The diagnostic approach to asymptomatic dogs with elevated liver enzyme activities - Veterinary Medicine
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The diagnostic approach to asymptomatic dogs with elevated liver enzyme activities
What's the next step when you see an apparently healthy dog that has abnormal liver enzyme results? These clinicians help you figure out when further diagnostic testing is warranted, which tests are indicated, and what conditions to suspect.


Dogs with adrenal hyperplasia syndromes secondary to excess sex hormone production exhibit similar liver enzyme activity elevations as dogs with hyperadrenocorticism do but are frequently asymptomatic (lacking the typical signs of hyperadrenocorticism). Consider testing for hyperadrenocorticism (endogenous ACTH concentration, low-dose dexamethasone suppression test) in dogs with suggestive signs. If the test results for hyperadrenocorticism are negative, consider testing for atypical hyperadrenocorticism (sex hormone panel before and after ACTH stimulation).


Hypothyroidism may result in mild increases in ALP and ALT activities, but these occur less commonly than other clinicopathologic changes including a mild nonregenerative anemia, fasting hypercholesterolemia, and hypertriglyceridemia. Consider testing for hypothyroidism (free T4 concentration, thyroid-stimulating hormone test) in dogs that are of breeds prone to this condition and that exhibit concurrent weight gain, decreased exercise tolerance, or skin and coat changes.

Gastrointestinal disorders

Gastrointestinal disorders such as inflammatory bowel disease and pancreatitis may cause mild to moderate elevations in ALP and ALT activities.16,17 These conditions may give rise to what has been called a reactive hepatopathy. The histologic features include mild to moderate mononuclear periportal inflammatory infiltrates, lipidosis, and focal hepatocellular necrosis.17 These changes are likely secondary to inappropriate gastrointestinal absorption of toxic bacterial products such as endotoxin. Additional clinicopathologic changes that might be seen with inflammatory bowel disease include a peripheral eosinophilia and mild hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia.17 With chronic pancreatitis, hyperlipidemia, hypertriglyceridemia, or mild hyperglycemia may be noted.16 Further work-up should include an abdominal ultrasonographic examination followed by endoscopy with intestinal biopsy or evaluation of serum canine pancreatic lipase immunoreactivity in suspected cases of inflammatory bowel disease and pancreatitis, respectively.

Hepatobiliary causes

Hepatobiliary system disorders to consider include nodular hyperplasia, hepatic tumors, vascular anomalies, and gallbladder mucoceles.

Nodular hyperplasia

Nodular hyperplasia is a common cause of mild to moderate increases in total serum ALP activity in asymptomatic dogs older than 8 years of age. In patients with nodular hyperplasia, other serum liver enzymes activities (transaminases) may be elevated, but hepatic function test results are usually normal.

Grossly, nodular hyperplasia can resemble macronodular cirrhosis or neoplasia. On histologic examination, variable degrees of vacuolar change are seen within hepatocytes, and lipogranulomas are common.13 In more advanced cases, there may be varying degrees of mixed inflammatory cells. In biopsy samples with adequate amounts of tissue, the pathologist should be able to identify normal hepatic tissue surrounding the nodule. Examination of a small needle biopsy sample may yield an inappropriate diagnosis of a vacuolar hepatopathy or chronic inflammatory disease.13

Hepatic tumors

Any primary or metastatic tumor of the liver may result in elevations in ALP, ALT, or AST activities. The most common primary liver neoplasms are hepatocellular adenomas, hepatocellular carcinomas, and bile duct carcinomas.18 The most commonly reported metastatic liver neoplasms are those arising from the mammary glands, spleen, adrenal glands, pancreas, gastrointestinal tract, bone, and lungs.18 The liver can also be involved in other malignant processes including malignant histiocytosis, lymphoma, and systemic mastocytosis. Hepatic wedge, needle, or fine-needle aspiration biopsies are necessary to confirm the diagnosis.

Vascular anomalies

Vascular anomalies within the portal venous system include microscopic (microvascular dysplasia) and macroscopic (congenital extrahepatic or intrahepatic portosystemic shunts) defects in vascular development. Clinical signs are directly related to the degree of diversion of portal blood flow around the liver, so patients with vascular anomalies may be asymptomatic in cases of mild shunting.19 Similar breed predisposition is noted in cases of portosystemic shunts and microvascular dysplasia, and both conditions may be present simultaneously. Typically, portosystemic shunts will be identified in young dogs (less than 2 years of age) while dogs with microvascular dysplasia may not be identified until they are somewhat older.20 In the absence of a concurrent portosystemic shunt, animals with microvascular dysplasia may remain asymptomatic for life; however, others may progress to develop signs of hepatic insufficiency.


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