What do elevated Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALK Phos) indicate?

What AST, ALT, and Alkaline Phosphatase Tell You

Primary Diagnostic Information

These three liver enzymes provide distinct information about the pattern and location of liver injury: ALT and AST indicate hepatocellular (liver cell) damage, while alkaline phosphatase signals cholestatic (bile flow) problems. 1

ALT (Alanine Aminotransferase)

ALT is the most specific marker for liver injury because it is concentrated primarily in the liver with minimal presence in other tissues like skeletal muscle and kidney. 1, 2

• Normal ranges differ by sex: 29-33 IU/L in men and 19-25 IU/L in women 1, 2
• Elevations are classified as: mild (<5× upper limit of normal), moderate (5-10× ULN), or severe (>10× ULN) 1, 3
• Common causes of ALT elevation include: nonalcoholic fatty liver disease (NAFLD), viral hepatitis (B, C), medication-induced liver injury, autoimmune hepatitis, hemochromatosis, Wilson disease, and alpha-1 antitrypsin deficiency 1

AST (Aspartate Aminotransferase)

AST is less specific for liver injury than ALT because it is also present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells. 1, 4

• AST elevations can indicate: liver disease, myocardial infarction, skeletal muscle injury, hemolysis, or kidney disorders 1
• The AST:ALT ratio provides diagnostic clues: a ratio >2 suggests alcoholic liver disease, while a ratio <1 is typical of NAFLD, viral hepatitis, or medication-induced injury 2
• When AST is elevated without ALT elevation, consider checking creatine kinase to rule out muscle disorders as the source 2

Alkaline Phosphatase (ALP)

Elevated ALP indicates cholestatic liver disease or bone disorders, as this enzyme is produced in the liver's biliary epithelium and in bone. 1

• Cholestatic causes include: bile duct obstruction (stones, strictures, tumors), primary biliary cholangitis, primary sclerosing cholangitis, drug-induced cholestasis, infiltrative diseases (sarcoidosis, amyloidosis, metastases) 1
• Non-hepatic causes include: bone disease (Paget's disease, fractures, metastases), pregnancy (placental production), and physiologic elevation in children (bone growth) 1
• Gamma-glutamyl transpeptidase (GGT) helps confirm hepatic origin: concomitantly elevated GGT indicates the ALP is from the liver rather than bone 1

Pattern Recognition for Diagnosis

The R value (ratio) distinguishes hepatocellular from cholestatic injury: R = (ALT/ULN) ÷ (ALP/ULN) 1

• Hepatocellular pattern (R ≥5): predominantly elevated ALT/AST with minimal ALP elevation, suggesting direct liver cell damage 1
• Cholestatic pattern (R ≤2): predominantly elevated ALP with minimal ALT/AST elevation, suggesting bile flow obstruction 1
• Mixed pattern (R >2 and <5): both hepatocellular and cholestatic features present 1

Important Clinical Pitfall

When both ALT/AST and ALP are significantly elevated, distinguishing between patterns becomes difficult, and concurrent liver diseases should be suspected. 5 In hepatocellular disease with ALT >10× ULN, median ALP can reach 1.15× ULN, while in cholestatic disease with ALP >5× ULN, ALT can reach 4.57× ULN. 5

Synthetic Function vs. Injury Markers

ALT, AST, and ALP indicate liver injury but not liver function. 1 Actual markers of hepatocellular synthetic function include albumin and prothrombin time/INR, which decrease only in advanced liver disease. 1, 2

When to Pursue Further Evaluation

Moderate to severe elevations (ALT/AST >5× ULN or ALP >2× ULN with elevated GGT) warrant immediate investigation including viral hepatitis serologies, autoimmune markers, medication review, and abdominal ultrasound. 1, 2

Persistent mild elevations (>6 months) require hepatology referral even without severe elevations, as this may indicate chronic progressive liver disease. 2