Understanding Hepatitis B Surface Antigen Test Results and Immunity Status
A nonreactive (negative) Hepatitis B surface antigen (HBsAg) test result means the person does not have an active hepatitis B infection, but it alone does not determine immunity status. 1
Interpretation of Hepatitis B Serologic Markers
To properly assess immunity status, multiple serologic markers must be evaluated together:
| HBsAg | Total anti-HBc | IgM anti-HBc | Anti-HBs | Interpretation |
|---|---|---|---|---|
| - | - | - | - | Never infected, susceptible |
| - | - | - | + | Immune due to vaccination |
| - | + | - | + | Resolved past infection and immune |
| + | + | + | - | Acute infection |
| + | + | - | - | Chronic infection |
Key Points About HBsAg Negative Results
- A negative HBsAg test alone only indicates the absence of active hepatitis B virus (HBV) infection
- To determine immunity status, additional testing is required:
- Anti-HBs (antibody to hepatitis B surface antigen)
- Anti-HBc (antibody to hepatitis B core antigen)
Determining Immunity Status
Not immune (susceptible): Negative for HBsAg, anti-HBs, and anti-HBc
- These individuals should receive hepatitis B vaccination
- Monthly screening with HBsAg recommended for high-risk groups like dialysis patients 1
Immune due to vaccination: Negative for HBsAg and anti-HBc, but positive for anti-HBs (>10 mIU/mL)
- No further testing required unless immunosuppressive therapy planned
- Annual screening with anti-HBs recommended for dialysis patients 1
Immune due to natural infection: Negative for HBsAg, positive for anti-HBc and anti-HBs
- These individuals have recovered from a past HBV infection
- They are immune to future HBV infection and not infectious to others 2
Clinical Pitfalls to Avoid
- Don't rely on HBsAg testing alone to determine immunity status - this is insufficient 3
- Don't confuse vaccination immunity with natural infection immunity - they have different serologic patterns and clinical implications 2
- Be aware of the "window period" in acute hepatitis B when HBsAg may be negative but the person is still infected (detectable by anti-HBc IgM) 4
- Consider false-negative HBsAg results which can occur with HBsAg variants 5
Special Considerations
- For patients requiring immunosuppressive therapy, especially anti-CD20 monoclonal antibodies, additional testing for hepatitis B core antibody is essential to prevent reactivation 2
- Patients with chronic liver disease should be screened for both HAV and HBV antibodies before vaccination 3
- Post-vaccination testing is recommended for patients with advanced liver disease due to lower seroconversion rates 3
In summary, a nonreactive HBsAg test alone does not determine immunity status - additional testing for anti-HBs and anti-HBc is required to properly assess whether someone is susceptible, immune due to vaccination, or immune due to resolved natural infection.