What is the next test for someone with a positive Hepatitis B (HB) core antibody and a negative Hepatitis B (HB) surface antibody?

HBV DNA Testing is the Next Step for Positive Hepatitis B Core Antibody with Negative Surface Antibody

For patients with a positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antibody (anti-HBs), HBV DNA testing should be performed to determine if chronic HBV infection is present. 1, 2

Interpretation of Serologic Pattern

• The pattern of positive anti-HBc with negative anti-HBs can indicate several clinical scenarios:

  • Resolved past HBV infection with waning anti-HBs levels below detection threshold 3
  • Occult hepatitis B infection (OBI) with low-level HBV replication 1
  • False-positive anti-HBc test result 1
  • Window period during acute HBV infection (rare) 1

• This serologic pattern requires further investigation as it may represent chronic infection that could lead to liver disease progression 1, 3

Diagnostic Algorithm

1. HBV DNA testing should be performed to determine if there is active viral replication 1, 2

   • If HBV DNA is positive: This confirms chronic HBV infection 1
   • If HBV DNA is negative: This suggests resolved infection with loss of detectable anti-HBs or false-positive anti-HBc 3

2. Liver function tests should be performed to assess for liver inflammation 1

   • Elevated ALT/AST may indicate active hepatitis 1
   • Normal liver enzymes may suggest inactive carrier state or resolved infection 1

Management Based on HBV DNA Results

• If HBV DNA is positive:

  • Patient should be evaluated for chronic hepatitis B with liver biopsy if there is persistent or intermittent elevation in aminotransferase levels 1
  • Treatment may be indicated depending on viral load, ALT levels, and evidence of liver damage 1

• If HBV DNA is negative:

  • Consider hepatitis B vaccination, as recommended by KASL guidelines 1
  • Monitor liver function tests periodically 1

Special Considerations

• Immunosuppression risk: Patients with this serologic profile are at risk for HBV reactivation if they undergo immunosuppressive therapy 2

  • Pre-emptive antiviral therapy may be needed if immunosuppression is planned 2, 3

• Occult HBV infection: Some patients may have HBV DNA in the liver despite negative serum HBV DNA 1, 2

  • This is more common in patients with chronic liver disease from other causes 4

Common Pitfalls

• Relying solely on serologic markers without HBV DNA testing can miss cases of chronic infection 1, 3
• Assuming negative HBV DNA completely rules out infection (may need repeat testing in some cases) 2
• Failing to recognize the risk of reactivation in patients undergoing immunosuppression 2, 3

Prevention Strategies

• Hepatitis A vaccination is recommended for patients with evidence of HBV infection to prevent additional liver injury 1
• Sexual and household contacts of HBV carriers should be tested and vaccinated if negative for HBV markers 1
• Counseling regarding prevention of transmission is essential 1