What test do I order to check a patient's hepatitis B (hep B) titers?

Hepatitis B Titer Testing

Order hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc) to check hepatitis B titers. 1

Standard Testing Panel

The most recent AGA guidelines (2025) explicitly recommend this three-test panel as the baseline serologic assessment for hepatitis B status 1:

• HBsAg - Identifies active infection (acute or chronic) 1
• Anti-HBs - Indicates immunity from vaccination or past cleared infection 1
• Total anti-HBc - Distinguishes natural infection from vaccine-induced immunity 1

This testing strategy aligns with universal CDC screening guidance for all adults aged 18 years and older 1.

Interpretation Algorithm

If all three tests are negative:

• Patient is susceptible to HBV infection and needs vaccination 1, 2

If anti-HBs positive, anti-HBc negative, HBsAg negative:

• Patient has vaccine-induced immunity 2, 3

If anti-HBs positive, anti-HBc positive, HBsAg negative:

• Patient has immunity from past infection that has cleared 1, 2, 3

If HBsAg positive:

• Patient has active HBV infection (acute or chronic) 1
• Add HBV-DNA viral load testing to assess replication status 1
• Consider IgM anti-HBc to distinguish acute from chronic infection 1

If isolated anti-HBc positive (HBsAg negative, anti-HBs negative):

• This pattern requires careful interpretation 2
• May represent: (1) window period of acute infection, (2) waning anti-HBs after remote infection, or (3) occult hepatitis B 1, 2
• Repeat testing in 3-6 months and consider HBV-DNA testing 1, 2

Common Pitfalls to Avoid

Do not order only HBsAg and anti-HBs - This misses the window period of acute infection when HBsAg has cleared but anti-HBs has not yet developed 1

Do not order only HBsAg and anti-HBc - This fails to identify susceptible patients who need vaccination 1

Do not order anti-HBc alone - This is insufficient for screening and cannot distinguish between different immunity patterns 3

Do not order HBeAg initially - This test assesses infectivity in known HBV carriers but is not part of initial screening 1

Additional Testing Considerations

For patients with confirmed chronic HBV (HBsAg positive >6 months), add 1:

• HBeAg/anti-HBe - Assesses viral replication phase 1
• HBV-DNA quantitative - Measures viral load 1
• ALT/AST - Evaluates liver inflammation 1

For suspected acute infection, add IgM anti-HBc to the standard panel 1, 4

In immunocompromised patients or those on immunosuppressive therapy, the same three-test panel (HBsAg, anti-HBs, anti-HBc) should be ordered before initiating therapy to stratify reactivation risk 1