Clinical and Interpretive

Measurement of gamma-glutamyltransferase is useful in diagnosing and monitoring hepatobiliary disease. It is currently the most sensitive enzymatic indicator of liver disease. Measurement of GGT is useful in ascertaining whether observed elevations of alkaline phosphatase are due to skeletal disease (normal gamma-glutamyltransferase: GGT) or reflect the presence of hepatobiliary disease (elevated GGT). GGT can be used as a screening test for occult alcoholism.

Gamma-glutamyltransferase (GGT) is primarily present in kidney, liver, and pancreatic cells. Small amounts are present in other tissues. Even though renal tissue has the highest level of GGT, the enzyme present in the serum appears to originate primarily from the hepatobiliary system, and GGT activity is elevated in any and all forms of liver disease. It is highest in cases of intra- or post-hepatic biliary obstruction, reaching levels some 5 to 30 times normal. It is more sensitive than alkaline phosphatase (ALP), leucine aminopeptidase, aspartate transaminase, and alanine amintotransferase in detecting obstructive jaundice, cholangitis and cholecystitis; its rise occurs earlier than with these other enzymes and persists longer. Only modest elevations (2-5 times normal) occur in infectious hepatitis, and in this condition GGT determinations are less useful diagnostically than are measurements of the transaminases. High elevations of GGT are also observed in patients with either primary or secondary (metastatic) neoplasms. Elevated levels of GGT are noted not only in the sera of patients with alcoholic cirrhosis but also in the majority of sera from persons who are heavy drinkers. Studies have emphasized the value of serum GGT levels in detecting alcohol-induced liver disease. Elevated serum values are also seen in patients receiving drugs such as phenytoin and phenobarbital, and this is thought to reflect induction of new enzyme activity.Normal values are observed in various muscle diseases and in renal failure. Normal values are also seen in cases of skeletal disease, children older than 1 year and in healthy pregnant women-conditions in which ALP is elevated.

An elevation of gamma-glutamyltransferase (GGT) activity is seen in any and all forms of liver disease, although the highest elevations are seen in intra- or post-hepatic biliary obstruction. Elevated values can also indicate alcoholic cirrhosis or individuals who are heavy drinkers. The finding of increased GGT and alkaline phosphatase (ALP) activity is consistent with hepatobiliary disease. The finding of normal GGT activity and increased ALP activity is consistent with skeletal disease.

Gamma-glutamyltransferase activity is inducible by drugs such as phenytoin and phenobarbital, and therefore elevations should not be considered indicative of liver disease until drug use is ruled out. Elevations are also seen after ingestion of alcoholic beverages. In very rare cases, gammopathy, in particular, type IgM (Waldenstroms macroglobinemia) may cause unreliable results.