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
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
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
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. (J Am Vet Med Assoc 2003;222:
Objective—To compare morphologic diagnoses determined
from needle biopsy specimens obtained from
the livers of dogs and cats with morphologic diagnoses
determined from wedge biopsy specimens.
Animals—124 dogs and cats.
Procedure—2 needle biopsy specimens were
obtained from each animal; wedge biopsy specimens
were obtained from the same liver lobe during laparotomy
or postmortem examination. Histologic features
were scored independently by 3 individuals; a morphologic
diagnosis was rendered after histologic features
were scored. Cases were included only if at least 2 of
the 3 examiners agreed on the morphologic diagnosis;
the definitive diagnosis was considered to be the morphologic
diagnosis rendered for the wedge biopsy
specimen. Physical characteristics (length, width, surface
area, degree of fragmentation, and number of portal
triads for needle biopsy specimens and surface area
for wedge biopsy specimens) were determined.
Results—Definitive diagnoses included hepatic necrosis
(n = 10), cholangitis-cholangiohepatitis (13), chronic
hepatitis-cirrhosis (12), canine vacuolar hepatopathy
(11), portosystemic vascular anomaly-microvascular
dysplasia (17), neoplasia (10), miscellaneous hepatic
disorders (18), and no hepatic disease (33). For individual
examiners, the morphologic diagnosis assigned
to needle biopsy specimens agreed with the morphologic
diagnosis assigned to wedge biopsy specimens
for 56 and 67% of the specimens. All 3 examiners
agreed on the morphologic diagnosis assigned to needle
and wedge biopsy specimens for 44 and 65% of
the specimens, respectively. Morphologic diagnoses
assigned to needle biopsy specimens concurred with
the definitive diagnosis for 59 of 124 (48%) animals.
Conclusions and Clinical Relevance—Results
suggest that needle biopsy specimens of the liver
from dogs and cats must be interpreted with caution.
(J Am Vet Med Assoc 2002;220:1483–1490)
Objective—To determine risk, clinical features, and treatment responses for gallbladder disorders in Shetland Sheepdogs.
Design—Retrospective case-control study.
Animals—38 Shetland Sheepdogs with gallbladder disease.
Procedures—Medical records were reviewed for signalment, history, physical findings, laboratory results, imaging features, coexistent illnesses, histologic findings, treatments, and survival rates.
Results—Mature dogs with gastrointestinal signs were predisposed (odds ratio, 7.2) to gallbladder disorders. Gallbladder mucocele was confirmed in 25 dogs. Concurrent problems included pancreatitis, hyperlipidemia, corticosteroid excess, hypothyroidism, protein-losing nephropathy, diabetes mellitus, cholelithiasis, and gallbladder dysmotility. Mortality rate was 68% with and 32% without bile peritonitis. Nonsurvivors had high WBC and neutrophil count and low potassium concentration. Although preprandial hypercholesterolemia, hypertriglyceridemia, and high serum liver enzyme activities were common, gallbladder disease was serendipitously discovered in 11 of 38 dogs. Histologic examination (n = 20 dogs) revealed gallbladder cystic mucosal hyperplasia in 20 dogs, cholecystitis in 16, periportal hepatitis in 9, and vacuolar hepatopathy in 7. Surgery included cholecystectomy (n = 17) and cholecystoenterostomy (4). In 1 hyperlipidemic dog without clinical signs, gallbladder mucocele resolved 6 months after beginning use of a fat-restricted diet and ursodeoxycholic acid.
Conclusions and Clinical Relevance—Shetland Sheepdogs are predisposed to gallbladder disorders, with mucoceles and concurrent dyslipidemia or dysmotility in many affected dogs. Most dogs were without clinical signs during mucocele development. Low survival rate after cholecystectomy in clinically affected dogs suggested that preemptive surgical interventions may be a more appropriate treatment strategy.
Objective—To evaluate the influence of treatment with ultralow-dose aspirin (ULDAsp) on platelet aggregation, P-selectin (CD62P) expression, and formation of platelet-leukocyte aggregates in clinically normal dogs.
