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 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.     

Lack of associations between ultrasonographic appearance of parenchymal lesions of the canine liver and histological diagnosis

Objective: To assess if there are any ultrasonographic features that may enable tentative diagnosis of hepatic parenchymal disease. Methods: Records of 371 dogs that had abdominal ultrasonography and abnormal liver on biopsy or necropsy were reviewed. Results: Histological diagnoses were hepatitis (n=77), nodular hyperplasia (n=47), vacuolar change (n=45), fibrosis (n=32), primary hepatic carcinoma (n=30), lymphoma (n=28), metastatic neoplasia (n=27), necrosis (n=21), lipidosis (n=17), haemangiosarcoma (n=13), round cell tumour (n=9), hepatocellular adenoma (n=8), degenerative change (n=6), steroid hepatopathy (n=7) and extramedullary haematopoiesis (n=4). The most prevalent ultrasonographic features were multifocal lesions (63% livers with haemangiosarcoma and 43% livers with hepatocellular carcinoma), diffuse lesions (71% livers with steroid hepatopathy, 44% livers with fibrosis and 40% livers with vacuolar hepatopathy), hyperechoic lesions (71% livers with steroid hepatopathy, 41% livers with lipidosis and 38% livers with fibrosis), heterogeneous lesions (62% livers with haemangiosarcoma), hepatomegaly (43% livers with steroid hepatopathy) and peritoneal fluid (62% livers with haemangiosarcoma). Target lesions were associated with malignancy in 67% instances. Marked variability in ultrasonographic appearance of lesions was observed for all diagnoses, and no statistically significant associations between ultrasonographic appearance and diagnosis were found. Clinical Significance: Histological examination remains essential for diagnosis of canine hepatic disease.     

Diagnostic value of serum gamma-glutamyl transferase and alkaline phosphatase activities in hepatobiliary disease in the cat

The diagnostic value of serum gamma-glutamyl transferase (GGT) activity and serum alkaline phosphatase (ALP) activity in the detection of liver disease in the cat (n = 69) was compared. On the basis of histologic examination of the liver, cats were assigned to 8 groups: group 1--complete extrahepatic bile duct obstruction (n = 5), group 2--cholangiohepatitis-cholangitis syndrome (n = 11), group 3--hepatic lipidosis (n = 15), group 4--neoplasia, including lymphosarcoma and myeloproliferative disease (n = 9), group 5--hepatic necrosis (n = 7), group 6--cirrhosis (n = 3), group 7--portosystemic vascular anomaly (n = 4), and group 8--miscellaneous (n = 15). Cats assigned to group 8 lacked substantial histologic abnormalities of the liver. The mean value +/- SD of GGT in 20 clinically normal cats was 0.44 +/- 0.26 IU/L. The highest GGT activity in clinical patients developed in groups 1, 2, and 6. The highest ALP activity developed in groups 1 to 4. Significant correlations between GGT and ALP activities were detected only in groups 2 (P less than 0.001) and 5 (P less than 0.10). Among 54 cats with hepatic disease, only 11% had both the GGT and ALP activities within the normal ranges. Comparatively, 52% had ALP activities within the normal range, and 17% had GGT activities within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effect of age on liver enzyme activities in serum of healthy quarter horses

Serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), 5'nucleotidase (5'NT), sorbitol dehydrogenase (SDH), and aspartate transaminase activities were measured in 10 clinically healthy foals, 10 yearlings, and 10 two-year-old Quarter Horses. Enzyme activities in foals at 0.5 to 3 days, 2 to 3 weeks, and 5 to 7 weeks of age were compared with enzyme activities from yearling and 2-year-old horses. Multivariate analyses of variance revealed significantly higher enzyme values in foals (P less than 0.002). This increase was mainly a result of higher ALP and GGT activities, with lesser effects due to higher SDH and 5'NT activities. Standard deviations for ALP and GGT were also larger in foals than in adult horses. The wide variation of ALP and GGT activities may limit their usefulness in the diagnosis of hepatic disease in foals. Standard deviations for serum AST, SDH, and 5'NT activities were smaller. These enzymes may be indicators of hepatobiliary disease in foals. The high serum enzyme activities in healthy foals may reflect a physiologic difference between foals and adult horses. Relative hepatic mass (as a percentage of body weight) and enzyme activity per gram of hepatic tissue are high in young animals, indicating that the high serum enzyme activities in foals are due partly to a high rate of enzyme production and release.     

