Alkaline phosphatase is a member of a family of zinc metalloenzymes that are highly concentrated in the microvilli of the bile canaliculus and many other tissues (e.g. bone, intestine, and placenta).
There are four isoenzymes: placental ALP or hPLALP (human placental ALP), germ cell ALP (GCALP or PLALP-like), intestinal ALP (IALP), and tissue-nonspecific ALP (TNALP).
Glycoprotein gamma-glutamyltransferase (GGT) is found on the membranes of cells with high secretory or absorptive activities.
It is also released from the granulation tissue, therefore it can also be elevated during reparative processes not only in the liver, but after a heart attack, wounds, etc.
Its primary function is to catalyze the transfer of a gamma-glutamyl group from peptides to other amino acids.
Besides the liver, it is abundant in many other sources in the body (renal tubules, pancreas, intestine, prostate, testicles, spleen, heart, and brain) but is more specific for biliary disease than alkaline phosphatase because it is not present in bone.
Serum GGT shows identical electrophoretic mobility and lectin affinity reaction to the liver enzyme but different from kidney, urine and pancreas GGT which is increased only 3-fold, thus GGT is slightly more sensitive than ALP in this regard.
The activity level of the GGT in children can be a reliable indicator of bile duct damage.
It is a useful marker to separate the two forms of idiopathic cholestasis, with or without bile duct involvement.
In babies diagnosed with biliary atresia and managed surgically, GGT levels remain high in the blood if the baby is breastfed. This is due to the high level of GGT in human breast milk for at least four weeks after delivery.
There is a relationship between plasma GGT activity and weight, with values 50% higher in individuals with a BMI >30. This is thought to be due to the deposition of fat in the liver (steatosis) in obese people.
Steatosis with an increase in plasma GGT also occurs in diabetes mellitus, nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.
Any liver disease that causes fibrosis and/or cirrhosis, such as alcoholic cirrhosis, primary biliary cirrhosis, secondary biliary cirrhosis, hemochromatosis, α1-antitrypsin deficiency, and Wilson’s disease, will cause an increase in plasma GGT.
Space-occupying lesions, including malignancies (HCC or metastases secondary to malignancy elsewhere in the body) and granulomatous disease, such as sarcoidosis and tuberculosis, are also associated with increased plasma GGT.
Its increase indicates cholestasis and liver damage from toxic substances.One condition that can lead to a significant increase in plasma ALP is benign transient hyperphosphatasemia.
While taking contraceptives and during pregnancy, GGT rises less as it is inhibited by estrogen.
Hyperbilirubinemia also depresses from GGT.
GGT is considered a very sensitive but not very specific index.
Males < 50 U /L
Females < 33 U/L
(Attention, the reference ranges may differ from one laboratory to another, therefore refer to those present on the report).
Increase in GGT values
Alcoholic liver disease
Drug-induced liver disease
Alcohol and drug intoxication (barbiturates, antiepileptics, carbamazepine, cimetidine, methotrexate)
Acute and chronic liver diseases
Pancreatic disease (chronic pancreatitis, pancreatic cancer)
Nephropathies of various kinds
Chronic obstructive pulmonary disease
Liver cancer (both primary and secondary)
Benign transient hyperphosphatasemia
Reduction of GGT values
In early stage of pregnancy