What does a non-reactive Hepatitis B (HBV) surface antigen and reactive Hepatitis B (HBV) core antibody indicate?

Interpretation of Hepatitis B Surface Antigen Non-reactive & Reactive Hepatitis B Core Antibody

A non-reactive hepatitis B surface antigen (HBsAg) with a reactive hepatitis B core antibody (anti-HBc) most likely indicates resolved past hepatitis B virus (HBV) infection with natural immunity. 1

Serologic Pattern Interpretation

• This serologic pattern (HBsAg negative, anti-HBc positive) typically indicates previous exposure to HBV that has resolved, with clearance of the virus from the bloodstream 1
• The hepatitis B core antibody appears during acute HBV infection and remains detectable for life, indicating acute, recent, or previous HBV infection 1
• To complete the interpretation, testing for hepatitis B surface antibody (anti-HBs) is recommended to determine immunity status 1

Clinical Significance

• This pattern suggests the patient has recovered from a previous HBV infection and is not currently infectious 1
• Individuals with this serologic pattern are generally not at risk for developing chronic HBV infection 1
• However, these individuals may be at risk for HBV reactivation if they become immunosuppressed, particularly with certain treatments like anti-CD20/CD52 monoclonal antibodies or high-dose corticosteroids 1

Additional Testing Recommendations

• Testing for anti-HBs should be performed to confirm immunity status 1
• If anti-HBs is positive (≥10 mIU/mL), this confirms immunity from past natural infection 1, 2
• If anti-HBs is negative, the patient may be in a "window period" or have low-level chronic infection; HBV DNA testing is recommended to rule out occult HBV infection 1, 3
• Liver function tests should be considered to assess for any ongoing liver inflammation 1

Risk of HBV Reactivation

• Patients who are HBsAg negative but anti-HBc positive have a 3-45% risk of HBV reactivation when receiving immunosuppressive therapy 1
• The risk varies based on:
  • Virological profile (presence of HBV DNA) 1
  • Type of immunosuppressive regimen (higher with rituximab and other anti-CD20 therapies) 1
  • Underlying disease (higher in hematologic malignancies) 1
• Serum HBV DNA testing before starting immunosuppressive therapy helps define reactivation risk 1

Management Considerations

• For immunocompetent individuals without plans for immunosuppression, no specific treatment is typically needed 1
• For patients requiring immunosuppressive therapy:
  • HBV DNA testing is recommended before starting therapy 1
  • If viremic, antiviral prophylaxis similar to HBsAg-positive patients should be considered 1
  • Prophylaxis may be required even with undetectable HBV DNA for high-risk immunosuppressive regimens 1
• Monitoring of liver function tests is recommended during immunosuppressive therapy 1

Important Caveats

• False-negative HBsAg results can occur in patients with chronic liver disease 1
• The absence of anti-HBs does not rule out past infection; some patients lose detectable anti-HBs over time while maintaining anti-HBc positivity 1
• Rarely, isolated anti-HBc positivity can represent a false-positive result, especially in low-prevalence populations 4
• Delayed appearance of anti-HBc can occur in immunocompromised patients, complicating interpretation 5

Remember that this serologic pattern requires careful interpretation in the context of the patient's clinical history, risk factors, and planned medical interventions, particularly immunosuppressive therapies.