Measurement of serum ALT and AST levels is a highly sensitive screening test for hepatobiliary disease.
The sensitivity of serum transaminases must be considered in light of the fact that serum ALT and AST activity can be increased under conditions in which the liver is not the primarily diseased organ. One report has noted that the positive predictive value of a twofold increase in serum ALT activity to detect primary liver disease is only 29%.1 The liver receives a rich blood supply from both the arterial and portal venous systems and is a dynamic metabolic organ with various functions, including fat digestion, intermediary metabolism, and detoxification of endogenous and exogenous compounds. Extrahepatic systemic disorders and diseases in organ systems drained by the portal circulation-particularly the gastrointestinal tract and pancreas-can damage the liver and increase levels of serum ALT and AST. Thus, under these conditions, increased liver enzymes may not reflect the presence of clinically important hepatic disease (Table 1). In addition, in dogs corticosteroids and phenobarbital can increase serum transaminase activity, particularly that of ALT, due to enzyme induction.2-6 It should be noted, however, that corticosteroids and phenobarbital can also increase serum ALT and AST activity due to hepatotoxicity.2-6
Serum transaminase levels increase when active disease causes hepatocyte membrane damage. However, since the liver has a huge regenerative capacity and great functional reserve, the magnitude of elevation in serum ALT or AST is not indicative of the extent of functional impairment and thus has limited prognostic value. In fact, ALT or AST elevations may be quite mild in severe end-stage liver disease because of enzyme depletion secondary to replacement of hepatocytes by fibrous tissue. For these reasons, a single serum ALT or AST measurement should never be used to make a definitive diagnosis or to establish a prognosis. The clinical significance of increased serum ALT or AST activity is improved by (1) monitoring for sequential enzyme elevations; (2) assessing for concurrent increases in other serum markers of liver disease (serum alkaline phosphatase, serum gamma-glutamyl transpeptidase, serum bilirubin); (3) measuring liver function (serum total bile acids); and/or (4) obtaining a liver biopsy.
Elevations in serum ALT or AST are commonly noted on serum biochemical profiles in dogs. In a study of 261 dogs presented for various disorders to a referral hospital, 47% had elevations in ALT.7 In another study of 1022 blood samples from both healthy and sick animals submitted to a private veterinary laboratory, elevations in ALT and AST were seen in 20.3% and 12.1%, respectively.8
Increases in ALT or AST may indicate breed-related hepatopathies in Doberman pinschers, cocker spaniels, Labrador retrievers, Bedlington terriers, dalmatians, and Skye terriers. In addition, serum transaminase levels may be mildly elevated in dogs with congenital vascular diseases, such as portosystemic vascular anomalies or primary hypoplasia of the portal vein, disorders with distinct breed predispositions.9
In most situations, ALT is considered a liver-specific enzyme in dogs and cats. In dogs, severe muscle necrosis can increase serum ALT, but a muscle source for the enzyme can be eliminated by simultaneous measurement of serum creatine kinase.10
Elevations in serum ALT are associated with reversible or irreversible damage to the hepatocyte plasma membrane. Increased serum ALT activity has the highest sensitivity (80% to 100%) for inflammation, necrosis, vacuolar hepatopathy, and primary neoplasia. Reduced sensitivity has been noted for the detection of liver failure due to feline hepatic lipidosis (72%), hepatic congestion (70%), metastatic neoplasia, portosystemic vascular anomalies, and secondary hepatic lipidosis (60%).1,11
The magnitude of serum ALT elevation is generally proportional to the number of injured hepatocytes. Since the t1/2 in dogs is about 2.5 days, a 50% decrease over 2 to 3 days is a good prognostic sign. In cats, the serum t1/2 is much shorter (around 6 hrs), so return to normal values after an acute insult occurs faster.
Compared with ALT, AST is more sensitive but less specific for detection of hepatic disease.11 Serum AST is derived from liver, skeletal muscle, and cardiac muscle sources. In humans, there is both a cytosolic and mitochondrial liver isoenzyme, and this is presumably true in dogs and cats. The cytosolic enzyme is released with reversible or irreversible damage to hepatocyte plasma membranes and usually parallels increases in ALT. The mitochondrial enzyme is released only with irreversible hepatocyte injury.
Generally, the degree of serum AST elevation for a given amount of hepatocyte damage is less than the degree of ALT elevation. If serum AST is much higher than serum ALT, a muscle source of the enzymes should be explored. In humans, a disproportionate increase in AST over ALT is also seen in conjunction with severe, irreversible hepatocyte injury, in which large amounts of mitochondrial AST are released into the serum.12
The t1/2 of AST in dogs and cats has been reported as 12 hours and 77 minutes, respectively. Because the t1/2 of serum AST is shorter in dogs than the t1/2 for serum ALT, levels of the former enzyme generally return to normal faster. AST has been reported to be more sensitive than ALT for the detection of metastatic disease in the liver (70% to 95% vs 45%, respectively).13 Hemolysis also increases serum AST.