What is the next step in managing a patient with positive Hepatitis B (HBV) surface antigen, core antibody, and e-antigen, but undetectable HBV DNA, normal Liver Function Tests (LFTs), and negative Hepatitis C (HCV)?

Management of Positive HBV Surface Antigen with Undetectable HBV DNA and Normal LFTs

The next step in managing this patient with positive HBsAg, HBeAg, and core antibody but undetectable HBV DNA and normal LFTs is to schedule follow-up every 3 months for the first year with ALT monitoring, HBV DNA quantification, and HBeAg/anti-HBe status assessment. 1

Understanding the Patient's HBV Status

This patient's serologic profile suggests they are in a transitional phase of chronic HBV infection. The positive HBsAg confirms chronic infection, while the positive HBeAg typically indicates active viral replication. However, the undetectable HBV DNA creates a discordant pattern that requires careful monitoring and interpretation.

Possible Explanations for This Profile:

1. Fluctuating HBeAg-negative CHB: The patient may be in a temporary remission phase of HBeAg-negative chronic hepatitis B, where viral levels naturally fluctuate 2

2. Precore/Core Promoter Mutations: Consider testing for mutations that can affect HBeAg expression without changing viral replication 1

3. Early Transition Phase: The patient could be in early transition from an immune reactive phase to an inactive carrier state 2

Recommended Management Algorithm

Immediate Next Steps:

1. Schedule regular monitoring:

   • Every 3 months for the first year: ALT, HBV DNA, HBeAg/anti-HBe status 1
   • Continue monitoring for at least one year to detect potential fluctuations in viral activity

2. Perform non-invasive liver fibrosis assessment:

   • Transient elastography (FibroScan)
   • Liver ultrasound to assess for signs of chronic liver disease 1

3. Consider testing for precore/core promoter mutations if the discordant pattern persists 1

Treatment Considerations:

• Do not initiate antiviral therapy at this time as the patient has undetectable HBV DNA and normal LFTs without evidence of advanced fibrosis/cirrhosis 1

• Monitor for spontaneous HBeAg seroconversion, which would be a favorable prognostic sign 1

• Reassess need for treatment if:

  • HBV DNA becomes detectable
  • ALT becomes elevated
  • Evidence of liver fibrosis develops

Long-term Follow-up Plan

• After confirming stability through the first year, monitoring can be extended to every 6 months 1

• Consider HCC surveillance if the patient has additional risk factors (age >40, family history of HCC, cirrhosis) 1

• Educate the patient about:

  • Risk of viral reactivation with immunosuppressive therapy
  • Need for disclosure of HBV status to healthcare providers
  • Importance of long-term monitoring

Important Caveats and Pitfalls

1. Risk of reactivation: Despite undetectable HBV DNA, patients remain at risk for viral reactivation, especially if immunosuppressive therapy is required 1, 3, 4

2. Misinterpreting a single undetectable HBV DNA result: One study showed that patients with undetectable intrahepatic cccDNA still experienced virologic rebound after NUC cessation 5

3. False reassurance: Even with undetectable HBV DNA, patients may still be at risk of HCC, particularly if they developed cirrhosis before achieving undetectable HBV DNA 1

4. Incomplete serological assessment: Ensure complete serological testing has been performed to fully characterize the patient's HBV status 1

By following this structured monitoring approach, you can properly characterize this patient's HBV infection status, detect any changes in viral activity, and determine the appropriate timing for potential antiviral therapy if needed.