Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs

Portosystemic shunting occurs frequently either as congenital anomalies of the portal vein (PVA) or as acquired shunting (AS) due to portal hypertension secondary to parenchymal liver disease or portal vein thrombosis. The 2 most commonly used screening tests for portosystemic shunting are bile acid and plasma ammonia concentrations. The purpose of this study was to compare the 12-hour fasting plasma ammonia (AMM) and bile acid concentration (BA) as tests for diagnosing portosystemic shunting. Medical records of 337 dogs were used in which AMM and BA were measured simultaneously and in which portosystemic shunting was confirmed or excluded. These dogs were divided into 2 groups (group 1: portosystemic shunting present, n = 153, and group 2: portosystemic shunting absent, n = 184). Group 1 was subdivided into 2 subgroups (group 1a: PVA, n = 132 and group 1b: AS, n = 21). The sensitivity of AMM in detecting PVA was 100% and of BA was 92.2%. For portosystemic shunting in general (PVA or AS), the sensitivity of AMM was 98% and that of BA was 88.9%. The specificity in the total population of AMM was 89.1% and that of BA was 67.9%. If only dogs with liver diseases were included with (n = 153) or without (n = 28) shunting, the specificity of AMM to detect shunting was 89.3% and that of BA was 17.9%. In conclusion, AMM is a highly sensitive and specific parameter to detect PVA and portosystemic shunting in a general population and in dogs with liver disease, whereas BA is somewhat less sensitive and considerably less specific.     

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)     

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 as an indicator of liver disease in dogs

Total serum bile acids were determined in 62 dogs with different primary or secondary liver diseases, using 3α-hydroxysteroid dehydrogenase coupled to nitrobluetetrazolium in a centrifugal analyzer. A reaction time of 4 min was sufficient, yielding a within run coefficient of variation of 7% at 6 µmol/1 and 3% at 27 µmol/1. A reference range of 0–4.4 µmol/1 2 h post prandially was observed. The sensitivity of bile acids as a liver function test was superior to that of alanine and aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase and combinations of two of these. The bile acids test detected 36 of 39 patients with a morphological or clinical liver diagnosis. For dogs with heart failure the bile acids test was a markedly more sensitive indicator of secondary liver involvement than alanine aminotransferase or alkaline phosphatase. For secondary liver affections associated with pyometra or epilepsy medication the opposite was the case. Bile acid values in the pooled patient material was not correlated to any of the 4 enzymes measured. For cirrhosis there was positive correlation, however, with the amino transferase values.     

Plasma amino acid analysis in dogs with experimentally induced hepatocellular and obstructive jaundice

Plasma amino acid concentrations were determined weekly for 4 weeks in 6 sham-operated control dogs, in 6 sham-operated dogs after induction of liver disease with dimethylnitrosamine (DMNA), and in 6 dogs after surgical ligation of the common bile duct. Results were compared with standard biochemical indices of liver function and with histologic changes in serial liver biopsy specimens. Concentrations of most amino acids increased after 2 weeks in DMNA-treated dogs, whereas they were normal or decreased in bile duct-ligated dogs. With increasing severity of the liver disease, the molar ratio (normal mean +/- SEM = 3.48 +/- 0.14) in DMNA-treated dogs decreased to 2.42 +/- 0.19 by 2 weeks and to 1.17 +/- 0.09 by 4 weeks. The ratio remained normal in bile duct-ligated dogs. Molar ratio and aromatic amino acid concentrations correlated better with hepatic necrosis and inflammation than did standard biochemical indices (eg, bilirubin, liver enzymes). Therefore, plasma amino acid analysis and determination of the molar ratio may be useful in the differential diagnosis of hepatocellular and obstructive jaundice in dogs. A decrease in the molar ratio may reflect portal hypertension and hepatocellular disease.     

Serum bile acids and the assessment of hepatic function in dogs and cats

Current literature in veterinary internal medicine regarding the clinical use of the serum bile acids test to assess hepatobiliary function in dogs and cats is reviewed. The test is best used in cases where clinical signs and routine laboratory tests are suggestive of liver disease. It is a highly sensitive and specific test of hepatic function, and is the best method of assessing liver function available to the private practitioner. Abnormal results do not determine etiology, severity, or prognosis of the disorder. They merely indicate the need for hepatic biopsy. The serum bile acids concentration should always be measured in both a fasting and a two-hour postprandial sample.     

