Abnormal Liver Tests

General Overview

  • Hepatocellular pattern
    • Disproportionate elevation of AST and ALT compared with alkaline phosphatase
    • AST : ALT >2 (with elevated GGT), consider Alcohol
  • Cholestatic pattern
    • Disproportionate elevation in alkaline phosphatase compared with AST and ALT
      • Painful (stone/infection) vs. painless (tumour)
  • Mixed pattern
  • Isolated hyperbilirubinemia (with normal serum AST/ALT/ALP)

R ratio

    • R > 4 Hepatocellular injury
    • R < 2 Cholestatic injury
    • R 2-5 Mixed pattern
    • Note: All of these patterns may have elevated bilirubin

Causes of elevated AST/ALT

  • Hepatic
    • Alcoholic liver disease <8xULN
    • NAFLD (steatosis, NASH) <4xULN
    • Ischemic hepatitis >50xULN
    • Acute viral hepatitis >20xULN
    • Chronic viral hepatitis
    • Hemochromatosis
    • Wilson’s Disease
    • Alpha 1 antitrypsin deficiency
    • Liver trauma
    • HELLP syndrome
    • Drug-induced liver injury
    • Autoimmune hepatitis
  • Non-hepatic
    • Skeletal muscle damage/ rhabdomyolysis
    • Cardiac muscle damage
    • Thyroid disease
    • Strenuous exercise
    • Hemolysis
    • Adrenal insufficiency
    • Celiac disease
    • Malignant infiltration (breast cancer, small cell lung cancer, lymphoma, melanoma, myeloma)

Management of elevated AST/ALT

  • History, Physical
    • Risk of fatty liver, viral hepatitis
    • Signs of liver failure
  • Discontinue hepatotoxic medications and alcohol
  • Find underlying cause:
  1. CBC/platelet, AST/ALT, Alk Phos, Total Bili, Albumin, PT/INR
  2. HBsAg, HBcAb, HBsAb, HCV Ab (with PCR if positive), iron panel, abdominal ultrasound r/o fatty liver
    • If mild elevation and history of alcohol consumption, can repeat initial testing after 3-6 months before moving on to additional testing
  3. Autoimmune: ANA, ASMA, Anti-LKM, IgG
  4. Ceruloplasmin (Wilson), Anti-TTG (with total IgA), TSH, alpha-1 antitrypsin level (phenotyping if indicated)
  5. May consider muscle disorder (CK or aldolase), tick-borne, adrenal insufficiency
  6. Refer to hepatologist for liver biopsy
    • If mild elevation may consider expectant management rather than referral
    • Refer immediately of acute liver failure for possible transplant
  • If severe elevation, add
    • bhCG (r/o HELLP)
    • HAV IgM Ab, Hep C Viral RNA,
    • HSV Ab, VZV Ab, EBV, CMV Ag,
    • Serum drug panel (consider n-acetyl cysteine for tylenol), urine toxicology
    • Abdominal Doppler US (r/o vascular obstruction/Budd-Chiari syndrome)

Elevated Alkaline Phosphatase

  • r/o pregnancy, r/o postprandial (<2x ULN, repeat 12h fasting)
  • Elevated GGT confirms hepatic
    • RUQ ultrasonography
      • Common obstructive causes:
        • Intrahepatic (absence of dilatation)
          • PBC, PSC, infiltrative disease, drug (androgenic steroids, phenytoin)
        • Extrahepatic (biliary dilatation)
  • If GGT low, consider bone/placenta (pregnancy)
    • Calcium, PTH, 25-hydroxy Vit D, Bone scan

Isolated GGT

  • Elevated GGT with normal liver biochemical tests including ALP should not lead to an exhaustive work-up


  • Jaundice usually hyperbilirubinemia
    • If normal bilirubin, consider carotenemia

see Jaundice in pediatrics

Causes of elevated bilirubin

  • Unconjugated hyperbilirubinemia
    • Overproduction (hemolysis)
      • Hypersplenism
      • G6PD, Thalassemia, Sickle cell, spherocytosis, elliptocytosis, malaria
      • Drug-induced/auto-immune
    • Impaired hepatic uptake
      • Portosystemic shunt
      • Drugs (Rifampin)
    • Impaired conjugation
      • Hyperthyroidism, hepatitis, Wilson's
      • Gilbert or Crigler-Najar (LFT normal, no evidence of hemolysis/sepsis)
        • History of jaundice during stress/fasting
    • Stressor (sepsis) may act on all the above
  • Conjugated hyperbilirubinemia
    • Elevated ALP/GGT
      • Biliary obstruction (eg, gallstones, tumor)
    • Elevated ALT/AST
      • Liver disease causing hepatocellular dysfunction (eg, hepatitis, sepsis, or hepatotoxic drugs)
    • Normal ALP/GGT
      • Inherited disorders (eg, Dubin Johnson or Rotor syndrome)


  • CBC
  • LFT
  • INR, albumin
  • Hemolytic work-up
    • Reticulocytes
    • Haptoglobin
    • LDH
    • Smear
    • Coomb's
  • Family History consider G6PD screen