What labs should be ordered to evaluate liver function?

Standard Laboratory Tests for Liver Function Evaluation

The standard laboratory panel for evaluating liver function should include alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin (total and direct), albumin, and prothrombin time/INR. 1

Core Liver Function Tests

• Hepatocellular injury markers:

  • ALT - More specific for liver injury due to low concentrations in other tissues 1
  • AST - Can be elevated in disorders involving heart, skeletal muscle, kidneys, and other tissues 1

• Cholestatic markers:

  • ALP - Elevated in cholestatic liver diseases; can be of non-hepatic origin 1
  • GGT - Confirms hepatic origin of ALP elevation and is the most sensitive test for liver disease 1, 2

• Bilirubin (total and direct) - Elevated in both hepatocellular and cholestatic diseases 1

• Synthetic function markers:

  • Albumin - Reflects liver's synthetic capacity 1
  • Prothrombin time/INR - Evaluates coagulation function and helps differentiate between acute and chronic liver disease 1, 3

• Complete blood count with platelets - Decreased platelets may indicate portal hypertension or advanced liver disease 1

Classification of Abnormalities

• Hepatocellular pattern: Disproportionate elevation of AST and ALT compared to ALP 4

  • Mild: <5× upper limit of normal
  • Moderate: 5-10× upper limit of normal
  • Severe: >10× upper limit of normal 1

• Cholestatic pattern: Disproportionate elevation of ALP compared to AST and ALT 4

• Mixed pattern: Elevations in both hepatocellular and cholestatic markers 4, 5

Additional Tests Based on Initial Findings

• For viral hepatitis evaluation:

  • Hepatitis B serology (HBsAg, anti-HBc, anti-HBs) 1
  • Hepatitis C antibody and RNA 1
  • Hepatitis A antibody (IgM and IgG) for immunity status 1

• For autoimmune liver disease:

  • Immunoglobulins (IgG, IgM, IgA) 1
  • Autoantibodies (ANA, SMA, anti-LKM, AMA) 1

• For metabolic liver disease:

  • Iron studies (serum iron, ferritin, transferrin saturation) 1, 4
  • Ceruloplasmin (for Wilson's disease) 4
  • Alpha-1 antitrypsin 4

• For fibrosis assessment:

  • Non-invasive fibrosis markers (FIB-4, APRI) 1
  • Consider liver elastography in patients with abnormal liver tests 1

Common Pitfalls and Caveats

• Normal ALT levels are lower than traditionally defined: 29-33 IU/L for men and 19-25 IU/L for women 1, 4

• ALT can be normal even in the setting of cirrhosis; the AST:ALT ratio remains useful even when both values are within normal range 1

• Isolated ALP elevation should be confirmed as hepatic in origin using GGT before pursuing extensive hepatic workup 1, 3

• Screening healthy, asymptomatic individuals with liver function tests may not be cost-effective unless there are specific risk factors 1, 6

• Inflammatory markers (ESR, CRP) may be useful in monitoring certain liver conditions with inflammatory components 7

• Liver tests should be performed during clinical stability for most accurate assessment 1

• Abnormal liver tests require follow-up testing to determine etiology rather than relying solely on pattern recognition 1, 4