in necroinflammatory liver disorders, extrahepatic bile duct occlusion, and feline hepatic lipidosis. Cats may have higher risk than dogs for low liver GSH concentrations.     

Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog

The clinical usefulness of measuring serum bile acid concentrations as a diagnostic test for hepatobiliary disease, was examined in 150 dogs that were suspected of having hepatic disease. Serum values of total bilirubin (TB), alkaline phosphatase (ALP), alanine transaminase (ALT), and albumin were also measured. Fasting serum bile acid (FSBA) values were determined, using a solid-phase radioimmunoassay for total conjugated bile acids or a direct enzymatic spectrophotometric method. A definitive diagnosis was established by histologic examination of the liver. On the basis of histologic findings, dogs were assigned to groups (1 to 8, respectively) including: extrahepatic bile duct obstruction, cirrhosis, portal systemic vascular anastomosis (PSVA), hepatic necrosis, intrahepatic cholestasis, steroid hepatopathy, neoplasia, and secondary disease. Dogs in group 8 had no morphologic evidence of hepatobiliary disease or had mild hepatic lesions. Test efficacies of FSBA, TB, ALP, ALT, and albumin were expressed using 4 indices: sensitivity, specificity, and positive-predictive and negative-predictive values. The diagnostic efficacy of FSBA was examined alone and in combinations with the other tests. There was wide overlapping of FSBA values among dogs in groups 1 to 7, and there was wide overlapping of ALT and ALP values among dogs in all groups. The specificity of FSBA for the diagnosis of liver disease exceeded 90% at values greater than or equal to 30 mumol/L and reached 100% at greater than or equal to 50 mumol/L. Individual liver tests with the best sensitivity for each group were:FSBA and ALP for extrahepatic bile duct obstruction; FSBA for cirrhosis and PSVA; ALT for hepatic necrosis; and ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Combinations of tests with the best sensitivity for each group were: FSBA + ALP for extrahepatic bile duct obstruction; FSBA + ALT for cirrhosis and PSVA; FSBA + ALT and TB + ALT for hepatic necrosis; and FSBA + ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Individual tests had the best sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of serum bile acid concentrations for the diagnosis of portosystemic venous anomalies in the dog and cat

The serum concentration of bile acids was measured in dogs and cats with portosystemic venous anomalies (PSVA). In 14 dogs, the mean serum bile acid concentration after 12 hours of fasting was 61.7 +/- 68.7 mumol/L (normal, 2.3 +/- 0.4 mumol/L (SEM) and when measured 2 hours after a meal in 15 dogs was 229.9 +/- 87.7 mumol/L (normal, 8.3 +/- 2.2 mumol/L). The fasting serum bile acid concentration was within the normal range in 5 of 14 dogs. The postprandial concentration was determined in 3 of the 5 and in each case increased more than tenfold above the fasting value. The mean fasting serum bile acid concentration in 4 cats was 24.4 +/- 10.1 mumol/L (normal, 1.7 +/- 0.3 mumol/L) and in 2 of the cats increased to a mean of 120.6 mumol/L (normal, 8.3 +/- 0.8 mumol/L) 2 hours after feeding. The bile acid values in patients with PSVA were correlated with values for blood ammonia content, sulfobromophthalein (BSP) retention, and results of conventional tests of hepatic function. Bile acid concentrations were more sensitive than abnormalities in serum enzyme activities or BSP retention and equal in sensitivity to the ammonia tolerance test in detecting hepatobiliary insufficiency. Bile acid measurements were accomplished with less inconvenience to the patient and clinician, than tests of BSP excretion or ammonia tolerance. Used in combination with conventional laboratory tests for hepatic disease, pre- and postprandial serum bile acid concentrations appear to be a sensitive and specific indicator of hepatobiliary dysfunction of value in the diagnosis of PSVA in the dog and cat.     

Urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs.

