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.


Serum AST activity increases from leakage secondary to hepatocyte membrane injury, so it typically parallels serum ALT activity increases. Increased serum AST activity, in the absence of increased ALT activity, indicates an extrahepatic source, most likely muscle injury.4 Marked elevations in AST activity are suggestive of irreversible hepatocyte injury with release of mitochondrial AST stores. AST half-life is 22 hours.6

Measuring AST activity is somewhat more sensitive but less specific for detecting hepatic disease than is measuring ALT activity.3 Typically, there is little to no induction of serum AST with corticosteroid or phenobarbital treatment.3,5,7

Serum alkaline phosphatase

Alkaline phosphatase is a membrane-bound enzyme present in many tissues. Three major isoenzymes contribute to total serum ALP: bone, liver, and corticosteroid isoenzymes.1,3,8

Bone ALP accounts for about one-third of the total serum ALP and is elevated with conditions associated with increased osteoblastic activity such as bone growth, osteomyelitis, osteosarcoma, and secondary renal hyperparathyroidism.3

Liver ALP is a membrane-bound enzyme present on biliary epithelial cells and hepatocytes. Liver ALP half-life is 70 hours.3,8 The largest increases in liver ALP activities are associated with focal or diffuse cholestatic disorders and primary hepatic neoplasms (hepatocellular and bile duct carcinoma). Less dramatic increases are found in cases of hepatic necrosis, hepatitis, and nodular hyperplasia. Liver ALP can also be induced by corticosteroid or phenobarbital administration.3,5,7,9

Corticosteroid ALP isoenzyme is produced in the liver and is located on the hepatocyte plasma membranes lining the bile canaliculi and sinusoids.3 Corticosteroid ALP has a similar half-life to liver ALP. Corticosteroid ALP contributes to total serum ALP in dogs exposed to exogenous corticosteroids or in cases of spontaneous hyperadrenocorticism.3 However, increased corticosteroid ALP activity has also been associated with chronic illness, possibly secondary to stress and concomitant increases in endogenous glucocorticoid secretion.1,3,8

Increased ALP activity is one of the most common abnormalities detected on serum chemistry profiles in ill dogs. ALP activity measurement has a high sensitivity (80%) for hepatobiliary disease, but its specificity is low (51%). If elevated ALP activity is noted with a concurrent increase in serum GGT activity, specificity for liver disease increases to 94%.8


Serum GGT activity is largely derived from the hepatobiliary system. In dogs, hepatic GGT is located on the hepatocyte canalicular membrane. GGT activity appears to have a lower sensitivity but higher specificity (87%) for detecting hepatobiliary disease than ALP activity does.8

The most marked elevations of GGT activity result from diseases of the biliary epithelium such as bile duct obstruction and cholecystitis.3 Moderate elevations can also be found with primary hepatic neoplasia (hepatocellular and biliary carcinoma) and corticosteroid induction.1,3,7,8 Mild elevations are found in cases of hepatic necrosis and anticonvulsant administration.3,5,9


Table 1: Disorders Associated with Elevated Serum Hepatobiliary Enzyme Activity in Asymptomatic Dogs
Asymptomatic dogs with increases in serum hepatobiliary enzyme activities may have either extrahepatic disease or primary hepatobiliary disease (Table 1). The first steps in evaluating these dogs are to get a thorough history and perform a physical examination. In addition, a minimum database (including a complete blood count, full serum chemistry profile, and urinalysis) should be obtained in all cases.


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