Liver Function Tests (LFTs)

1. Hepatocellular Enzymes (Liver Cell Damage Markers)

ALT (Alanine Aminotransferase)

• More liver-specific than AST
• Elevated primarily in hepatocellular injury (hepatitis, drug toxicity, ischemia)
• Sensitive marker of acute hepatocyte damage

AST (Aspartate Aminotransferase)

• Less liver-specific - also found in heart, skeletal muscle, kidney, and red blood cells
• Elevated in hepatitis, cirrhosis, cardiac disease, and muscle disorders
• AST:ALT ratio >2 is suggestive of alcoholic liver disease

In acute hepatitis: AST and ALT are markedly elevated (often >10x ULN); total protein, albumin, and ammonia remain normal (since <80% of liver is destroyed)

In fulminant hepatic failure: AST and ALT can exceed 10,000 IU/L, with a disproportionate rise of AST over ALT - a medical emergency requiring transplant evaluation

In cirrhosis: AST and ALT are paradoxically normal or only mildly elevated, because fibrosis replaces hepatocytes with little active inflammation

• Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 139-140

2. Cholestatic Enzymes (Biliary Tract Markers)

ALP (Alkaline Phosphatase)

• Located on the canalicular surface of hepatocytes
• Elevated in biliary obstruction (intrahepatic or extrahepatic), hepatic metastases, infiltrative liver disease
• Most sensitive marker for hepatic metastases among liver chemistry analytes
• Also elevated physiologically in: childhood growth, pregnancy, after a fatty meal (intestinal isoenzyme)
• Elevated in bone disease (osteoblastic activity) - e.g., Paget's disease, fractures
• To confirm hepatic origin: check GGT or 5'-nucleotidase (both elevated if hepatic; normal if bone)
• Decreased in: hypophosphatasia, malnutrition, Wilson disease, hemolysis

GGT (Gamma-Glutamyl Transferase)

• Derived from biliary epithelial cells and hepatocytes
• Highly sensitive for hepatobiliary injury, especially biliary tract
• Used to confirm ALP is of hepatic origin (rises together with ALP in cholestasis)
• Elevated 2-3x ULN in heavy drinkers; elevated in ~70% of chronic alcoholics - used as a marker of recent alcohol consumption
• Also elevated by: warfarin, barbiturates, phenytoin, valproate, methotrexate

5'-Nucleotidase

• Similar hepatic specificity to GGT
• Used as an adjunct to confirm hepatic origin of elevated ALP

• Quick Compendium of Clinical Pathology, 5th ed., p. 2-5

3. Bilirubin

• Quick Compendium of Clinical Pathology, 5th ed., p. 5

4. Synthetic Function Markers

Albumin

• Synthesized exclusively by the liver
• Decreased only when >80% of liver tissue is destroyed
• Low albumin indicates chronic liver disease (cirrhosis, fulminant failure)
• Half-life ~20 days - therefore a better marker of chronic rather than acute liver dysfunction

Prothrombin Time (PT) / INR

• Clotting factors II, V, VII, IX, X are synthesized in the liver
• PT prolonged in acute and chronic liver failure
• Short half-life of factor VII (~6 hours) makes PT a more sensitive and early marker of acute hepatic dysfunction compared to albumin

Ammonia

• Metabolized exclusively by the liver via the urea cycle (Krebs-Henseleit cycle)
• Rises when >80% of liver tissue is destroyed
• Elevated in cirrhosis and fulminant failure - causes hepatic encephalopathy
• Pre-analytical error is common: specimen must be chilled on ice, tested immediately, hemolysis avoided; ammonia rises ~20% per hour after sampling

5. Patterns of LFT Abnormalities by Disease

• Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 140

6. Key Clinical Points

• Isolated ALP elevation with normal GGT = likely bone origin (not liver)
• GGT alone elevated = alcohol, enzyme-inducing drugs
• AST:ALT >2:1 = alcoholic hepatitis
• Very high AST/ALT (>1000 IU/L) = acute viral hepatitis, ischemic hepatitis ("shock liver"), or drug-induced liver injury (e.g., acetaminophen toxicity)
• Normal aminotransferases do not exclude significant liver disease (e.g., cirrhosis, NAFLD)
• Albumin and PT assess synthetic function - the most clinically important markers of severity in chronic liver disease and acute liver failure