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Aspartate aminotransferase (AST) is an enzyme involved in the transfer of an amino group from aspartate to alpha ketoglutarate to produce oxaloacetic acid and glutamate. AST is present in most organs. The highest concentrations, listed in descending order, are found in liver, heart, skeletal muscle, kidney, brain, pancreas, lung, leukocytes, and erythrocytes. Because of its wide tissue distribution, elevated AST levels have low specificity for any single disease. AST activities in liver are 7000 times higher than serum activities. Historically, AST has been used clinically to diagnose hepatitis, myocardial infarction, and skeletal muscle disease. AST increase in the absence of ALT increase indicates cardiac or skeletal muscle disease. ALT is a better indicator of liver disease, because of its more limited tissue distribution. AST tends to run slightly higher in males than females due to differences in body mass and varies with age. AST is slightly higher than ALT until the age of 15 to 20 years. Thereafter, AST activity tends to be lower than ALT. At age 60, AST and ALT activities become roughly equal. AST levels are about 15% higher in African American than Caucasian men. Obese men may have mildly elevated AST levels. AST levels can fluctuate between 5 and 10% from one day to the next in the same individual. Moderate exercise increases AST levels for as long as 24 hours, usually less than 3 times the upper limit of normal. The half-life of AST in the circulation is 17 +/- 5 hours. The ratio of AST to ALT is sometimes useful to diagnose specific liver diseases. AST is distributed both in cytoplasm and mitochrondria of hepatocytes, while ALT is distributed mainly in the cytoplasm. Normal serum levels of AST are derived from the cytoplasmic fraction. Mild cell injury results in release of cytoplasmic enzyme, while severe injury releases both cytoplasmic and mitochondrial AST. In most types of liver disease, AST activity is lower than ALT; exceptions include alcoholic hepatitis and Reye syndrome. In alcoholic hepatitis, damage is primarily to the mitochondria and more AST is released than ALT. Also, alcoholic liver disease causes pyridoxine deficiency, which depresses ALT activity, because pyridoxine is an important enzyme cofactor. In alcoholic hepatitis, the AST:ALT ratio is greater than 2.0 and the AST increase is seldom more than 300 U/L. In contrast, viral hepatitis primarily damages the cell membrane, releasing more ALT than AST. The AST:ALT ratio is less than 1. The AST: ALT ratio is less useful in distinguishing alcoholic from other causes of hepatocellular injury in patients with cirrhosis, because the ratio is usually >1.
The chronology and extent of AST elevation provides some insight into the etiology of the underlying liver disease. The highest serum levels occur in viral and toxic hepatitis and ischemic necrosis.
Nonalchololic steatosis can increase both AST and ALT. This condition occurs most commonly in middle aged women with obesity and/or diabetes., but is also associated with jejunoileal bypass surgery, total parenteral nutrition, and drugs such as amiodarone. Both hypo and hyperthyroidism can increase AST and ALT, usually less than three times the upper limit of normal. Other causes of elevated ALT include hemochromatosis, Wilson disease, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis and alpha-1 antitrypsin deficiency. In a patient with increased transaminases, decreasing levels usually indicates clinical improvement. However, a rapid decrease in a patient with acute hepatitis may indicate impending hepatic failure. In this situation, the prothrombin time can be followed as a sensitive index of liver synthetic function. A rare cause of increased AST is the complexing of AST with an immunoglobulin, producing a macroenzyme that is not cleared from the circulation. Macro-AST does not indicate underlying liver disease. Many medications can increase AST levels. The most common drugs are: acetaminophen, nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme (ACE) inhibitors, nicotinic acid, isoniazid, sulfonamides, erythromycin, griseofulvin, and fluconazole. Some people have AST levels below the reference range. Alcoholic liver disease is the most common cause of low AST and ALT. Other causes include uremia, malnutrition, and diabetes mellitus. Reference range is 20 - 50 IU/L (Vitros Analyzer). Specimen requirement is one SST tube. |
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