Animals—18 clinically normal dogs.
Procedures—Studies were conducted before and 24 hours after ULDAsp administration (0.5 mg/kg, PO, q 24 h, for 2 days). Whole blood impedance aggregometry for the assessment of platelet function was performed with sodium citrate–anticoagulated blood and aggregation agonists (ADP at 20, 10, and 5 μmol/L; collagen at 10, 5, and 2 μg/mL). Onset, maximum response, and rate of platelet aggregation were recorded. Flow cytometric assays were configured to detect thrombin-induced CD62P expression and platelet-leukocyte aggregates in EDTA-anticoagulated whole blood. Externalized platelet CD62P and constitutive CD61 (GPIIIa) were labeled with antibodies conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively. Red blood cell–lysed paraformaldehyde-fixed EDTA-anticoagulated whole blood was dual labeled with CD61-FITC and a panleukocyte antibody (CD18-PE) to characterize platelet-leukocyte aggregates.
Results—ULDAsp significantly delayed platelet aggregation onset with ADP at 20 μmol/L by 54% to 104%, attenuated maximum aggregation with various concentrations of ADP and collagen by ≥ 41%, and slowed aggregation rate with the highest ADP and collagen concentrations by ≥ 39%. Depending on the parameter tested, up to 30% of dogs failed to have an ULDAsp effect. Thrombin stimulation significantly increased CD62P expression in platelets and platelet-leukocyte aggregates, but ULDAsp did not alter basal or thrombin-stimulated CD62P expression.
Conclusions and Clinical Relevance—ULDAsp treatment of clinically normal dogs impaired platelet aggregation in most dogs, but did not influence CD62P platelet membrane expression. (Am J Vet Res 2010;71:1294–1304)
Objective—To characterize signalment, clinical features, clinicopathologic variables, hepatic ultrasonographic characteristics, endocrinologic profiles, treatment response, and age at death of Scottish Terriers with progressive vacuolar hepatopathy (VH) with or without hepatocellular carcinoma (HCC).
Design—Retrospective case series.
Animals—114 Scottish Terriers with progressive VH.
Procedures—Electronic databases from 1980 to 2013 were searched for adult (age > 1 year) Scottish Terriers with histopathologic diagnoses of diffuse glycogen-like VH. Available sections of liver specimens were histologically reevaluated to confirm diffuse VH with or without HCC; 8 dogs with HCC only had neoplastic tissue available. Physical examination, clinicopathologic, treatment, and survival data were obtained.
Results—39 of 114 (34%) dogs with VH had HCC detected at surgery or necropsy or by abdominal ultrasonography. Histologic findings indicated that HCC was seemingly preceded by dysplastic hepatocellular foci. No significant differences were found in clinicopathologic variables or age at death between VH-affected dogs with or without HCC. Fifteen of 26 (58%) dogs with high hepatic copper concentrations had histologic features consistent with copper-associated hepatopathy. Although signs consistent with hyperadrenocorticism were observed in 40% (46/114) of dogs, definitive diagnosis was inconsistently confirmed. Assessment of adrenal sex hormone concentrations before and after ACTH administration identified high progesterone and androstenedione concentrations in 88% (22/25) and 80% (20/25) of tested dogs, respectively.
Conclusions and Clinical Relevance—Results suggested that VH in Scottish Terriers may be linked to adrenal steroidogenesis and a predisposition to HCC. In dogs with VH, frequent serum biochemical analysis and ultrasonographic surveillance for early tumor detection are recommended.
OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS).
ANIMALS 20 client-owned dogs of various breeds and ages.
PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values.
RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline.
CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.
OBJECTIVE To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome.
DESIGN Retrospective case series.
ANIMALS 31 Shih Tzus.
PROCEDURES Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed.
RESULTS There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months).
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS. (J Am Vet Med Assoc 2016;248:802–813)
Objective—To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease.
Design—Retrospective cross-sectional study.
