What is the management plan for a patient with Hepatitis B surface antigen (HBsAg) positive and Hepatitis B core antibody (HBcAb) negative?

Management of HBsAg Positive with HBcAb Negative Patient

A patient with positive Hepatitis B surface antigen (HBsAg) and negative Hepatitis B core antibody (HBcAb) requires immediate antiviral therapy with a high barrier to resistance agent such as entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF), regardless of viral load or liver enzyme levels. 1

Understanding the Serological Profile

This unusual serological pattern (HBsAg positive, HBcAb negative) represents one of the following scenarios:

• Early acute HBV infection (window period before anti-HBc development)
• False negative HBcAb test
• Immunosuppressed state affecting antibody production
• Rare variant of chronic HBV infection

Diagnostic Workup

1. Confirm the serological profile:

   • Repeat HBsAg and HBcAb testing to rule out laboratory error
   • Test for HBeAg, anti-HBe, and quantitative HBV DNA
   • Check liver function tests (ALT, AST, bilirubin, albumin, prothrombin time)

2. Assess liver status:

   • Liver ultrasound to evaluate for cirrhosis and exclude focal lesions 2
   • Consider liver biopsy if there are abnormal liver enzymes to determine disease stage and fibrosis 1

Treatment Algorithm

Step 1: Initiate Antiviral Therapy

• First-line options (high barrier to resistance):

  • Entecavir 0.5 mg daily
  • Tenofovir disoproxil fumarate (TDF) 300 mg daily
  • Tenofovir alafenamide (TAF) 1

• Avoid lamivudine due to high resistance rates 1

Step 2: Monitoring Response

• Check HBV DNA levels every 3 months until undetectable, then every 3-6 months
• Monitor liver enzymes every 3 months
• Reassess HBV serological markers (including HBcAb) every 6 months 1

Step 3: Long-term Management

• Continue antiviral therapy indefinitely unless serological profile changes significantly
• Annual liver ultrasound for HCC surveillance
• Consider hepatology consultation for specialized management 1

Special Considerations

If Patient Requires Immunosuppressive Therapy

This is particularly important as the unusual serological profile may indicate an immunocompromised state:

• For high-risk immunosuppressive therapy (rituximab, stem cell transplantation):
  • Continue antiviral prophylaxis for at least 12 months after completing immunosuppressive therapy (18 months for rituximab-based regimens) 1
  • Monitor HBV DNA and ALT every 3-6 months during prophylaxis 1

If Patient Has Abnormal Liver Function

• More aggressive monitoring may be required
• Consider liver biopsy to assess disease activity and fibrosis 1

Pitfalls to Avoid

1. Don't assume it's a false positive HBsAg: While unusual, this serological pattern can occur and requires treatment 3

2. Don't use lamivudine for treatment: High resistance rates make it unsuitable for long-term therapy 1

3. Don't delay treatment while investigating: Initiate antiviral therapy promptly while completing the diagnostic workup 1

4. Don't discontinue monitoring after HBV DNA becomes undetectable: Continued surveillance is essential as viral reactivation can occur 1

5. Don't forget HCC surveillance: All HBsAg-positive patients require regular screening for hepatocellular carcinoma, regardless of HBcAb status 1

This unusual serological pattern requires careful management and possibly specialist consultation to ensure optimal outcomes and prevent progression to cirrhosis, liver failure, or hepatocellular carcinoma.