Gamma-Glutamyl Transferase (GGT): Clinical Significance and Applications
Gamma-Glutamyl Transferase (GGT) is a liver enzyme primarily involved in glutathione metabolism that serves as a sensitive marker for liver injury, alcohol consumption, and oxidative stress, with significant associations to cardiovascular disease risk, metabolic syndrome, and all-cause mortality. 1, 2
Biochemical Role and Function
- GGT is an enzyme located on plasma membranes of most cells and tissues, but predominantly in hepatocytes (liver cells)
- Primary physiological function: Extracellular catabolism of glutathione, the major antioxidant in mammalian cells 2
- Plays crucial roles in:
- Cellular defense against oxidative stress
- Xenobiotic (foreign substance) metabolism
- Glutathione recycling and homeostasis
Clinical Applications
1. Liver Disease Detection
- Sensitive indicator of liver injury and biliary tract involvement 1
- Elevated in approximately 75% of habitual alcohol drinkers, making it useful for monitoring alcohol abstinence 1
- Used to distinguish between liver and bone sources of elevated alkaline phosphatase (ALP) 3
2. Diagnostic Value in Cholestasis
- Helps differentiate types of cholestasis:
- Low-GGT progressive familial intrahepatic cholestasis (PFIC)
- High-GGT progressive familial intrahepatic cholestasis 1
3. Cardiovascular and Metabolic Risk Assessment
- Independent biomarker for metabolic syndrome 4
- Associated with increased risk of:
Reference Ranges and Interpretation
- Normal GGT levels vary by laboratory, age, and sex 3
- Typically higher in:
- Children and adolescents
- Elderly individuals
- Slightly different reference ranges for males and females 3
Factors Affecting GGT Levels
Elevating Factors:
- Alcohol consumption (most common cause) 1
- Liver diseases (hepatitis, fatty liver, cholestasis)
- Medications (anticonvulsants, certain antibiotics)
- Obesity
- Smoking
- Drug use 1
Important Clinical Considerations:
- GGT levels recover slowly following alcohol abstinence 1
- Combining GGT with other tests (AST, ALT, MCV, CDT) improves diagnostic accuracy for alcohol-related liver disease 1
- GGT elevation alone has limited specificity - must be interpreted in clinical context 3
Monitoring Applications
- Useful for monitoring:
- Alcohol abstinence in patients with alcohol use disorder
- Response to treatment in liver diseases
- Recommended monitoring interval: every 3-6 months depending on severity 3
Clinical Pitfalls and Caveats
- GGT is highly sensitive but lacks specificity for particular liver disease etiologies 6
- Can be elevated in non-liver conditions (diabetes, heart disease, kidney disease)
- Population levels of GGT have shown an upward trend over time, particularly in the US and Korea 7
- Complete alcohol cessation is crucial when managing elevated GGT 3
- Don't attribute elevated GGT solely to liver disease without ruling out other causes 3
GGT has evolved from being considered merely a liver function test to an important biomarker with significant implications for cardiovascular, metabolic, and overall mortality risk assessment, making it a valuable component in comprehensive health evaluations.