What is the recommended test for diagnosing an active Hepatitis B (HBV) infection?

Testing for Active Hepatitis B Infection

The primary test for diagnosing active hepatitis B infection is hepatitis B surface antigen (HBsAg), which should be performed using an FDA-licensed immunoassay with confirmatory neutralizing testing for initially reactive specimens. 1

Initial Diagnostic Approach

Primary Screening Test

• HBsAg is the necessary and accurate test for diagnosis of active HBV infection 1
• A confirmed HBsAg-positive result indicates active HBV infection, either acute or chronic 1
• HBsAg appears 1-10 weeks after exposure and persists beyond 6 months in chronic infection 1

Distinguishing Acute from Chronic Infection

• Acute infection: HBsAg positive + IgM anti-HBc positive 1
• Chronic infection: HBsAg positive for >6 months (IgM anti-HBc typically negative or low-level) 1
• The persistence of HBsAg beyond 6 months is adequate for diagnosing chronic hepatitis B 1

Essential Additional Testing for Active Infection

Viral Replication Markers

Once HBsAg positivity is confirmed, assess the following:

• HBV DNA quantification: Direct measure of viral replication, essential for characterizing infection status and treatment decisions 2
• HBeAg/anti-HBe status:
  • HBeAg positive indicates high viral replication (typically HBV DNA ≥20,000 IU/mL) 1, 2
  • HBeAg negative with anti-HBe positive suggests lower replication (HBV DNA ≥2,000 IU/mL in active disease) 1

Liver Injury Assessment

• ALT/AST levels: Persistent or intermittent elevation indicates active hepatitis requiring treatment consideration 1
• Normal ALT with HBV DNA <2,000 IU/mL suggests inactive carrier state 1

Critical Clinical Pearls

Common Pitfalls to Avoid

• Window period: During acute infection, anti-HBc IgM may be the only detectable marker between HBsAg disappearance and anti-HBs appearance 1
• False acute diagnosis: Patients with chronic HBV exacerbations can test positive for IgM anti-HBc, potentially leading to misdiagnosis as acute infection 2
• Occult infection: Isolated anti-HBc positivity may indicate occult hepatitis B; measure HBV DNA in these cases 1

Laboratory Testing Requirements

• Use FDA-licensed HBsAg tests with neutralizing confirmatory testing for initially reactive specimens 1
• All HBsAg-positive persons should be considered infectious 1

Algorithmic Approach to Interpretation

If HBsAg positive:

1. Check IgM anti-HBc to distinguish acute vs. chronic infection 1
2. Measure HBV DNA to quantify viral replication 2
3. Test HBeAg/anti-HBe to assess replication phase 1
4. Check ALT/AST to determine disease activity 1

If HBsAg negative but clinical suspicion remains:

• Test anti-HBc (total and IgM) to detect window period or occult infection 1
• Consider HBV DNA testing if immunocompromised or unexplained liver enzyme elevation 1