A urine cortisol:creatinine (c:c) ratio, determined from a free-catch morning sample, was evaluated in each of 83 dogs as a screening test for hyper-adrenocorticism. The dogs evaluated were allotted to 3 groups, including 20 healthy dogs, 40 dogs with confirmed hyperadrenocorticism (HAC), and 23 dogs with polyuria and polydipsia not attributable to HAC (polyuria/polydipsia group; PU/PD). Overlap in the urine c:c ratios (mean +/- SEM), comparing results from the healthy dogs (5.7 x 10(-6) +/- 0.9) with those from the HAC dogs (337.7 x 10(-6) +/- 72.0) was not found. However, 11 (64%) of the 18 values from the PU/PD dogs (42.6 x 10(-6) +/- 9.4) were above the lowest ratio in the HAC group and 50% of the HAC group had a urine c:c ratio below the highest value in the PU/PD group. When the mean urine c:c ratio (+/- 2 SD) for the group of healthy dogs was used as a reference range, 100% of the HAC dogs and 18 (77%) of 23 dogs in the PU/PD group had abnormal urine c:c ratios. The sensitivity of the urine c:c ratio to discriminate dogs with HAC was 100%. The specificity of the urine c:c ratio was 22% and its diagnostic accuracy was 76%. On the basis of our findings, a urine c:c ratio within the reference range provides strong evidence to rule out HAC. However, abnormal urine c:c ratios are obtained from dogs with clinical diseases other than HAC. Therefore, measurement of a urine c:c ratio should not be used as the sole screening test to confirm a diagnosis of HAC.     

Bile acid concentrations in the diagnosis of hepatobiliary disease in the cat

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)     

Evaluation of plasma protein C activity for detection of hepatobiliary disease and portosystemic shunting in dogs

OBJECTIVE: To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs. DESIGN: Prospective study. ANIMALS: 238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS. PROCEDURES: Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity. RESULTS: Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC > or = 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC. CONCLUSIONS AND CLINICAL RELEVANCE: Combining PC with routine tests improved recognition of PSS, hepatic failure, and severe hepatobiliary disease and signified a grave prognosis when coupled with hyperbilirubinemia and low antithrombin activity in hepatic failure. Protein C activity can help prioritize tests used to distinguish PSVA from MVD and sensitively reflects improved hepatic-portal perfusion after PSVA ligation.     

Evaluation of the association between microalbuminuria and the urine albumin-creatinine ratio and systemic disease in dogs

OBJECTIVE: To evaluate semiquantitative and quantitative assays for microalbuminuria and determination of the urine albumin-creatinine (UAC) ratio in detection of systemic disease in dogs without overt proteinuria. DESIGN: Prospective study. ANIMALS: 408 dogs. PROCEDURES: Urine samples that had been obtained from dogs for which a complete medical record was available and in which results of a dipstick test for urine protein were negative were evaluated. Urine protein-creatinine ratios (cutoff values, 0.5 and 0.1), semiquantitative and quantitative microalbuminuria values (cutoff value, 1 mg/dL), and UAC ratios (cutoff values, 100 and 200 mg/g) were determined. Clinical diagnoses rendered within 3 months of enrollment in the study were recorded. Sensitivity and specificity were determined with disease status serving as the standard. Associations with clinical diagnosis, sex, age, BUN and serum creatinine concentrations, blood pressure, results of bacterial culture of urine, temperature, pyuria, hematuria, and bacteriuria were evaluated by use of logistic regression analysis. RESULTS: 48 dogs were healthy, and 360 had at least 1 disease. Significant associations were detected between age, presence of disease, presence of neoplastic disease, BUN and serum creatinine concentrations, and hematuria and results of 1 or both of the microalbuminuria assays. CONCLUSIONS AND CLINICAL RELEVANCE: Microalbuminuria was associated with underlying disease. The sensitivity and specificity of the semiquantitative microalbuminuria test for detection of systemic disease were superior to those of other tests. Microalbuminuria testing in conjunction with other screening procedures may increase diagnosis of subclinical disease, but a prospective study in which the predictive values of screening tests are evaluated, with and without microalbuminuria determination, is needed.     

Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats

Background: Portosystemic shunt (PSS) is the most common cause of hepatic encephalopathy in dogs and cats. Fasting ammonia and serum bile acids (SBA) are used to diagnose PSS, but their true sensitivity and specificity have not been fully evaluated, especially in cats. Objectives: The purpose of this study was to determine the diagnostic accuracy of fasting ammonia and SBA concentrations in the diagnosis of PSS in dogs and cats and to compare diagnostic accuracy between species. Methods: A retrospective analysis of data from 373 dogs and 85 cats presented to the clinic from 1996 to 2006 was carried out. Based on clinical, laboratory, and imaging findings, animals were grouped as having PSS, parenchymal hepatic disease, or extrahepatic disease. The sensitivity and specificity of ammonia and SBA concentrations for the diagnosis of PSS were calculated and receiver‐operating characteristic analysis was used to optimize cut‐offs. Results: Using the upper limit of laboratory reference intervals (ammonia, 59 μmol/L; SBA, 20 μmol/L), the sensitivity and specificity of ammonia was 85% and 86% in dogs, and 83% and 76% in cats, respectively. The sensitivity and specificity of SBA was 93% and 67% in dogs, and 100% and 71% in cats, respectively. Using optimal cut‐off points for ammonia (dogs, 57 μmol/L; cats, 94 μmol/L) the sensitivity and specificity was 91% and 84% in dogs and 83% and 86% in cats, respectively. Using optimal cut‐off points for SBA (dogs, 58 μmol/L; cats, 34 μmol/L) the sensitivity and specificity was 78% and 87% in dogs and 100% and 84% in cats. Conclusion: Increased fasting ammonia and SBA concentrations are accurate indicators of PSS. An improvement in diagnostic accuracy can be achieved by using defined optimal cut‐off points for the selective diagnosis of PSS.     

Serum bile acid analysis in dogs with experimentally induced cholestatic jaundice

Serum bile acid (SBA) concentration was determined weekly for 4 weeks in dogs with experimentally induced hyperbilirubinemic liver disease. Obstructive jaundice was created in 6 dogs by surgical ligation of the common bile duct, and hepatocellular jaundice was created in 6 sham-operated dogs by administration of dimethylnitrosamine; 6 other sham-operated dogs served as controls. Serum bile acid concentration increased rapidly after bile duct ligation (from 0.6 +/- 0.1 to 69.2 +/- 15.3 mumol/L at 3 days), peaked at 14 days (247.8 +/- 54.1 mumol/L), and then gradually decreased (179.9 +/- 27.1 mumol/L at 28 days). Serum bile acid concentration in dimethylnitrosamine-treated dogs increased more gradually to 38.9 +/- 10.7 mumol/L at 28 days, at which time the serum bilirubin concentration was comparable with that of bile duct-ligated dogs. Mean total SBA values in bile duct-ligated dogs were significantly (P less than 0.01) higher than those in control and dimethylnitrosamine-treated dogs at days 3 through 28, with no overlap of individual values. Serum bile acid concentration at day 28 correlated positively (P less than 0.01) with cholestasis and bile duct proliferation observed in liver biopsy specimens, but did not correlate with necrosis or inflammation. Serum bile acid concentration also correlated positively (P less than 0.01) with serum bilirubin and cholesterol concentrations and with serum alkaline phosphatase and alanine transaminase activities. Results of the study reported here indicated a relationship between SBA concentration and cholestasis in dogs; extrahepatic bile duct obstruction resulted in the highest SBA values.(ABSTRACT TRUNCATED AT 250 WORDS)     

The utility of uric acid assay in dogs as an indicator of functional hepatic mass

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.     

Fast resolution of hypercortisolism in dogs with portosystemic encephalopathy after surgical shunt closure

