Table 1

Categorization of liver diseases by pattern of elevation of liver enzymes

Aminotransferases

The aminotransferases (previously called transaminases) are located in hepatocytes and are sensitive indicators of hepatocyte injury. They are useful in detecting acute hepatocellular diseases, such as hepatitis.2 They consist of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Aminotransferases catalyze the transfer of the α-amino groups from aspartate or alanine to the α-keto group of ketoglutaric acid, forming oxaloacetic acid and pyruvic acid, respectively. The enzymatic reduction of oxaloacetic acid and pyruvic acid to malate and lactate, respectively, is coupled to the oxidation of the reduced form of nicotinamide dinucleotide to nicotinamide dinucleotide. Because only nicotinamide dinucleotide absorbs light at 340 nm, this reaction can be followed spectrophotometrically by the loss of absorptivity at 340 nm, and provides an accurate method to assay aminotransferase activity.3

AST and ALT are present in the serum at low concentrations, usually less than 30 to 40 IU/L.4 The normal range varies among clinical laboratories, based on measurements in specific populations. Several factors have been shown to influence ALT activity, such as gender and obesity.5 Men tend to have a higher serum ALT activity compared with women.

ALT is found in highest concentration in hepatocytes and in very low concentrations in any other tissues. In contrast, AST is found in many other tissues including muscle (cardiac, skeletal, and smooth muscle); kidney; and brain.2 Thus, ALT is a more specific marker for liver injury. A ratio of AST/ALT greater than five, especially if ALT is normal or slightly elevated, is suggestive of injury to extrahepatic tissues, such as skeletal muscle in the case of rhabdomyolysis or strenuous exercise.

AST is present in the cytoplasm and mitochondria, whereas ALT is only present in the cytoplasm (Fig. 1). About 80% of AST activity in the liver is derived from the mitochondrial isoenzyme, whereas most serum AST activity is derived from the cytosolic isoenzyme in healthy persons.2 Processes leading to necrosis of hepatocytes or damage to the hepatocyte cell membrane with increased permeability result in release of AST and ALT into the blood.6

Assessing the pattern and degree of elevation in liver enzymes can help elucidate the cause of liver injury and direct subsequent diagnostic testing and management. Any type of liver cell injury can cause moderate elevations in serum aminotransferase levels. Levels up to 300 IU/L are nonspecific and can be seen in any type of liver disorder.7 Massive elevations with aminotransferase levels greater than 1000 IU/L are almost exclusively seen in disorders associated with extensive hepatocellular injury, most commonly caused by (1) toxin- or drug-induced liver injury, (2) acute ischemic liver injury, or (3) acute viral hepatitis. Severe autoimmune hepatitis or Wilson disease may also cause markedly elevated aminotransferases.

ALT is present in highest concentration in periportal hepatocytes (Zone 1) and in lowest concentration in hepatocytes surrounding the central vein (Zone 3). AST, however, is present in hepatocytes at more constant levels (Fig. 2). Hepatocytes around the central vein have the lowest oxygen concentration and thus are more prone to damage in the setting of acute hepatic ischemia that can occur as the result of acute hypotension or severe cardiac disease. The ensuing centrilobular necrosis results in a rapid rise in aminotransferases, with AST value greater than ALT in the initial days of hepatic injury.

After there is no further injury to hepatocytes, the rate of decline of AST and ALT depends on their rate of clearance from the circulation. AST and ALT are catabolized by the liver, primarily by cells in the reticuloendothethlial system. The plasma half-life of AST and ALT are 17 ± 5 hours and 47 ± 10 hours, respectively.2 Thus, AST declines more rapidly than ALT, and ALT may be...