What do the parameters of a liver function test, such as Bilirubin, Albumin, Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), and Gamma-Glutamyl Transferase (GGT), indicate?

Understanding Liver Function Test Parameters

Liver function tests (LFTs) measure both hepatocellular injury markers and true synthetic function, with each parameter providing distinct diagnostic information about liver health and disease patterns. 1

Core Parameters and Their Meanings

Aminotransferases (Hepatocellular Injury Markers)

Alanine Transaminase (ALT)

• Most specific marker for hepatocellular injury because it is concentrated primarily in the liver, unlike AST which exists in heart, skeletal muscle, kidneys, and brain 1, 2
• Normal values: 29-33 IU/L in men, 19-25 IU/L in women 1
• Elevations indicate hepatocyte damage and necrosis from causes including fatty infiltration, acute hepatitis, toxic injury, or ischemia 1
• Critical limitation: Normal ALT can occur even with cirrhosis, making it unreliable for excluding advanced disease 2

Aspartate Transaminase (AST)

• Less specific than ALT due to presence in multiple organs 1
• The AST:ALT ratio provides critical diagnostic information 2:
  • Ratio >1 indicates advanced fibrosis or cirrhosis 1, 2
  • In alcohol-related liver disease, AST is typically elevated with AST:ALT ratio >1, though this is neither highly sensitive nor specific 1
  • The ratio remains useful even when both values are within normal range for assessing fibrosis risk 2

Severity Classification for Aminotransferases 1, 2:

• Mild: <5 times upper reference limit
• Moderate: 5-10 times upper reference limit
• Severe: >10 times upper reference limit

Cholestatic Markers

Alkaline Phosphatase (ALP)

• Indicates cholestatic liver disease and estimates impedance of bile flow 1, 2
• Elevated ALP with or without elevated bilirubin suggests cholestasis from biliary obstruction or impaired bilirubin uptake 1
• If ALP is elevated in isolation without other liver enzyme abnormalities, cholestatic disease is suspected 1
• Not liver-specific; can be elevated from bone disease, requiring correlation with GGT 1

Gamma-Glutamyl Transferase (GGT)

• Increases sensitivity for detecting liver disease and is associated with increased liver-related and all-cause mortality 2
• Most sensitive marker with fewest false negatives in diagnosing liver disease 3
• In alcohol-related liver disease, GGT is typically higher than in other liver diseases, though specificity decreases with advanced fibrosis 1
• Helps confirm hepatic origin when ALP is elevated 1, 2
• Reflects both oxidative stress and cholestasis depending on disease context 4:
  • In primary biliary cholangitis and drug-induced liver injury: correlates with cholestasis (ALP, cholesterol) 4
  • In alcoholic liver disease: correlates with both oxidative stress and cholestasis markers 4
  • In non-alcoholic fatty liver disease: correlates with oxidative stress markers (ALT, AST, triglycerides) 4

True Liver Function Markers

Bilirubin

• Evaluates hepatic excretory function and detects cholestasis 2
• Total bilirubin reflects overall bilirubin metabolism 1
• Direct/conjugated bilirubin aids in interpreting elevated ALP and distinguishing cholestatic patterns 2
• Elevations can result from prehepatic, intrahepatic, or posthepatic causes 1

Albumin

• Reflects hepatic protein synthesis capacity and represents true liver function 1, 2
• Decreased levels indicate impaired synthetic function in chronic liver disease 1
• Component of Child-Pugh score for assessing hepatic reserve 1

Prothrombin Time (PT)/International Normalized Ratio (INR)

• Actual marker of hepatocellular synthetic function 1
• Measures production of clotting factors by the liver 1
• Prolonged PT/elevated INR indicates impaired synthetic capacity 1
• Used in both Child-Pugh and MELD scoring systems for liver disease severity 1

Recommended Initial Testing Panel

The optimal initial panel should include 1, 2:

• Bilirubin (total)
• Albumin
• ALT
• ALP
• GGT
• Full blood count (if not performed within previous 12 months)

AST should be added reflexively when ALT or GGT is abnormal to calculate the diagnostically important AST:ALT ratio 2

Critical Interpretation Principles

Context-Dependent Interpretation

• Abnormal results should only be interpreted after reviewing previous results, past medical history, and current medical condition 1
• The extent of abnormality is not necessarily a guide to clinical significance—this is determined by which specific analyte is abnormal and the clinical context 1
• Age and sex-normative values should be used rather than generic upper limits of normal 2

Common Pitfalls to Avoid

• Transient elevations during systemic inflammation or antibiotic treatment should not be confused with true liver disease; persistent abnormalities (>3-6 months) are more significant 2
• Normal aminotransferases do not exclude advanced liver disease including cirrhosis 2
• In advanced cirrhosis, GGT loses specificity because it elevates in extensive fibrosis regardless of cause 1
• AST elevations in alcohol-related liver disease rarely exceed 300 U/mL, with ALT commonly lower 1

When to Investigate Further

• Patients with abnormal liver blood tests should be considered for investigation with a liver aetiology screen irrespective of level and duration of abnormality 1
• In suspected advanced fibrosis or cirrhosis, additional testing should include platelet count and white blood cell count to evaluate for portal hypertension 1