What is the next step if Hepatitis B (HB) core antibody is positive?

Next Steps After Positive Hepatitis B Core Antibody Test

When a patient tests positive for hepatitis B core antibody (anti-HBc), the next step should be to test for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) to determine the patient's complete hepatitis B status. 1

Interpreting Serological Patterns

The interpretation of hepatitis B serological markers follows this algorithm:

1. Complete the serological panel:

   • Test for HBsAg and anti-HBs if not already done
   • These three markers together (anti-HBc, HBsAg, anti-HBs) provide a complete picture of hepatitis B status

2. Interpret the pattern based on results:

   HBsAg	Total anti-HBc	Anti-HBs	Interpretation
   Positive	Positive	Negative	Chronic HBV infection
   Negative	Positive	Positive	Resolved past infection with immunity
   Negative	Positive	Negative	Several possibilities (see below)

3. For isolated anti-HBc positive (negative HBsAg, negative anti-HBs):

   • This pattern could indicate 1, 2:
     • Resolved past infection with waning anti-HBs levels
     • False-positive anti-HBc test result
     • "Window period" of acute infection
     • Occult HBV infection with low-level viral replication

Management Algorithm

Based on the complete serological pattern:

If HBsAg positive + anti-HBc positive:

• Indicates chronic HBV infection
• Further evaluate with:
  • Liver function tests (ALT, AST, bilirubin, albumin, prothrombin time)
  • HBV DNA quantification
  • HBeAg and anti-HBe testing
  • Consider liver biopsy if abnormal liver enzymes 3
  • Assess for hepatitis D coinfection 1

If anti-HBs positive + anti-HBc positive (HBsAg negative):

• Indicates resolved infection with natural immunity
• No specific treatment needed
• Counsel regarding prevention of transmission to others
• Monitor periodically if patient will receive immunosuppressive therapy 1

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

1. Test for HBV DNA to rule out occult HBV infection 1
2. Consider hepatitis B vaccination with follow-up anti-HBs testing:
   • An anamnestic response (rapid rise in anti-HBs within 2 weeks) suggests prior resolved infection 4
   • Normal response to complete vaccination suggests the initial anti-HBc was likely a false positive 4
   • No response to vaccination may indicate chronic low-level infection

Special Considerations

• Immunosuppression risk: Patients with positive anti-HBc who will undergo immunosuppressive therapy (especially with anti-CD20 monoclonal antibodies) require prophylactic antiviral therapy to prevent HBV reactivation 1

• Household and sexual contacts: Should be screened for HBV (HBsAg and anti-HBs) and vaccinated if negative 1

• False positives: Isolated anti-HBc can be a false positive result in up to 41% of cases, which can be determined through vaccination response 4

• Occult HBV infection: Present in 1-20% of anti-HBc positive individuals, particularly important to identify before immunosuppressive therapy 1

Common Pitfalls to Avoid

• Don't assume isolated anti-HBc always indicates past infection - multiple interpretations are possible
• Don't forget to test for HBV DNA when anti-HBc is positive but HBsAg is negative in immunocompromised patients
• Don't overlook the need for hepatitis B vaccination in susceptible household and sexual contacts
• Don't miss the opportunity to identify occult HBV infection before immunosuppressive therapy

Following this systematic approach will ensure appropriate management of patients with positive hepatitis B core antibody results, reducing morbidity and mortality from potential HBV reactivation or progression.