What Are Liver Enzymes?
Liver enzymes are proteins produced by hepatocytes (liver cells) that can be measured in serum and serve as biochemical markers to detect liver injury patterns, cholestasis, and metabolic dysfunction—not necessarily "liver function" itself. 1, 2
Two Main Categories of Liver Enzymes
Hepatocellular Enzymes (Markers of Liver Cell Injury)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the primary enzymes that reflect hepatocellular necrosis or damage 1, 2
- These enzymes leak into the bloodstream when liver cell membranes are damaged or disrupted 2, 3
- ALT is more liver-specific, while AST is also found in cardiac muscle, skeletal muscle, kidneys, and red blood cells 2, 3
Cholestatic Enzymes (Markers of Bile Flow Obstruction)
- Alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and 5'-nucleotidase primarily reflect cholestasis (impaired bile flow) 1, 2
- Elevated ALP requires GGT measurement to confirm hepatic origin, as ALP can also come from bone, intestine, or placenta 1, 4
- GGT elevation alone indicates enzyme induction rather than cellular damage and is not a marker of liver injury by itself 1
Clinical Patterns of Liver Enzyme Elevation
The pattern of enzyme elevation guides diagnosis using the R ratio: (ALT/ULN) ÷ (ALP/ULN) 1:
- Hepatocellular pattern (R ≥5): Predominant ALT/AST elevation suggests viral hepatitis, drug-induced liver injury, autoimmune hepatitis, or ischemic hepatitis 1
- Cholestatic pattern (R ≤2): Predominant ALP elevation (≥2× ULN with elevated GGT) suggests bile duct obstruction, primary biliary cholangitis, or infiltrative diseases 1, 4
- Mixed pattern (R >2 and <5): Intermediate elevation of both enzyme types 1
Important Distinction: Enzymes vs. Function Tests
Liver enzymes do not measure liver function—they measure liver injury. 1 True liver function is assessed by: 1
- Albumin: Reflects synthetic capacity (produced only in the liver) 1
- Prothrombin time (PT)/INR: Reflects production of clotting factors (requires >70% loss of synthetic function to become abnormal) 1
- Bilirubin: Reflects the liver's ability to conjugate and excrete bile pigments 1
- Platelets: Thrombocytopenia indicates advanced liver disease with portal hypertension and splenic sequestration 1
Clinical Significance Beyond Liver Disease
Aminotransferases (ALT/AST) are increasingly recognized as surrogate biomarkers of metabolic functioning rather than just cellular damage 5:
- Strong predictors of type 2 diabetes, coronary heart disease, and metabolic syndrome 5
- Reflect key aspects of liver metabolic physiology and pathophysiology 5
- Regulation of aminotransferase activity is a complex, highly regulated trait involving multiple genetic and metabolic pathways 5
Common Pitfalls in Interpretation
- Elevated enzymes don't always mean primary liver disease: Extrahepatic conditions (muscle injury, thyroid disease, celiac disease) can cause similar elevations 6, 7
- Normal enzymes don't exclude significant liver disease: Patients with cirrhosis or advanced fibrosis may have normal or near-normal enzyme levels 1
- Isolated GGT elevation is not diagnostic of liver injury: It indicates enzyme induction from alcohol, medications, or metabolic conditions 1
- AST can be elevated from non-hepatic sources: Check creatine kinase (CK) to exclude muscle origin if AST is disproportionately elevated compared to ALT 6