A group of enzymes found throughout the body but produced predominantly in the liver, bones, placenta, and small intestine. Common causes of elevated serum ALP include cholestasis, bone disease (e.g., bone metastases, Paget's disease, hyperparathyroidism), and pregnancy. The normal reference range is 40-120 U/L.

Common causes of elevation

• Cholestasis (obstructive or nonobstructive)
  • When ALP is elevated but γ-GT and AST/ALT ratio are normal, cholestasis is an unlikely cause for the ALP elevation.
• Infiltrative diseases of the liver (e.g., malignancies or amyloidosis)
• Increased osteoblast activity
  • E.g., skeletal metastases, osteomalacia, fracture healing, Paget disease, and during physiological growth periods
• Seminoma
• Pregnancy (third trimester)
• Chronic kidney disease

Differential Diagnosis Based on Elevated LFTs

Hepatocellular pattern: Elevated aminotransferases out of proportion to alkaline phosphatase

• AST/ALT < 1 (AST < ALT) (Also called inflammatory type hepatocellular injury)
  • Uncomplicated viral hepatitis
  • Minor fatty liver disease
  • Extrahepatic cholestasis
• AST/ALT ≥ 1 (AST > ALT) (Also called necrotic type hepatocellular injury)
  • Alcoholic hepatitis
    • Typically AST/ALT > 2
    • AST usually does not exceed 500 U/L in alcoholic hepatitis.
  • Fulminant, necrotic hepatitis
  • (Decompensated) cirrhosis: The AST/ALT ratio can increase as fibrosis advances.
  • Hepatocellular carcinoma, liver metastases
  • Muscle damage
  • Myocardial infarction

Cholestatic pattern: Elevated alkaline phosphatase +gamma glutamyl transferase + bilirubin out of proportion to AST and ALT

• Hepatobiliary causes: Bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, medication-induced, infiltrating diseases of the liver (sarcoidosis, amyloidosis, lymphoma, among others), cystic fibrosis, hepatic metastasis, cholestasis
• Non-Hepatic causes: Bone disease, pregnancy, chronic renal failure, lymphoma or other malignancies, congestive heart failure, childhood growth, infection, or inflammation