A screening test for subclinical liver disease in horses affected by pyrrolizidine alkaloid toxicosis

Objective: To evaluate various biochemical tests as indicators of subclinical liver disease in horses exposed to pyrrolizidine alkaloid toxicosis.
Design: A clinical pathology field study.
Animals: Twenty-two clinically normal horses from four properties in the Kimberley region of Western Australia.
Procedure: Serum samples from each horse were assayed for gamma glutamyltransferase, alkaline phosphatase and aspartate aminotransferase activities, and for serum bile acid concentration, albumin and total protein. Serum protein electrophoresis was performed and their amino acid profiles determined. Bromosulphophihalein halfclearance times were measured. Horses were then subjected to a single liver biopsy. Results were analysed by, variance of group means, the Fisher-Irwin exact test, and by sensitivity and specificity calculation.
Results: Horses were classified into 2 groups, of 10 unaffected and 12 subclinically affected, on the basis of liver histology. Significant differences between the unaffected and subclinical groups were observed for gamma glutamyltransferase and alkaline phosphatase activities (P < 0.01). Gamma glutamyltransferase had sufficient sensitivity (75%) and specificity (90%) to function as a primary screening test for subclinical liver disease in horses exposed to pyrrolizidine alkaloids. Alkaline phosphatase was useful, but with lower sensitivity (58%).
Conclusion: Serum gamma glutamyltransferase activity is a useful screening test for detecting subclinical liver disease in horses exposed to pyrrolizidine alkaloids under field conditions in northern Australia.     

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)     

Detection of serum alpha-fetoprotein in dogs with hepatic tumors.

Serum alpha-fetoprotein (AFP) concentration was detected by use of 2 commercially available kits containing antibodies to human AFP--a radioimmunoassay and an enzymetric test. Using neonatal canine serum (a source high in AFP), it was determined that reagents from both kits were able to bind to canine AFP, but a significant difference was detected in AFP concentration. The enzymetric test was superior in detecting canine AFP. Sera from dogs were classified into 6 groups: from dogs with primary hepatic tumors only (group 1); from dogs with primary hepatic tumors and other tumors (group 2); from dogs with normal liver but with other types of neoplasia (group 3); from dogs with nonneoplastic hepatic disease and tumors originating in other organs (group 4); from dogs with nonneoplastic hepatic disease only (group 5); and from clinically normal dogs (group 6). Serum biochemical determinations (alkaline phosphatase, alanine transaminase, albumin, total protein, total bilirubin, and serum bile acids) and values from the 2 AFP assays were obtained for all dogs. Serum AFP concentration detected by the enzymetric test was significantly higher in dogs with hepatocellular carcinoma and cholangiocarcinoma. Values greater than 250 ng/ml were detected in 5 of 9 dogs with cholangiocarcinoma and in 3 of 4 dogs with hepatocellular carcinoma. High serum AFP concentration also was indicative of liver involvement in 2 of 3 dogs with primary hepatic lymphosarcoma; 2 dogs had values greater than 225 ng/ml. Serum AFP concentration in dogs with other types of hepatic tumors was less than 250 ng/ml, and serum AFP concentration could not be correlated with such tumors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uric acid and phosphorus excretion in dogs with lymphosarcoma

Serum uric acid and phosphorus concentrations were determined for 27 dogs with multicentric lymphosarcoma before and after chemotherapy. Mean serum uric acid values in dogs before treatment were significantly higher (P less than 0.05) than those of a control group of healthy dogs. Serum uric acid values did not change after treatment. Of the 27 dogs, 13 had 24-hour urine collections to determine endogenous creatinine clearance and quantitation of uric acid and phosphorus excretion before and after treatment for lymphosarcoma. Mean values for 24-hour creatinine clearance before and after treatment were statistically similar in dogs with lymphosarcoma, although the values were lower than those in a normal range. Total urinary phosphorus excretions were increased significantly (P less than 0.01) after treatment without change in fractional excretion. Chemotherapeutic agents used accounted for the significant (P less than 0.05) increase in urine volume after treatment and may have affected the excretion of uric acid and phosphorus. Seemingly, dogs with uncomplicated lymphosarcoma rarely have renal dysfunction or clinically important alterations in uric acid or phosphorus excretion secondary to rapid tumor lysis. However, preexisting renal disease or systemic complications, such as hypercalcemia, may be associated with increased risk of further renal impairment during treatment.     