The aim of this study was to investigate whether hypercortisolism in dogs with congenital portosystemic shunts disappeared after surgical closure of the shunts concomitantly with recovery from hepatic encephalopathy. We examined 22 dogs before and four weeks after partial surgical closure of a single, large congenital portosystemic shunt (PSS). Parameters measured to characterise the basal activity of the pituitary-adrenal axis were the cortisol:creatinine (c/c) ratio in home-sampled urine and total and free cortisol in plasma. The binding characteristics of cortisol binding globulin (CBG) in pooled pre- and postoperative plasma were also determined. Ammonia and bile acid concentrations were measured in plasma to characterise the liver perfusion and function. Clinical symptoms relevant to liver function, cortisol excess, and hepatic encephalopathy were recorded semiquantitatively using a standardized questionnaire. The dogs had hypercortisolism before surgery, which had normalized four weeks later. The pre- and postoperative concentrations (means +/- SEM) were, respectively, 238+/-45 nM and 126+/-19 nM for total cortisol, 15.5+/-2.6 nM and 8.4+/-1.3 nM for free cortisol in plasma, 13.4+/-4.3 x 10(-6) and 3.9+/-0.4 x 10(-6) for c/c in urine. The pre- and postoperative Bmax values of CBG were 41 and 79, and Kd values were 3.8 and 5.5. The concentrations of ammonia were 217+/-23 microM and 32+/-3.1 microM, and of bile acids 1 10+/-33 and 11.1+/-2.0 microM, respectively. We conclude that there is a close relation between portosystemic encephalopathy and hypercortisolism in dogs with PSS and that both deviations resolve completely within four weeks of closure of the shunt.     

Evaluation of total serum bile acid concentrations for the diagnosis of hepatobiliary disease in cattle.

Serum bile acid concentrations were measured in 41 clinically healthy cattle of different breeds. There was no diurnal variation in values and age and sex had no effect. There was no significant difference between serum and plasma bile acid concentrations in clinically healthy cattle. Serum bile acids were stable on storage at -20 degrees C. The total serum bile acid concentrations, together with other tests of hepatic disease, were evaluated in cattle with various types of hepatobiliary disease (hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi, fascioliasis), respiratory, cardiovascular and infectious diseases, and in various other conditions not affecting the liver. Total serum bile acids were the most specific and sensitive indicators of a wide variety of hepatic diseases and were significantly correlated with the degree of clinical illness.     

Results of surgical management of portosystemic shunts in dogs: 20 cases (1985-1990).

Serum bile acid (SBA) values were obtained in 20 dogs, 2.5 to 60 months (mean, 18.6 months) after surgery for occlusion of a congenital portosystemic shunt. The SBA values obtained after food was withheld were significantly (P < 0.005) reduced at follow-up, compared with preoperative values. In 85% of the dogs (17/20), response to surgery was graded by the owners as excellent or good, although most dogs had abnormal SBA values at follow-up. Significant difference in clinical results or follow-up SBA values was not found in dogs that had complete or partial occlusion of the shunting vessel. Correlation between clinical results and SBA values also was not detected. Dogs that were > 2 years old at the time of diagnosis and surgery had a significantly (P = 0.012) poorer clinical result than that of dogs < 1 year old.     

Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987-1997)

OBJECTIVE: To determine usefulness of the test for proteins induced by vitamin K absence or antagonism (PIVKA) to identify anticoagulant-poisoned dogs, compared with one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT) tests. DESIGN: Retrospective study. ANIMALS: 325 dogs. PROCEDURE: Comparisons of results of PIVKA, OSPT, and APTT measurements in dogs with anticoagulant poisoning, hepatic disease, disseminated intravascular coagulation, other blood-related disorders, immune-mediated diseases, or other chronic and acute diseases were performed. Median, quartile, and range values were determined. RESULTS: PIVKA tests with a 150-second critical value had > 98% specificity and > 90% sensitivity for diagnosis of anticoagulant poisoning versus > 99% specificity and > 79% sensitivity with a 300-second critical value. Comparison of PIVKA values among diagnostic groups revealed significant differences between dogs with anticoagulant poisoning and all other groups. CONCLUSIONS AND CLINICAL RELEVANCE: The PIVKA test with a 150-second critical value is diagnostically useful for distinguishing anticoagulant poisoning from other coagulopathies. Severe liver disease can cause false-positive results. Administration of vitamin K1 or early evaluation (within a few hours of ingesting anticoagulant) may cause false-negative results. Dogs with PIVKA test values > 150 seconds and clinical signs of anticoagulant poisoning can confidently be considered to have anticoagulant poisoning because of the high test sensitivity and specificity.