What does a positive Hepatitis B (HBV) surface antibody and negative Hepatitis B surface antigen result indicate?

Hepatitis B Surface Antibody Positive and Surface Antigen Negative

A positive hepatitis B surface antibody (anti-HBs) with negative hepatitis B surface antigen (HBsAg) indicates immunity to hepatitis B virus, either from successful vaccination or recovery from a past natural infection. 1

Interpretation of This Serologic Pattern

This combination means you are protected against hepatitis B infection and are not currently infected or infectious. 1 The anti-HBs antibody level of ≥10 mIU/mL is considered protective against HBV infection. 1

To fully understand the source of immunity, you need to check one additional test:

• If hepatitis B core antibody (anti-HBc) is NEGATIVE: Immunity is from vaccination 1
• If hepatitis B core antibody (anti-HBc) is POSITIVE: Immunity is from resolved natural infection 1

The anti-HBc distinction matters because it tells you whether the person was ever actually infected with hepatitis B (the core antibody appears during infection and remains for life). 2

Clinical Significance

Individuals with this serologic profile are protected and cannot transmit HBV to others. 1 They generally do not require hepatitis B vaccination if anti-HBs is documented positive. 1

Important Caveat for Anti-HBc Positive Patients

If the person is anti-HBc positive (meaning past natural infection), there is a critical risk to consider: HBV reactivation can occur if they become immunosuppressed. 2 This risk is particularly high with:

• Anti-CD20/CD52 monoclonal antibodies 2
• High-dose corticosteroids 2
• Other intensive immunosuppressive regimens 2

The reactivation risk in HBsAg-negative, anti-HBc-positive patients ranges from 3-45% depending on the immunosuppressive regimen used. 2 However, the presence of anti-HBs provides significant protection even during immunosuppression—one study showed only 1.2% HBV infection rate in anti-HBc(+)anti-HBs(+) patients versus 5.6% in those without anti-HBs after kidney transplantation. 3

Management Recommendations

For Immunocompetent Individuals

• No specific treatment or monitoring is needed 2
• Document the immunity status for future reference 1

For High-Risk Groups Requiring Monitoring

The CDC recommends periodic anti-HBs testing for: 1

• Healthcare workers with ongoing exposure risk
• Other occupationally exposed individuals
• Consider booster vaccination if anti-HBs falls below 10 mIU/mL 1

Before Planned Immunosuppression (If Anti-HBc Positive)

This is where the distinction becomes clinically critical:

1. Check HBV DNA before starting immunosuppressive therapy 2
2. Consider antiviral prophylaxis if viremic or if using high-risk immunosuppression 2
3. Monitor liver function tests during immunosuppressive therapy 2

Research shows that anti-TNF therapy in anti-HBc(+)/HBsAg(-) patients has a low reactivation rate (0.8-2.5%), 4 but fatal reactivations have been documented in patients who were HBsAg-negative/anti-HBc-positive before chemotherapy. 5

Common Pitfalls to Avoid

• Do not assume all anti-HBs positivity is protective: Passively acquired antibody from recent blood product transfusion can cause false reassurance—this antibody does not confer true immunity. 6 If recent transfusion occurred, retest after several weeks.

• Do not miss screening close contacts: If this represents resolved natural infection (anti-HBc positive), household and sexual contacts should be screened and vaccinated if susceptible. 7

• Do not forget about HBV reactivation risk: In anti-HBc-positive patients requiring immunosuppression, failure to recognize reactivation risk can be fatal. 5 Always check HBV DNA and consider prophylaxis before starting therapy. 2

• Do not overlook variant strains: HBV surface antigen variants can escape detection in standard assays while still being infectious, potentially causing diagnostic confusion. 8