What are the normal lab value ranges for liver function tests, including Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Gamma-Glutamyl Transferase (GGT), total bilirubin, direct bilirubin, and albumin?

Normal Ranges for Liver Function Tests

The normal reference ranges for liver function tests according to the American Association for the Study of Liver Diseases are: ALT 0-40 U/L, AST 0-40 U/L, ALP 40-120 U/L, GGT 0-50 U/L, total bilirubin 0.1-1.2 mg/dL, and albumin 3.5-5.0 g/dL. 1

Detailed Reference Ranges

Aminotransferases

• Alanine Transaminase (ALT)

  • Normal range: 0-40 U/L
  • Upper Limit of Normal (ULN): ~40-45 U/L in most laboratories 1
  • May vary by gender (typically higher in males)

• Aspartate Transaminase (AST)

  • Normal range: 0-40 U/L
  • Typically rises in parallel with ALT but with different ratios depending on etiology
  • AST:ALT ratio >2 suggests alcoholic liver disease
  • AST:ALT ratio <1 suggests metabolic-related fatty liver 1

Cholestatic Enzymes

• Alkaline Phosphatase (ALP)

  • Normal range: 40-120 U/L 1
  • Values typically <2× ULN even in mild liver disease
  • Age-dependent (higher in children/adolescents and elderly)
  • Should be confirmed to be of hepatobiliary origin with GGT and/or ALP isoenzyme fractionation 2

• Gamma-Glutamyl Transferase (GGT)

  • Normal range: 0-50 U/L 1
  • May range from normal to >400 U/L in NAFLD patients
  • More specific for hepatobiliary disease than ALP
  • Often used to confirm hepatic origin of elevated ALP

Bilirubin

• Total Bilirubin

  • Normal range: 0.1-1.2 mg/dL 1
  • Usually normal until advanced stages of liver disease
  • Values >1.0× ULN may be exclusion criteria for clinical trials in certain liver diseases 2

• Direct (Conjugated) Bilirubin

  • Normal range: 0-0.3 mg/dL
  • Elevation suggests impaired biliary excretion

Synthetic Function

• Albumin
  • Normal range: 3.5-5.0 g/dL
  • Decreased levels indicate impaired synthetic function
  • Age-dependent (lower in elderly)

Interpretation of Abnormal Values

Classification of Elevations

Liver enzyme elevations are typically classified as:

• Mild: <5× ULN
• Moderate: 5-10× ULN
• Severe: >10× ULN 1

Important Considerations

• The magnitude of liver enzyme elevation does not necessarily correlate with clinical significance or prognosis 1
• The clinical context and specific analyte that is abnormal are more important than the degree of elevation
• Patients with significant liver fibrosis may have liver enzymes within normal reference ranges 1
• Laboratory-specific reference ranges may vary slightly; absolute values should be reported and analyzed along with multiples of ULN values 2

Special Populations

Gender Differences

• ALT, GGT, and total bilirubin typically have gender-specific reference ranges (generally higher in males) 1
• In adolescents, the upper normal limits for boys vs. girls are:
  • ALT: 32 vs. 20 U/L
  • GGT: 24 vs. 19 U/L
  • AST: 33 vs. 26 U/L
  • ALP: 385 vs. 183 U/L 3

Age Considerations

• ALP and albumin reference ranges vary with age 1
• ALP is higher in children, adolescents, and pregnant women due to bone growth
• Albumin tends to decrease with advanced age

Common Pitfalls in Interpretation

1. Failure to consider non-hepatic sources:

   • ALP may originate from bone, placenta, or intestine
   • AST is present in cardiac and skeletal muscle

2. Not accounting for laboratory variability:

   • Reference ranges can vary between laboratories
   • Some labs report different ULNs for different sex and age groups 2

3. Overlooking mild elevations:

   • Even mild elevations can indicate significant liver disease
   • Normal values don't exclude liver pathology

4. Misinterpreting patterns:

   • Hepatocellular pattern: Predominant elevation of aminotransferases
   • Cholestatic pattern: Predominant elevation of ALP and GGT
   • Mixed pattern: Elevation of both aminotransferases and cholestatic enzymes

Remember that liver function tests should always be interpreted in the context of the patient's clinical presentation, medical history, and other laboratory findings 1. Isolated abnormalities often require repeat testing and further investigation.