Alterations in selected serum biochemical constituents in equids after induced hepatic disease

Effects of induced cholestasis and hepatocellular necrosis and of fasting on serum biochemical constituents including bile acids, IgA, bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), arginase, and the clearance of sodium sulfobromophthalein were studied in 4 groups of equids. The reference value for serum bile acids, as determined by an enzymatic colorimetric procedure for horses and ponies was 5.94 +/- 2.72 mumol/L, there being no statistical difference for horses and ponies. Sample collection at time of feeding had no effect on serum bile acid concentration. Seemingly, serum bile acids, arginase, and GGT were the most sensitive indicators of cholestasis and/or hepatocellular necrosis and would form an essential minimum effective battery of tests to diagnose and prognose hepatic disease in equids. These tests provided a measure of hepatobiliary transport function (bile acids), cell necrosis (arginase), and cholestasis (GGT and bile acids).     

Effect of colostrum ingestion on gamma-glutamyltransferase and alkaline phosphatase activities in neonatal pups.

Analysis of hepatic enzyme activities in serum samples from 1- to 3-day-old pups revealed alkaline phosphatase (ALP) activities that were 30 times higher and gamma-glutamyltransferase (GGT) activities that were 100 times higher than activities in clinically normal adult dogs. A study was conducted to investigate high enzyme activity in pups and to determine whether there is any association between serum enzyme activity and colostrum ingestion, passive transfer of maternal serum enzyme (in colostrum or in utero), or excessive renal or hepatic tissue enzymes. Serum enzyme activity was quantified in 15 neonatal pups before and after ingestion of colostrum and in 3 colostrum-deprived neonates fed a milk substitute. Serum samples were collected on postpartum days 0, 1, 10, 15, and 30. Enzyme activity was also quantified in serum from pregnant and lactating bitches (collected on days -2, 0, 1, 10, 30), hepatic and renal tissue from clinically normal adult dogs and 1-day-old pups, colostrum, milk (collected on days 10 and 30), and milk replacer. Significant (P less than 0.01) differences in serum GGT and ALP activities between colostrum-deprived and suckling pups did not exist before initial feeding. Significant (P less than 0.001) increases in serum GGT and ALP activities developed within 24 hours in suckling pups, but not in the colostrum-deprived pups. At 10 and 30 days after birth, serum GGT and ALP activities were less than values before suckling in all pups. Enzyme activities in bitches' serum remained within the normal range for adult dogs throughout whelping and lactation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Hepatic effects of halothane, isoflurane or sevoflurane anaesthesia in dogs

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty-one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between 13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre-anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12-14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre-medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.     

Diagnosis and prognosis of chronic hepatitis and cirrhosis in dogs

The purpose of this investigation was to evaluate the significance of enzymatic and biochemical analyses in the classification of chronic inflammatory liver disease and to evaluate the prognosis of these diseases. Chronic hepatitis and cirrhosis were diagnosed by histopathological examination in 79 dogs. Decreased appetite and lethargy were the most common owner complaints (46/79). Vomiting and, or, diarrhoea were reported in 27/79 dogs. Ascites was the most common clinical sign (43/79), whereas icterus was a more unusual finding demonstrated in 16/79 dogs. Liver cirrhosis was diagnosed most frequently, in 33/79 dogs, followed by chronic progressive hepatitis (22/79), chronic cholangiohepatitis (13/79), and chronic non-specific hepatitis (11/79). Hypoalbuminaemia was the most consistent biochemical aberration in liver cirrhosis (25/26) and in chronic progressive hepatitis (13/18). These diseases also showed normal to mildly increased concentrations of serum alanine aminotransferase (ALT) and serum γ-glutamyl transferase (GGT) and a moderate to marked increase of serum alkaline phosphatase (ALP) and fasting serum bile acid (SBA) concentrations. As expected, icterus and markedly elevated ALT, ALP, GGT and SBA levels were demonstrated in chronic cholangiohepatitis. In this disease hypoalbuminaemia was shown in 6/12 dogs, whereas in dogs with chronic non-specific hepatitis, mean SBA and albumin concentrations were normal. In liver cirrhosis the prognosis was poor, with 94 per cent of the dogs dead within one week of established diagnosis. For dogs with the other types of chronic hepatitis the prognosis was more favourable with the mean survival time ranging from 21-1 to 36-4 months.     

