Alanine aminotransferase (ALT)

ALT is a useful indicator of hepatocellular injury in the dog and cat, but not in horses and cattle because they have very little ALT within their hepatocytes. This enzyme is also released with severe muscle injury, therefore, elevations in serum activity should be evaluated in conjunction with other markers of hepatic and muscle damage in dogs and cats. Release of ALT from hepatocytes occurs with rupture or necrosis of the cell, representing irreversible damage, or by blebbing of enzyme packets from the injured cell surface, which could occur with reversible or irreversible injury. The degree of elevation of serum ALT activity does not help distinguish reversible from irreversible damage and, therefore, does not correlate with histopathologic findings.

A single insult to the liver will increase serum ALT activity within a few hours, with peak activity by 24-48 hours. The reported serum half-life ranges from 3 to 60 hours in the dog and 3-4 hours in cats. The increase in ALT activity seen in dogs with hyperadrenocorticism or given exogenous corticosteroids is likely due to glucocorticoid-induced hepatopathy rather than true enzyme induction. Dogs receiving anticonvulsant therapy may have elevated ALT activity also believed to be due to hepatopathy rather than enzyme induction. Dogs and cats with severe hepatobiliary disease resulting in liver failure may have no or mild increases in serum activity of ALT because little ALT remains to be released into the blood. Similarly, hepatic atrophy due to portosystemic shunting of blood or end stage cirrhosis may not be associated with significant ALT release. Serum ALT activity in horses and cattle is probably derived from muscle tissue, and is not used to evaluate hepatic injury, nor is it included in most large animal biochemical panels.

Aspartate aminotransferase (AST)

AST is present in the cytoplasm and mitochondrial membranes of hepatocytes, and skeletal and cardiac muscle. Therefore, increased AST activity can occur with both hepatocellular leakage and muscle injury, and interpretation should be made in conjunction with other indicators of hepatobiliary and muscle disease. Peak activity of AST occurs about 24-36 hours following a single hepatocyte injury; plasma half-life varies with species and ranges from about 1-2 hours in the cat to 50 hours in the horse. AST is often used as an indicator of hepatic injury in large animals but must be interpreted in relation to a muscle-specific enzyme such as creatine kinase (CK).

Sorbitol dehydrogenase (SDH)

SDH is present in the cytoplasm of hepatocytes, with low concentrations in other tissues. Following a single insult to the liver, SDH activity increases within hours and returns to the baseline by about 4-5 days. In horses and ruminants, measurement of SDH activity is particularly useful, given the relative lack of liver specific indicators of hepatocellular damage.

Glutamate dehydrogenase (GLDH)

GLDH is a mitochondrial enzyme and marked increases in activity may be more indicative of hepatic necrosis (i.e. irreversible damage) than the cytosolic leakage enzymes. Serum GLDH is liver specific in the common domestic species and the enzyme is more stable than SDH. Many laboratories are now offering GLDH, particularly for the species in which ALT is not useful, such as horses and ruminants.