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30 LIVER ENZYME INTERPRETATION PEER REVIEWED HEPATIC ENZYMOLOGY Serum liver enzymes are sensitive but not necessarily specific markers of primary hepatobiliary disease. They are not direct markers of liver function. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular damage, whereas alkaline phosphatase (ALP) and gamma- glutamyltransferase (GGT) are markers of cholestasis. 3 Each individual enzyme can provide information on whether liver disease is present and may provide clues as to the most likely differential diagnosis. Alanine Aminotransferase ALT is a cytoplasmic enzyme found mainly in hepatocytes. However, it is also found in other cells, such as skeletal muscle, renal, and red blood cells, in smaller amounts. ALT is released into the circulation when there is hepatocyte necrosis or increased cell membrane permeability and therefore is a sensitive marker of hepatocellular injury. ALT is the most liver specific of the liver enzymes, but occasionally severe muscle damage or ex vivo hemolysis may increase ALT activity. 4 Concurrent evaluation of creatine kinase activity may help discriminate between muscle disease and liver disease because creatine kinase activity is expected to increase with muscle damage. ALT activity can also be increased in patients with extrahepatic diseases that secondarily affect the liver (eg, feline hyperthyroidism). The reported half-life of ALT has been reported to be about 60 hours in dogs and 3.5 hours in cats. 3 These relatively short half-lives are useful when monitoring recovery after acute liver injury. Conditions that can cause an increase in ALT activity include those listed in Table 1 . Aspartate Aminotransferase AST is a cytoplasmic and mitochondrial enzyme found in hepatocytes and other cells. Reversible or irreversible damage to the liver causes release of the cytoplasmic AST; however, only irreversible damage to the cell will cause release of mitochondrial AST. These two sources of AST are not distinguishable by measuring serum AST activity on a routine biochemistry panel. Increases in AST activity generally parallel those of ALT. However, AST is less specific for liver injury than ALT because increases in activity of AST may also be due to cardiac or skeletal muscle injury 4 or ex vivo hemolysis. The half-life of AST is about 22 hours in dogs and 80 minutes in cats. 3 The shorter half-life compared with ALT means that AST activity decreases and returns to normal before that of ALT in patients with acute liver injury. Conditions that can cause an increase in AST activity include those listed in Table 1 . Alkaline Phosphatase ALP is an enzyme found in hepatocytes that line the bile canaliculi. It is released into the circulation during intra- or extrahepatic cholestasis. This enzyme is sensitive for hepatobiliary disease in dogs (80%), but because of the possible contributions of bone and glucocorticoid-induced isoenzymes to serum ALP activity, its specificity is low (51%). 5 In young, growing animals, ALP activity is normally increased because of the bone isoenzyme, with 71% BOX 1 Metabolic Functions of the Liver 1 Protein metabolism • Synthesis of plasma proteins (albumin, globulins, coagulation proteins) • Deamination of amino acids • Conversion of ammonia to urea • Amino acid synthesis • Interconversion of amino acids Lipid metabolism • β-oxidation of fatty acids • Synthesis of cholesterol • Synthesis of lipoproteins • Synthesis of fatty acids from proteins and carbohydrates Carbohydrate metabolism • Storage of glycogen • Conversion of galactose and fructose into glucose • Gluconeogenesis • Synthesis of many compounds from carbohydrates