Copper-associated liver disease in Dalmatians: a review of 10 dogs (1998-2001)

This retrospective study summarizes 10 Dalmatians suspected of having hepatic copper toxicosis. Hepatic copper toxicosis can result from either a primary metabolic defect in hepatic copper metabolism or from altered hepatic biliary excretion of copper. An inherited copper-associated hepatopathy has been documented in Bedlington Terriers, and there is evidence for familial copper-associated liver disease in West Highland White (WHW) Terriers and Skye Terriers. Nine of the 10 Dalmatians in this study presented for gastrointestinal clinical signs, including anorexia and vomiting. All animals had increased alanine aminotransferase (ALT) enzyme activity, and 9 of 10 had increased alkaline phosphatase (ALP) enzyme activity. The relative increase in ALT activity was much greater than the relative increase in ALP activity, suggesting a predominantly hepatocellular rather than cholestatic liver disease. The mean hepatic copper concentration for 9 Dalmatians was 3,197 microg/g dry weight liver (dwl) (normal, <450 microg/g). In 5 of these 9 dogs, hepatic copper concentrations exceeded 2,000 microg/g dwl. Necroinflammatory alterations associated with copper-laden parenchymal cells were the notable histopathologic finding. The inflammatory infiltrate was either primarily lymphocytic or neutrophilic. Morphologic features of cholestasis generally were not prominent except in those dogs with severe pathology. These findings lend support to the hypothesis that a primary metabolic defect in hepatic copper metabolism occurs in the Dalmatian breed. The mechanism and genetic basis of this condition require further study.     

Chronic hepatitis in Labrador Retrievers: clinical presentation and prognostic factors

BACKGROUND: An increased incidence of chronic hepatitis has been reported in Labrador Retrievers. HYPOTHESIS: A breed associated hepatopathy occurs in Labrador Retrievers. ANIMALS: Twenty-four client-owned Labrador Retrievers. METHODS: Medical records of dogs with histopathologic confirmation of chronic hepatitis were retrospectively reviewed. A clinical score based on clinical signs and the results of biochemical tests was generated for each dog. Hepatic biopsy specimens were scored for disease activity, fibrosis, and copper accumulation. RESULTS: The median age was 9.3 years (range, 3.9-14.0 years). Clinical signs included inappetence, vomiting, lethargy, and weight loss. All dogs had increases in serum activity of one or more hepatobiliary enzyme. Hyperbilirubinemia and hypoalbuminemia were present in 45% and 21% of dogs, respectively. The median clinical score was 2.9, with a range of 0-8. The median histopathology activity and the fibrosis scores were 3.5 (range, 1-6) and 3.0 (range, 0-4), respectively. Rhodanine-positive copper staining was present in 15 of 17 biopsy specimens, with a median score of 2.0 (range, 0-3). Median survival was 374 days (range, 1-2645 days). A prolonged prothrombin time (P = .013) and thrombocytopenia (P = .041) were associated with survival < 2 months. The presence of anorexia (P = .049), hypoglobulinemia (P = .045), or prolonged partial thromboplastin time (P = .033) were associated with shorter overall survival times. The clinical score correlated with survival time (P = .030) and histopathologic staging (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE: A progressive hepatopathy in Labrador Retrievers in this study was marked by chronic inflammation, fibrosis, and copper accumulation. A clinical scoring system that correlates with survival time may be useful as a noninvasive method to predict prognosis.     

Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis

Plasma amino acid concentrations were measured in 36 dogs diagnosed with superficial necrolytic dermatitis (SND) via skin biopsy. The median age of the dogs was 10 years, and 27 out of 36 (75%) were male. Twenty-two out of 36 (61%) of the dogs were accounted for by six breeds; West Highland white terriers (six), Shetland sheepdogs (five), cocker spaniels (four), Scottish terriers (three), Lhasa apsos (two) and Border collies (two). The mean concentration (+/- standard deviation) was calculated for each measured plasma amino acid and compared to previously documented concentrations of plasma amino acids measured in dogs with acute and chronic hepatitis. The ratio of branched chain amino acids to aromatic amino acids in the dogs with SND was 2.6, slightly lower than that in normal dogs. The mean plasma amino acid concentrations for dogs with SND were significantly lower than for dogs with acute and chronic hepatitis. A metabolic hepatopathy in which there is increased hepatic catabolism of amino acids is hypothesized to explain the hypoaminoacidaemia seen in SND.     

Evaluation of the bromosulfophthalein 30-minute retention test for the diagnosis of hepatic disease in dogs

The purpose of this study was to evaluate efficacy of bromosulfophthalein (BSP) retention testing in dogs with and without histopathologically confirmed hepatobiliary disease. Medical records of 150 dogs with hepatobiliary disease having both a BSP test and hepatic biopsy were retrieved. Histopathologic slides of liver tissue were reviewed, and dogs were classified according to 1 of 11 histopathologic categories. Twenty-five clinically normal random-source dogs were used as controls for hepatic biopsy and BSP testing. No dogs suffered adverse effects due to BSP administration. BSP retention was significantly (P < .05) higher in hospitalized (13.9%) than control (3.2%) dogs, but the test could not distinguish between hospitalized dogs with different types of hepatobiliary disease. Sensitivity, specificity, and predictive values of BSP retention as a test for hepatic disease were calculated. Using 5.0% as a cutoff for normal BSP retention resulted in a specificity of 88% and a sensitivity of 76%. Using 6.0% as a cutoff for normal BSP retention resulted in a specificity of 100% and a sensitivity of 70%. Dogs of this study having BSP retention of >6% had at least an 86% chance of having an abnormal liver. We concluded that continued use of BSP retention testing is warranted as a noninvasive diagnostic test for liver disease in dogs.     

Effects of long-term phenobarbital treatment on the liver in dogs

Long-term administration of phenobarbital has been reported to cause hepatic injury in dogs. Phenobarbital induces hepatic enzymes, and it may be difficult to distinguish the effect of enzyme induction on serum liver enzyme activities from actual hepatic damage. The hepatotoxicity of phenobarbital and the impact of enzyme induction on serum liver enzyme activity were investigated prospectively in 12 normal dogs. Phenobarbital was administered for 29 weeks at 5 mg per kilogram of body weight (range, 4.8— 6.6 mg/kg) PO q12h, resulting in therapeutic serum phenobarbital concentrations (20–40 μg/mL). Serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), fasted bile acids (fBA), total bilirubin, and albumin were determined before and during treatment. Lateral abdominal radiographs, abdominal ultrasounds, and histopathologic examinations of liver tissue obtained by ultrasound-guided biopsy were performed before and during treatment. Radiographs revealed a moderate increase in liver size in most dogs. Ultrasonographic examination revealed no change in liver echogenicity or architecture. No evidence of morphologic liver damage was observed histopathologically. ALP and ALT increased significantly ( P < .05), GGT increased transiently, and albumin decreased transiently during the study. There were no significant changes in AST, bilirubin, and fBA. These results suggest that increases in serum ALP, ALT, and GGT may reflect enzyme induction rather than hepatic injury during phenobarbital treatment in dogs. Serum AST, fBA, and bilirubin, and ultrasonographic evaluation of the liver are not affected by the enzyme-inducing effect of phenobarbital and can therefore be helpful to assess liver disease in dogs treated with the drug.     

Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration

Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T4) concentrations in some dogs. The duration of liver enzyme induction and T4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T4 (TT4), free T4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.     

