What is the laboratory workup for hepatitis?

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Last updated: September 25, 2025 • View editorial policy

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Laboratory Workup for Hepatitis

The essential laboratory workup for hepatitis includes liver function tests (AST, ALT, bilirubin), hepatitis viral markers, and additional tests based on suspected etiology. 1, 2

Initial Laboratory Tests

Core Tests

  • Liver function tests:
    • Alanine aminotransferase (ALT)
    • Aspartate aminotransferase (AST)
    • Total and direct bilirubin
    • Alkaline phosphatase (ALP)
    • Gamma-glutamyl transferase (GGT)
    • Albumin
    • Total protein and globulin/gamma-globulin/IgG levels

Viral Hepatitis Markers

  • Hepatitis B:

    • Hepatitis B surface antigen (HBsAg)
    • Hepatitis B core antibody (HBcAb) - total and IgM
    • Hepatitis B surface antibody (HBsAb)
    • If positive for HBsAg: HBeAg, HBeAb, and HBV DNA quantification 2

  • Hepatitis A:

    • Anti-HAV IgM (for acute infection)
    • Anti-HAV total (for past infection/immunity)

  • Hepatitis C:

    • Anti-HCV antibody
    • If positive: HCV RNA quantification

  • Other viral hepatitis markers as clinically indicated:

    • Hepatitis D (if HBsAg positive)
    • Hepatitis E

Additional Tests Based on Clinical Suspicion

Autoimmune Hepatitis Workup

  • Immunoglobulin G (IgG) level
  • Autoantibodies:
    • Antinuclear antibody (ANA)
    • Smooth muscle antibody (SMA)
    • Liver-kidney microsomal antibody (anti-LKM-1) 1

Drug-Induced or Toxic Hepatitis

  • Detailed medication and supplement history
  • Alcohol consumption history
  • Drug levels when applicable

Other Etiologies

  • Ceruloplasmin (Wilson's disease)
  • Iron studies (hemochromatosis)
  • Alpha-1 antitrypsin level
  • Complete blood count (CBC)
  • Comprehensive metabolic panel

Imaging Studies

  • Ultrasound of the liver (to assess for structural abnormalities, biliary obstruction)
  • CT or MRI may be indicated based on clinical presentation

Liver Biopsy Considerations

  • Consider liver biopsy for:
    • Unclear etiology after initial workup
    • Suspected autoimmune hepatitis
    • Assessment of disease severity/fibrosis
    • Steroid-refractory cases 1

Interpretation of Results

Patterns of Liver Enzyme Elevation

  • Hepatocellular pattern: Predominant elevation of aminotransferases (AST, ALT)
    • Viral hepatitis, autoimmune hepatitis, drug-induced liver injury
  • Cholestatic pattern: Predominant elevation of alkaline phosphatase, GGT
    • Biliary obstruction, drug-induced cholestasis, primary biliary cholangitis
  • Mixed pattern: Elevation of both aminotransferases and cholestatic enzymes

Key Diagnostic Indicators

  • ALT/AST < 30 IU/L typically excludes significant hepatic inflammation with 96% certainty 3
  • GGT is the most sensitive test for liver disease with fewest false negatives 4
  • Direct bilirubin is the most specific test for liver disease 4

Special Considerations

  • Hepatitis B testing is essential before initiating anti-CD20 monoclonal antibody-based regimens due to risk of reactivation 1
  • Hepatitis C testing is needed in high-risk patients and patients with splenic marginal zone lymphoma 1
  • In immune checkpoint inhibitor therapy, monitor liver enzymes before each infusion and consider weekly monitoring if grade 1 LFT elevations are present 1

Common Pitfalls to Avoid

  • Relying solely on aminotransferases, which can be normal in chronic liver disease
  • Failing to test for viral hepatitis in patients with abnormal liver tests
  • Not considering drug-induced liver injury in the differential diagnosis
  • Overlooking autoimmune hepatitis, which requires specific antibody testing
  • Neglecting to quantify viral load in chronic viral hepatitis, which is crucial for treatment decisions

Remember that abnormal liver function tests should prompt a systematic evaluation to determine the underlying cause of hepatitis, as proper diagnosis guides appropriate management and improves outcomes.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Hepatitis B Infection

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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