GGT (gamma-glutamyl transferase)

Gamma-glutamyl transferase (GGT, also written GGTP or gamma-GT) is an enzyme found in the membrane of liver cells and of the bile ducts. It is measured in a blood test and rises mainly when there is cholestasis, meaning trouble with the flow of bile. If you were told you have a high GGT, the most important point is that, on its own, it almost never signals a serious disease; instead, it tells the physician where the problem is coming from.

Its greatest value is not diagnosing a specific disease, but confirming that an abnormality in another test originates in the liver. In practice it is always interpreted together with alkaline phosphatase, bilirubin and the liver enzymes, never in isolation.

What is GGT and what does it do?

GGT takes part in the transport of amino acids and in recycling glutathione, a molecule that protects cells from oxidative damage. It is present in many tissues, but is most abundant in the liver, the bile ducts, the kidney and the pancreas. When bile flow is disrupted or the liver receives certain stimuli, this enzyme rises in the blood.

The approximate normal range runs from 0 to 40-50 U/L, with somewhat higher values in men than in women. Levels are similar in children and adults, and do not change meaningfully during pregnancy, which makes GGT useful precisely at that stage.

Why does GGT rise?

GGT is very sensitive but not very specific: it changes easily, though often without meaning liver disease. The most common causes are:

• Cholestasis. Any obstacle to bile flow, inside or outside the liver, raises it. Examples include bile duct stones, tumors and conditions such as primary biliary cholangitis.
• Alcohol. This is one of the best-known triggers. Regular drinking raises GGT, which is why it has been used as a marker of intake, although it is not entirely reliable.
• Medications. Several drugs induce the enzyme, among them some anticonvulsants (such as phenytoin or carbamazepine) and barbiturates. In these cases the rise does not reflect liver damage.
• Fatty liver and metabolic syndrome. GGT often rises in people with excess weight, diabetes or insulin resistance.

Other causes include heart, pancreas and lung disease, so a high GGT does not by itself point to any single organ.

GGT and alkaline phosphatase: telling liver from bone

This is its most valuable role. Alkaline phosphatase can rise from both liver disease and bone disease (and also during pregnancy or growth in children). The trouble is that the test alone does not say where it comes from.

GGT settles that question: it rises with liver and bile duct causes, but not with bone causes. So if alkaline phosphatase is high and GGT is high as well, the origin is most likely the liver or the bile ducts. If alkaline phosphatase is high and GGT is normal, the origin points instead to bone. It is a simple, inexpensive way to steer the workup before ordering more complex tests.

Is a high GGT serious?

Almost never on its own. An isolated GGT elevation, with normal alkaline phosphatase, bilirubin and liver enzymes, is a very common finding and rarely reflects an important liver disease. In that situation extensive testing or repeated ultrasounds up front are not warranted.

The sensible approach is to review the avoidable causes: alcohol intake, medications and fatty liver linked to excess weight. Often, cutting back on alcohol or losing weight brings GGT down on its own over a few weeks or months. A deeper workup is worthwhile when GGT comes with other abnormal liver tests, with symptoms such as jaundice, dark urine or itching, or when the elevation is very marked and persistent.

See also

• Alkaline phosphatase
• Liver enzymes (ALT and AST)
• Bilirubin
• Fatty liver disease