What does the GGT (Gamma-Glutamyl Transferase) test measure?

What Does the GGT Test Measure?

The GGT (gamma-glutamyl transferase) test measures a liver enzyme that serves as a marker for liver damage, cholestatic disease, and alcohol consumption, while also reflecting the body's oxidative stress status and cellular antioxidant defense mechanisms. 1, 2

Primary Clinical Applications

Liver Disease Detection

• GGT is found in the liver, kidneys, intestine, prostate, and pancreas, but not in bone, making it particularly useful for determining whether elevated alkaline phosphatase (ALP) originates from liver versus bone sources 1
• When both GGT and ALP are elevated together, this confirms the ALP elevation originates from the liver and indicates cholestasis 1
• Initial investigation for potential liver disease should include bilirubin, albumin, ALT, ALP, and GGT together with a full blood count 1

Alcohol Consumption Marker

• Alcohol consumption is the most common cause of elevated GGT, occurring in approximately 75% of habitual drinkers 1
• GGT has 73% sensitivity for detecting daily ethanol consumption exceeding 50g, which is higher than AST (50%) or ALT (35%) 1
• Daily alcohol consumption exceeding 60g can lead to elevated GGT 1
• GGT levels recover slowly following abstinence from alcohol 1

Cholestatic Disease Indicator

• GGT increases occur earlier and persist longer than ALP elevations in cholestatic disorders, making it particularly valuable for detecting bile duct problems 1
• Cholestatic liver diseases including primary biliary cholangitis, primary sclerosing cholangitis, and bile duct obstruction cause elevated GGT 1
• In patients with acute calculus cholecystitis, GGT is the most reliable liver function test for detecting common bile duct stones, with sensitivity of 80.6% and specificity of 75.3% using a cutoff of 224 IU/L 1

Physiological Role

Antioxidant Defense System

• The primary physiological role of GGT is the extracellular catabolism of glutathione, the major thiol antioxidant in mammalian cells 2, 3
• GGT plays an important role in cellular defense by breaking down extracellular glutathione and making its component amino acids available to cells for protection against oxidants produced during normal metabolism 2, 3
• Conditions that increase serum GGT lead to increased free radical production and the threat of glutathione depletion 3

Causes of Elevation

Common Medical Conditions

• Viral hepatitis, cirrhosis, and other chronic liver diseases 1
• Diabetes and insulin resistance 1
• Obesity 1
• Nonalcoholic fatty liver disease (NAFLD), where GGT levels typically range from low normal to >400 U/L 1
• Infiltrative liver diseases including sarcoidosis, amyloidosis, and hepatic metastases 1

Medication-Related Causes

• Common medications that elevate GGT include interferon, antipsychotics, beta-blockers (such as atenolol), bile acid resins, estrogens, protease inhibitors, retinoic acid drugs, sirolimus, steroids, tamoxifen, and thiazides 1

Interpretation Considerations

Diagnostic Limitations

• GGT elevation alone has low specificity and should be interpreted in context with other liver enzymes 1
• Isolated GGT elevations can occur in the absence of underlying liver disease, and therefore GGT should not be used as an exclusion criterion or sole marker of liver disease 1
• An isolated increase in GGT is not associated with major liver pathology and is not an adequate indication on its own for liver biopsy 1

Enhanced Diagnostic Accuracy

• The AST/ALT ratio exceeding 2 (or 3) suggests alcoholic hepatitis 1
• GGT elevation combined with MCV (mean corpuscular volume) elevation increases sensitivity for detecting alcohol consumption 1, 4
• In alcohol-associated liver disease, GGT is inadequate on its own to establish alcohol use and should be combined with other biomarkers, physical exam, and clinical interview 1

Prognostic Significance

Disease Risk Prediction

• Even mildly elevated GGT independently predicts increased risk for cardiovascular disease, diabetes, metabolic syndrome, and all-cause mortality 1, 5
• High GGT levels in patients with chronic hepatitis delta independently predict clinical outcomes 1
• People with high serum GGT have higher mortality, partly because of the association between GGT and other risk factors and partly because GGT is an independent predictor of risk 3

Advanced Liver Disease

• GGT levels are rarely low in advanced fibrosis or cirrhosis, where values are typically much higher 1
• GGT loses specificity in advanced liver disease because it elevates regardless of etiology once extensive fibrosis develops 1

Common Pitfalls

• Do not rely on GGT as a single marker—it must be interpreted alongside AST, ALT, ALP, and bilirubin for accurate diagnosis 1
• Avoid over-interpreting isolated GGT elevation as definitive evidence of liver disease without corroborating findings 1
• Remember that 15-50% of patients with acute cholecystitis show liver function test elevation without common bile duct stones due to acute inflammation rather than direct biliary obstruction 1
• GGT may be elevated due to non-alcoholic causes including obesity, diabetes, smoking, or medication use 4