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Gamma Glutamyl Transferase (GGT)


Definition


  • The activity of this membrane-bound enzyme comes primarily from the liver. GGT is responsible for the extracellular metabolism of glutathione, the main antioxidant in cells. It is slightly more sensitive than ALP in obstructive liver disease.
  • Normal range:
    • 0 " “3 months: 4 " “120 IU/L
    • 3 months " “1 year: 2 " “35 IU/L
    • 1 " “16 years: 2 " “25 IU/L
    • ≥16 years: 7 " “50 IU/L

Use


  • To diagnose and monitor hepatobiliary disease; most sensitive enzymatic indicator of liver disease
  • To ascertain whether observed elevations of ALP are due to skeletal disease (normal GGT) or reflect the presence of hepatobiliary disease (elevated GGT)
  • As a screening test for occult alcoholism
  • To aid in diagnosis of liver disease in the presence of bone disease, pregnancy, or childhood, which increase serum ALP and LAP but not GGT

Interpretation


Increased In


  • DM, hyperthyroidism, RA, COPD.
  • Drugs (phenytoin, carbamazepine, cimetidine, furosemide, heparin, methotrexate, oral contraceptives, and valproic acid).
  • Liver disease " ”generally parallels changes in serum ALP, LAP, and 5 " ²-NT but is more sensitive.
  • Acute hepatitis. Elevation is less marked than that of other liver enzymes, but it is the last to return to normal and, therefore, is useful to indicate recovery.
  • Chronic active hepatitis; increased (average more than seven times ULN) more than in acute hepatitis; more elevated than AST and ALT. In dormant stage, it may be the only enzyme elevated.
  • Alcoholic hepatitis; average increase >3.5 times ULN.
  • Alcohol abuse; a GGT/ALP ratio >2.5 is highly suggestive.
  • Cirrhosis. In inactive cases, average values are lower (four times ULN) than in chronic hepatitis. Increases of more than 10 " “20 times normal in cirrhotic patients suggest superimposed primary carcinoma of the liver (average increase >21 times ULN).
  • Primary biliary cirrhosis. Elevation is marked: average >13 times ULN.
  • Fatty liver; elevation parallels that of AST and ALT but is greater.
  • Obstructive jaundice. Increase is faster and greater than that of serum ALP and LAP; average increase more than five times ULN.
  • Liver metastases; parallels ALP; elevation precedes positive liver scans. Average increase >14 times ULN.
  • Cholestasis. In mechanical and viral cholestasis, GGT and LAP are increased about equally, but in drug-induced cholestasis, GGT is much more increased than LAP. Average increase more than six times ULN.
  • Children; much more increased in biliary atresia than in neonatal hepatitis (300 IU/L is useful differentiating level). Children withα1-antitrypsin deficiency have higher levels than other patients with biliary atresia.
  • Pancreatitis. The GGT level is always elevated in acute pancreatitis. In chronic pancreatitis, it is increased when there is involvement of the biliary tract or active inflammation.
  • AMI; increased in 50% of patients. Elevation begins on the 4th to the 5th day, reaching a maximum at 8 " “12 days. With shock or acute right heart failure, an early peak may appear within 48 hours, with a rapid decline followed by a later rise.
  • When increased, it is a risk factor for myocardial infarction and cardiac death.
  • Heavy use of alcohol; the most sensitive indicator and a good screening test for alcoholism, because elevation exceeds that of other commonly assayed liver enzymes.
  • Some cases of carcinoma of the prostate.
  • Neoplasms, even in the absence of liver metastases; especially malignant melanoma, carcinoma of the breast and lung; highest levels seen in hypernephroma.
  • Others (e.g., gross obesity [slight increase], renal disease, cardiac disease, postoperative state).

Decreased In


  • Hypothyroidism

Normal In


  • Pregnancy (in contrast to serum ALP, LAP) and children older than 3 months of age; therefore, may aid in differential diagnosis of hepatobiliary disease occurring during pregnancy and childhood
  • Bone disease or patients with increased bone growth (children and adolescents); therefore, useful in distinguishing bone disease from liver disease as a cause of increased serum ALP
  • Renal failure
  • Strenuous exercise

Limitations


  • Half-life is about 7 " “10 days; in alcohol-associated liver injury, the half-life is increased to as much as 28 days, suggesting impaired clearance.
  • Day-to-day variations are 10 " “15%; approximately double in African Americans.
  • There is a 25 " “50% increase with higher body mass index.
  • Values are 25% lower during early pregnancy.
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