Liver disease in dogs with tracheal collapse

BACKGROUND: Hepatopathy in dogs with chronic respiratory diseases is poorly recognized. The aim of this study was to evaluate liver parameters alanine transferase, alkaline phosphatase, and glutamate dehydrogenase, as well as basal and stimulated bile acid concentration, in dogs with tracheal collapse. HYPOTHESIS: Dogs with tracheal collapse have hepatopathy. ANIMALS: 26 dogs with tracheal collapse. MATERIALS AND METHODS: Gall bladder contraction was stimulated by intramuscular injection of a synthetic cholecystokinin analogue (ceruletide). Twelve healthy Beagle dogs and 30 dogs of various breeds investigated previously without evidence of hepatic, gastrointestinal, or respiratory diseases served as control. Amelioration of liver variables was assessed after stent implantation. RESULTS: Twelve of 26 (46%) dogs had increased serum activity of 2 or more liver enzymes. Serum basal bile acid concentrations were high in 24 of 26 dogs. Twenty- and 40-minute stimulated bile acids were significantly higher in dogs with tracheal collapse (64.2 +130.0/-43.0 micromol/L and 82.6 +164.0/-57.1 micromol/L) compared to the control dogs (7.0 +/- 3.6 micromol/L and 6.4 +/- 3.5 micromol/L). All twelve dogs reevaluated after a median of 58 days (48-219 days) had a normal breathing pattern and significantly decreased 20 and 40 minutes stimulated bile acids (50.0 +92.7/-32.8 micromol/L, 52.8 +97.6/-34.3 micromol/L; P = .0043), whereas plasma liver enzyme activities were not significantly influenced. CONCLUSION AND CLINICAL IMPORTANCE: There was a significant hepatic dysfunction in the majority of dogs with a tracheal collapse. Liver function should be routinely assessed in dogs with severe respiratory disease.     

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.     

Post-prandial serum bile acid concentrations and ammonia tolerance in Maltese dogs with and without hepatic vascular anomalies

SUMMARY: Post-prandial serum bile acid concentrations were measured in 200 Maltese dogs in an attempt to identify those with subclinical portosystemic shunts. Five of these were later shown to have hepatic pathology or abnormal liver function. In the other 195 Maltese bile acid concentrations ranged from 1 to 362 μmol.L^-1 (mean ± SD, 70 ±50 μmol.L^-1; median, 65.0 μmol.L^-1). Of these, 79% were above the reference range (0 to 31 μmol.L^-1) established from 23 mixed-breed control dogs. It was therefore not possible to determine the prevalence of subclinical portosystemic shunts on the basis of bile acid determinations.
Further investigation of liver function was performed to investigate why bile acid concentrations were increased in these dogs. Rectal ammonia tolerance tests were normal in 102 of 106 Maltese tested and liver samples (11 dogs) and plasma biochemistry profiles (9 dogs) demonstrated no significant hepatic disease or dysfunction.
Of 2 Maltese with hyperammonaemia after administration of ammonium chloride, one had a large congenital portosystemic shunt that was confirmed at surgery. In the other there were no macroscopic portosystemic communications, but a liver biopsy showed histological changes consistent with microscopic portovascular dysplasia.
Total serum bile acid concentrations were consistently lower when assessed by highperformance liquid chromatography than by an enzymatic spectrophotometric method. This discrepancy was substantially larger in Maltese than in control dogs, suggesting the presence of an additional reacting substance in the serum of Maltese dogs.     

