What does a Gamma-Glutamyl Transferase (GGT) test measure in an adult patient?

What Does a GGT Test Measure?

The GGT (Gamma-Glutamyl Transferase) test measures a liver enzyme located on cell membranes throughout the body—particularly concentrated in hepatocytes—that serves as a sensitive indicator of hepatobiliary disease, alcohol consumption, and cholestatic liver injury. 1, 2

Primary Clinical Functions

GGT testing serves three main diagnostic purposes in clinical practice:

• Confirms hepatobiliary origin of elevated alkaline phosphatase (ALP), distinguishing liver disease from bone or other tissue sources, since GGT is found in liver, kidneys, intestine, prostate, and pancreas, but not in bone 2

• Detects cholestatic liver disorders, where GGT elevations occur earlier and persist longer than ALP elevations in conditions like primary biliary cholangitis, primary sclerosing cholangitis, and bile duct obstruction 2

• Screens for alcohol consumption, with 73% sensitivity for detecting daily ethanol consumption >50g—higher than AST (50%) or ALT (35%)—making it an early marker for alcohol use, though it is present in about 75% of habitual drinkers 2, 3

Biochemical Role and Disease Associations

The enzyme's primary physiological function involves extracellular catabolism of glutathione, the major cellular antioxidant, thereby playing a crucial role in cellular defense against oxidative stress. 4, 5

Beyond liver disease, elevated GGT independently predicts:

• Cardiovascular disease risk, with 18% per quartile increase in cardiovascular events 5, 3
• Metabolic syndrome, diabetes, and insulin resistance 2, 3
• All-cause mortality, with 26% per quartile increased risk 5, 3

Essential Testing Context

GGT should always be ordered as part of a comprehensive liver panel—never in isolation—including bilirubin, albumin, ALT, AST, ALP, and complete blood count. 1, 2 This is critical because:

• Isolated GGT elevation has low specificity and should not be used as the sole marker of liver disease 2
• GGT elevation alone is not an adequate indication for liver biopsy 2
• Both AST and ALT can be normal even in cirrhosis, so GGT provides complementary information 2

Common Clinical Scenarios

When GGT is elevated, consider these primary causes in order of frequency:

1. Alcohol consumption (most common, ~75% of habitual drinkers) with daily intake >60g causing elevation 2
2. Medications including interferon, antipsychotics, beta-blockers (atenolol), bile acid resins, estrogens, protease inhibitors, steroids, tamoxifen, and thiazides 2
3. Cholestatic liver diseases and bile duct obstruction 2
4. Metabolic conditions including diabetes, obesity, and NAFLD 2
5. Chronic liver diseases including viral hepatitis and cirrhosis 2

Critical Interpretation Pitfalls

Do not assume elevated GGT in cirrhotic patients indicates recent alcohol use—GGT loses specificity in advanced liver disease and elevates regardless of etiology once extensive fibrosis develops. 2 In these cases, direct alcohol markers (urinary ethyl glucuronide, phosphatidylethanol) have 89% sensitivity and 99% specificity, vastly outperforming GGT. 2

Calculate the AST:ALT ratio when interpreting GGT results—a ratio >1 (or >2-3 in some contexts) suggests alcoholic hepatitis or advanced fibrosis/cirrhosis, even if absolute values are within normal ranges. 2

Combining GGT with MCV elevation increases sensitivity for detecting alcohol consumption, as both markers together provide better diagnostic accuracy than either alone. 2, 6