Hepatobiliary Scintigraphy in the Evaluation of Feline Liver Disease

Hepatobiliary scintigraphy (HBS) was performed in 10 cats with histologically documented hepatobiliary disease. The scintigraphic patterns were classified into one of 5 categories: normal, primary hepatocellular dysfunction, primary in-trahepatic cholestasis, mixed hepatocellular and intrahe-patic cholestasis, and extrahepatic obstructive patterns. Initial attempts were made to correlate specific disease entities with HBS patterns, but a consistent relationship could not be determined. A correlation between the histological severity of a given hepatic disease and the HBS pattern was made. All cats (n = 5) with a mixed hepatocellular and intra-hepatic cholestasis scintigraphic pattern with normal gallbladder function had a histologically severe form of their individual hepatic disease. Three of the 4 cats with an intra-hepatic cholestasis pattern and normal hepatocellular and gallbladder function had histologically mild or moderate forms of their individual hepatic disease. One cat had an extrahepatic obstructive pattern where no radiopharmaceu-tical was identified in the gallbladder or small intestine by 3 hours postinjection. This study suggests that HBS can be useful in cats with hepatobiliary disease to assess the severity of hepatic dysfunction, and to determine if extrahepatic biliary obstruction is present. Correlation between HBS patterns and specific disease entities such as hepatic lipidosis or cholangitis-cholangiohepatitis syndrome could not be made in this study.     

Diagnostic evaluation of canine serum alkaline phosphatase by immunochemical means and interpretation of results.

Sera of several canine patients contained an isoenzyme of alkaline phosphatase (ALP) that resembled intestinal ALP with respect to heat inactivation, L-phenylalanine inhibition, and sensitivity to anti-canine intestinal ALP antibody, but differed with regard to the electrophoretic migration. The electrophoretic mobility of the isoenzyme was slightly cathodal than that of hepatic ALP, and its migration was reduced, similar to that of hepatic isoenzyme after neuraminidase treatment. This isoenzyme, which could be corticosteroid induced, was in the sera of numerous dogs with hepatobiliary disorders and was different from the hepatic isoenzyme that appeared in the sera of dogs with acute hepatitis, based on anti-canine intestinal ALP antibody interaction, heat inactivation, and electrophoretic migration.     

Incidence of hepatopathies in dogs administered zonisamide orally: A retrospective study of 384 cases

BackgroundAcute hepatopathy secondary to administration of zonisamide has been reported in 2 dogs, but overall incidence of hepatopathy is unknown.ObjectiveTo characterize the incidence of hepatopathy in dogs administered zonisamide PO.AnimalsThree hundred eighty‐four dogs administered zonisamide PO.MethodsMulticenter retrospective study. Medical records were searched for dogs prescribed zonisamide PO and which had follow‐up for at least 3 months (acute exposure) and >3 months (chronic exposure). Reported clinical signs, physical examination findings, and serum biochemical panels were reviewed for possible hepatotoxicosis. Serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity and albumin concentration were documented for all available cases.ResultsAcute clinical hepatopathy was found in 2 of 384 treated dogs (0.52%, 95% confidence interval [CI], 0.06‐1.9) after 13‐16 days of zonisamide treatment. One additional dog had elevated serum ALT activity with no clinical signs. Of these 3 dogs, 2 recovered after administration of zonisamide was stopped, and 1 was euthanized because of liver failure. Of the 117 cases chronically administered zonisamide, 10 had an increase in ALP, 6 had an increase in ALT, and 1 had hypoalbuminemia. No clinical signs of liver disease were noted in dogs chronically treated with zonisamide (median, 20 months; range, 5‐94 months).Conclusions and Clinical ImportanceAcute, potentially life‐threatening hepatopathy associated with oral administration of zonisamide to dogs is estimated to occur in less than 1% of dogs and was observed in the first 3 weeks of treatment. Subclinical abnormalities in ALT and ALP activity were noted in <10% of dogs during chronic administration of zonisamide, with no clinical signs of liver disease noted.