Evaluation of urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in dogs

OBJECTIVE: To evaluate 3 methods for measuring urine bile acids (UBA) and compare their diagnostic performance with that of the serum bile acids (SBA) test and other routine screening tests in dogs with hepatic disorders. DESIGN: Prospective study. ANIMALS: 15 healthy dogs, 102 dogs with hepatic disorders, and 9 dogs with clinical signs of hepatic disorders that were found to have nonhepatic disorders. PROCEDURES: Blood and urine samples were collected from sick dogs and healthy dogs for serum biochemical analyses, and determination of concentrations of SBA and UBA. Urine samples were obtained from 15 healthy dogs to establish an upper cutoff value for UBA concentrations. The UBA were measured by use of a quantitative-linked enzymatic colorimetric method. Three analytical modifications were evaluated; 1 quantified only urine sulfated bile acids (USBA), 1 only urine nonsulfated bile acids (UNSBA), and 1 quantified both (USBA plus UNSBA). The UBA values were standardized with the urine creatinine concentration. RESULTS: The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio tests had the best diagnostic performance of the UBA tests; each had a substantially higher specificity, slightly higher positive predictive value, slightly lower negative predictive value, and lower sensitivity than the SBA test. These UBA-to-creatinine values were positively correlated with SBA values. The USBA-to-creatinine ratio had poor sensitivity, indicating a low rate of bile acid sulfation in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The UBA can be measured in dogs with sufficient repeatability and accuracy for clinical application. The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio identified dogs with hepatic disorders nearly as well as the SBA test.     

Evaluation of serum L-phenylalanine concentration as indicator of liver disease in dogs: a pilot study

Because essential amino acids are metabolized in the liver, liver diseases may impair their catabolism. In this study, serum L-phenylalanine concentrations in 28 dogs with liver diseases were compared with those of 28 healthy dogs and 13 dogs with nonhepatic diseases. Dogs with liver diseases had significantly increased L-phenylalanine serum concentrations compared to healthy dogs (P<0.001) and to those with nonhepatic diseases (P<0.01). There were no significant differences among the L-phenylalanine serum concentrations of dogs with different degrees of liver diseases. The sensitivity and specificity of L-phenylalanine to fasting bile acids were comparable.     

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.     

Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary disease in dogs

A postprandial ammonia tolerance test (PPATT) was performed on normal dogs and dogs with signs that suggested they may have liver disease. All dogs underwent transcolonic scintigraphy, liver biopsy, or both and were assigned to extrahepatic disease, primary hepatocellular, and congenital portosystemic vascular anomalies (PSVA) groups. Each dog was fed a chicken and rice diet providing 25% of its estimated daily metabolizable energy requirement (MER) as an ammonia challenge. This is practical in patients with liver disease because ammonium chloride administration often causes vomiting or ammonia toxicity. Venous ammonia concentrations were measured before feeding and every 2 hours after feeding for 8 hours. No difference in mean ammonia concentrations between dogs with extrahepatic disease and control dogs was found. Therefore, the specificity of the PPATT was 100%. Dogs with hepatocellular disease showed no change in mean ammonia concentration at any time point, before or after feeding, but sensitivity was greatest when venous ammonia was measured 6 hours after feeding (sensitivity before feeding, 28%, and after feeding, 36%). Among dogs with congenital PSVA, mean ammonia concentrations were higher than the reference range at all time points before and after feeding, and peak mean ammonia concentration occurred 6 hours after feeding. In this group, the sensitivity of the PPATT was 81% before feeding and 91% 6 hours after feeding. This study demonstrates that the measurement of venous ammonia concentration is a useful test to detect congenital PSVA, and the sensitivity of the test may be improved by sampling 6 hours after feeding. The PPATT has poor sensitivity in detecting primary hepatocellular disease.     

Changes in the concentrations of bile acids in the plasma of sheep with liver damage

The concentration of total plasma bile acids was measured in normal sheep and in sheep in which liver damage was induced by chronic copper poisoning, ligated bile ducts or induced ketosis. All three treatments produced a rise in total bile acid concentration in plasma which was proportional to the degree of hepatic damage seen histologically and which tended to parallel changes in activity of iditol, and glutamate dehydrogenase and aspartate amino-transferase in plasma. Plasma bile acid concentration was a more sensitive method of detecting these types of liver damage than was the measurement of total plasma bilirubin concentration, and could be used to assess alterations in liver function in sheep.     

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.     

Congenital dilatation of the bile ducts (Caroli's disease) in young dogs

We describe 8 young dogs with congenital dilatation of the intra- and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed-breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids: increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra- and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein-restricted diet.