Animals—100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction , cholangitis-cholangiohepatitis , and miscellaneous hepatobiliary disorders ) and 14 cats without hepatobiliary disease.
Procedures—From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH.
Results—Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of > 700 μg/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia.
Conclusions and Clinical Relevance—Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.
Objective—To characterize clinical signs, clinicopathologic features, treatments, and survival in dogs with naturally acquired foodborne aflatoxicosis.
Design—Retrospective case series.
Animals—72 dogs that consumed aflatoxin-contaminated commercial dog food.
Procedures—Medical records of affected dogs were reviewed. Between December 2005 and March 2006, dogs were identified as having foodborne aflatoxin hepatotoxicosis on the basis of the history of consumption of contaminated food or characteristic histopathologic lesions (subject dog or a recently deceased dog in the same household or kennel). Recorded information included signalment, clinical features, clinicopathologic test results, treatments, and survival. Data were analyzed by survival status.
Results—Most dogs were of large breeds from breeding kennels. No significant differences were found in age or weight between 26 (36%) survivor dogs and 46 (64%) nonsurvivor dogs. Severity of clinical signs varied widely; 7 dogs died abruptly. In order of onset, clinical features included anorexia, lethargy, vomiting, jaundice, diarrhea (melena, hematochezia), abdominal effusion, peripheral edema, and terminal encephalopathy and hemorrhagic diathesis. Common clinicopathologic features included coagulopathic and electrolyte disturbances, hypoproteinemia, increased serum liver enzyme activities, hyperbilirubinemia, and hypocholesterolemia. Cytologic hepatocellular lipid vacuolation was confirmed in 11 dogs examined. In comparisons of clinicopathologic test results between survivor and nonsurvivor dogs, only granular cylindruria (7/21 dogs) consistently predicted death. Best early markers of aflatoxicosis were low plasma activities of anticoagulant proteins (protein C, antithrombin) and hypocholesterolemia. Despite aggressive treatment, many but not all severely affected dogs died.
Conclusions and Clinical Relevance—Serum liver enzyme activities and bilirubin concentration were unreliable early markers of aflatoxin hepatotoxicosis in dogs. Hypocholesterolemia and decreased plasma protein C and antithrombin activities may function as exposure biomarkers.
To characterize clinical, clinicopathologic, and hepatic histopathologic features and outcome for dogs with probable ketoconazole-induced liver injury.
15 dogs with suspected ketoconazole-induced liver injury that underwent liver biopsy.
Medical record data were summarized regarding signalment, clinical signs, clinicopathologic and hepatic histopathologic findings, concurrent medications, ketoconazole dose, treatment duration, and outcome.
Median age and body weight were 8.2 years (range, 5 to 15 years) and 13.0 kg (28.6 lb; range, 8.2 to 38.0 kg [18.0 to 83.6 lb]), respectively. The most common breed was Cocker Spaniel (n = 5). All dogs received ketoconazole to treat cutaneous Malassezia infections. Median daily ketoconazole dose was 7.8 mg/kg (3.5 mg/lb; range, 4.4 to 26.0 mg/kg [2.0 to 11.8 mg/lb]), PO. Treatment duration ranged from 0.3 to 100 cumulative weeks (intermittent cyclic administration in some dogs); 6 dogs were treated for ≤ 10 days. Common clinical signs included lethargy, anorexia, and vomiting. All dogs developed high serum liver enzyme activities. Hepatic histopathologic findings included variable lobular injury, mixed inflammatory infiltrates, and conspicuous aggregates of ceroid-lipofuscin–engorged macrophages that marked regions of parenchymal damage. Five dogs developed chronic hepatitis, including 3 with pyogranulomatous inflammation. Of the 10 dogs reported to have died at last follow-up, survival time after illness onset ranged from 0.5 to 165 weeks, with 7 dogs dying of liver-related causes.
CONCLUSIONS AND CLINICAL RELEVANCE
Findings for dogs with hepatotoxicosis circumstantially associated with ketoconazole treatment suggested proactive monitoring of serum liver enzyme activities is advisable before and sequentially after initiation of such treatment.