What does a negative Hepatitis B (HBV) surface antibody test result mean?

What Does a Negative Hepatitis B Surface Antibody Mean?

A negative hepatitis B surface antibody (HBsAb or anti-HBs) test indicates you lack detectable antibodies against hepatitis B virus and are not immune to HBV infection. 1

Primary Interpretation

A negative HBsAb result means one of the following:

• You have never been infected with HBV and never been vaccinated - This is the most common scenario for a negative result 1
• You were previously vaccinated but did not develop sufficient antibody response - This occurs in a subset of vaccine recipients who are "non-responders" 1
• Your antibody levels have waned below detectable levels - Even after successful vaccination, antibody titers can decline over time, though cellular immunity may persist 2

The protective threshold for immunity is generally considered to be ≥10 mIU/mL, so any result below this level indicates lack of protective immunity 3, 1, 4

What You Need to Do Next

If You Have Never Been Vaccinated:

• Complete a full hepatitis B vaccination series immediately 1
• The standard series consists of 3 doses given at 0,1, and 6 months 4
• Alternative vaccines include HEPLISAV-B (2-dose series) or other FDA-approved formulations 2

If You Were Previously Vaccinated:

• Receive one challenge dose of hepatitis B vaccine if you have documentation of a complete prior vaccination series 2
• Complete a full revaccination series if you have no documentation of prior vaccination 2

Post-Vaccination Testing:

• Check anti-HBs levels 1-2 months after completing the vaccination series to confirm protective immunity (≥10 mIU/mL) 1, 2
• This timing is critical because testing too early may show falsely low levels 2

Additional Testing to Consider

To fully understand your hepatitis B status, you should also be tested for:

• Hepatitis B surface antigen (HBsAg) - To rule out current active infection 1
• Hepatitis B core antibody (anti-HBc total) - To determine if you had previous exposure to HBV 1

This complete serologic profile helps distinguish between:

• Never infected/never vaccinated (HBsAg negative, anti-HBs negative, anti-HBc negative)
• Immune due to natural infection (HBsAg negative, anti-HBs positive, anti-HBc positive) 3
• Immune due to vaccination (HBsAg negative, anti-HBs positive, anti-HBc negative) 3
• Chronically infected (HBsAg positive, anti-HBs negative, anti-HBc positive) 3

Special Populations Requiring Attention

Healthcare Workers:

• Testing for anti-HBs upon hire is recommended for those with documented hepatitis B vaccination 1
• Those with anti-HBs <10 mIU/mL should receive additional vaccine doses 1

Immunocompromised Individuals:

• May require higher vaccine doses and more frequent monitoring 1
• Include patients on chemotherapy, anti-CD20 antibodies (rituximab), high-dose corticosteroids, or with underlying malignancies 3
• These patients are at higher risk of vaccine non-response 2

Sexual Partners of HBsAg-Positive Persons:

• Should receive immediate vaccination with the first dose given at the time of blood collection for serologic testing 1

Pregnant Women:

• All pregnant women should be screened for HBsAg to identify those who could transmit infection to their infants 4

Important Caveats and Pitfalls

False-Positive Scenarios to Avoid:

• Passively acquired antibodies from blood products can cause temporary positive anti-HBs results that do not indicate true immunity 5, 6
• This is particularly relevant in patients who recently received fresh frozen plasma, immunoglobulin products, or Rho(D) immune globulin 5

Window Period Consideration:

• During acute HBV infection, there is a "window period" when HBsAg has disappeared but anti-HBs is not yet detectable 3
• During this window, IgM anti-HBc is the only detectable marker and indicates acute or recent infection 3

Assay Variability:

• Different laboratory assays may have different cutoff values for determining positive versus negative results 1
• Results should always be interpreted in the clinical context

Non-Responders to Vaccination:

• Approximately 5-10% of healthy adults do not develop protective antibody levels after a complete vaccine series 2
• Risk factors for non-response include older age, obesity, smoking, immunosuppression, and chronic medical conditions 2

Current Vaccination Recommendations

• Universal hepatitis B vaccination is now recommended for all adults aged 19-59 years by the Advisory Committee on Immunization Practices 2
• Vaccination is also recommended for all persons from birth to age 18 4
• High-risk adults of any age should be vaccinated, including healthcare workers, people with multiple sexual partners, injection drug users, and household contacts of HBsAg-positive persons 3