What is the difference between GGT (Gamma-Glutamyl Transferase) and Alk Phos (Alkaline Phosphatase) in evaluating liver versus bone disease?

GGT versus Alkaline Phosphatase in Evaluating Liver versus Bone Disease

GGT is specifically useful for distinguishing between liver and bone sources of alkaline phosphatase (ALP) elevation, as GGT is elevated in liver disease but not in bone disorders. 1

Key Differences Between GGT and ALP

Alkaline Phosphatase (ALP)

• Found in multiple tissues including liver, bone, intestine, and placenta
• Normal range typically 20-200 nmol/L (5-50 mg/L), varies by laboratory, age, and sex 1
• Elevations can occur in both liver and bone disorders
• Cannot independently distinguish between liver and bone sources

Gamma-Glutamyl Transferase (GGT)

• Primarily found in liver and biliary tract
• More specific for liver disease than ALP
• Not elevated in isolated bone disorders
• Serves as a biomarker for alcohol consumption and liver dysfunction 2

Clinical Utility in Differential Diagnosis

When ALP is Elevated

1. Check GGT levels to differentiate between liver and bone sources 1

   • Elevated GGT + Elevated ALP = Likely liver/biliary origin
   • Normal GGT + Elevated ALP = Likely bone origin

2. Diagnostic accuracy:

   • GGT has approximately 85% specificity but only 46.6% sensitivity for hepatic ALP elevation 3
   • GGT within normal limits has about 60% sensitivity for non-hepatic (e.g., bone) ALP elevation 3

Specific Disease Patterns

Liver Disease Patterns

• In alcoholic liver disease:
  • GGT is typically more elevated than in other liver diseases 2
  • AST/ALT ratio >2 in 70% of patients (>3 highly suggestive of alcoholic liver disease) 2
  • GGT loses specificity in advanced liver disease due to elevation with extensive fibrosis 2

Bone Disease Patterns

• In bone disorders:
  • ALP is elevated
  • GGT remains normal
  • Bone-specific ALP isoenzyme testing can confirm bone origin 1

Clinical Approach to Elevated ALP

1. First step: Measure GGT when ALP is elevated 1
2. If GGT is normal: Consider bone disorders such as:
   • Paget's disease
   • Vitamin D deficiency
   • Bone malignancy
   • Hyperparathyroidism
3. If GGT is elevated: Consider liver/biliary disorders such as:
   • Cholestasis
   • Alcoholic liver disease
   • Drug-induced liver injury
   • Viral hepatitis
   • Primary biliary cholangitis or primary sclerosing cholangitis

Important Considerations

• GGT elevation is independently associated with cardiovascular risk and mortality 1
• Redundant GGT testing alongside ALP is common but often unnecessary in primary care 4
• In patients with both liver and bone disease, GGT may be less helpful as both conditions can coexist 3
• The combination of GGT determination with ALP electrophoretic separation provides the most accurate identification of elevated ALP origin 5

Pitfalls to Avoid

• Don't rely solely on GGT: While useful, GGT has limited sensitivity (46.6%) for hepatic ALP elevation 3
• Consider mixed disorders: In 70% of cases with hepatic ALP elevation, a concurrent non-hepatic source may also be present 3
• Avoid over-testing: Routine GGT testing alongside ALP is often redundant and contributes to unnecessary healthcare costs 4
• Remember confounding factors: GGT can be elevated by alcohol consumption, certain medications, and non-alcoholic fatty liver disease, independent of the cause of ALP elevation 2, 6