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Aminotransferases (AST, ALT)


Definition


  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) are members of the transaminase family of enzymes, widely distributed in cells throughout the body. AST is primarily found in the heart, liver, skeletal muscle, and kidney, whereas ALT is found primarily in the liver and kidney, with lesser amounts in the heart and skeletal muscle. AST and ALT activities in the liver are about 7,000 and 3,000 times serum activities, respectively.
  • Normal range:
    • AST:
      • Less than or equal to 1 year: 30 " “80 U/L
      • Greater than 1 year: 10 " “40 U/L
    • ALT:
      • Less than or equal to 1 year: 5 " “50 U/L
      • Greater than 1 year: 10 " “40 U/L

Use


  • Most sensitive tests for acute hepatocellular injury (e.g., viral, drug); precedes increase in serum bilirubin by approximately 1 week

Interpretation


Increased In


  • Hepatocellular damage, liver cell necrosis, or injury of any cause.
  • Alcoholic hepatitis (AST > ALT).
  • Viral and chronic hepatitis (ALT > AST).
  • Early acute hepatitis: AST is usually higher initially, but by 48 hours, ALT is usually higher.
  • AST levels of 500 U/L suggest acute hepatocellular injury; seldom >500 U/L in obstructive jaundice, cirrhosis, viral hepatitis, AIDS, alcoholic liver disease.
  • Acute fulminant viral hepatitis: Abrupt AST rise may be seen (rarely >4,000 IU/L) and declines more slowly; positive serologic tests and acute chemical injury.
  • Congestive heart failure, arrhythmia, sepsis, and GI hemorrhage AST levels reach to a peak of 1,000 " “9,000 U/L, declining by 50% within 3 days and to <100 U/L within a week, suggesting shock liver with centrolobular necrosis. Serum bilirubin and ALP reflect underlying disease.
  • Trauma to skeletal or heart muscle.
  • Acute heart failure (AST > ALT).
  • Severe exercise, burns, heat stroke.
  • Hypothyroidism.
  • Drug-induced injury to the liver.
  • Acute bile duct obstruction due to a stone: Rapid rise of AST and ALT to very high levels (e.g., >600 U/L and often >2,000 U/L) followed by a sharp fall in 12 " “72 hours is said to be typical.

Decreased In


  • Azotemia
  • Chronic renal dialysis
  • Pyridoxal phosphate deficiency states (e.g., malnutrition, pregnancy, alcoholic liver disease)

Limitations


  • Half-life of AST is 18 hours and that of ALT is 48 hours.
  • The patient is rarely asymptomatic with ALT and AST levels >1,000 U/L.
  • AST >10 times normal indicates acute hepatocellular injury, but lesser increases are nonspecific and may occur with virtually any form of liver injury.
  • Increases ≤8 times upper limit of normal are nonspecific; may be found in any liver disorder.
  • Rarely increased >500 U/L (usually <200 U/L) in posthepatic jaundice, AIDS, cirrhosis, and viral hepatitis.
  • Usually <50 U/L in fatty liver.
  • Less than 100 U/L in alcoholic cirrhosis; ALT is normal in 50%, and AST is normal in 25% of these cases.
  • Less than 150 U/L in alcoholic hepatitis (may be higher if the patient has delirium tremens).
  • Less than 200 U/L in approximately 50% of patients with cirrhosis, metastatic liver disease, lymphoma, and leukemia.
  • Normal values may not rule out liver disease: ALT is normal in 50%, and AST is normal in 25% of cases of alcoholic cirrhosis.
  • Degree of increase has a poor prognostic value.
  • Serial determinations reflect clinical activity of liver disease. Persistent increase may indicate chronic hepatitis.
  • Mild increase of AST and ALT (usually <500 U/L) with ALP increased greater than three times normal indicates cholestatic jaundice, but more marked increase of AST and ALT (especially >1,000 U/L) with ALP increased less than three times normal indicates hepatocellular jaundice.
  • Rapid decline in AST and ALT is a sign of recovery from disease but in acute fulminant hepatitis may represent loss of hepatocytes and poor prognosis.
  • Poor correlation of increased concentration with extent of liver cell necrosis and has a little prognostic value.
  • Although AST, ALT, and bilirubin are most characteristic of acute hepatitis, they are unreliable markers of severity of injury.
  • ALT has 45% variation during the day; highest in afternoon and lowest at night. Both AST and ALT exhibit 10 " “30% variation from 1 day to next. AST levels are 15% higher in African American men.
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