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 Hepatitis B with Positive Surface Antigen, Core Antibody, and e-Antigen but Undetectable HBV DNA

For a patient with positive HBsAg, positive anti-HBc, positive HBeAg, undetectable HBV DNA, and normal LFTs, the next step is to perform non-invasive assessment of liver fibrosis (transient elastography/FibroScan), schedule follow-up every 3 months with ALT monitoring and HBV DNA quantification, and consider liver ultrasound to assess for signs of chronic liver disease. 1

Initial Assessment

1. Serological Interpretation:

   • The patient has chronic HBV infection (HBsAg-positive, anti-HBc-positive) 2
   • Positive HBeAg typically indicates active viral replication, but this conflicts with undetectable HBV DNA 1
   • This unusual pattern (HBeAg+ with undetectable DNA) requires careful monitoring as it may represent:
     • A temporary remission phase
     • Laboratory error
     • Presence of HBV variants

2. Immediate Diagnostic Steps:

   • Repeat HBV serological testing to confirm results
   • Perform non-invasive assessment of liver fibrosis (FibroScan) 1
   • Order liver ultrasound to assess for signs of chronic liver disease 1
   • Consider HBV RNA testing if available (may detect transcriptional activity when DNA is undetectable) 3

Monitoring Plan

1. Short-term Follow-up:

   • Schedule follow-up every 3 months for the first year 1
   • Monitor:
     • ALT levels
     • HBV DNA quantification (using sensitive assay)
     • HBeAg/anti-HBe status 1

2. Long-term Surveillance:

   • Continue monitoring every 3-4 months for at least one year 1
   • Consider HCC surveillance if patient has additional risk factors (age >40, family history of HCC) 1

Treatment Considerations

1. Current Treatment Decision:

   • Do not initiate antiviral therapy at this time as the patient has:
     • Undetectable HBV DNA
     • Normal LFTs
     • No evidence of advanced fibrosis/cirrhosis (pending assessment) 1

2. Indications for Future Treatment:

   • Initiate antiviral therapy if:
     • HBV DNA becomes detectable
     • ALT becomes elevated
     • Evidence of liver fibrosis develops 1
   • If treatment becomes necessary, use a high-barrier-to-resistance agent (entecavir or tenofovir) 1

Important Considerations and Pitfalls

1. Risk of Reactivation:

   • Despite undetectable HBV DNA, patients with chronic HBV remain at risk for viral reactivation 1
   • Studies show that even with undetectable intrahepatic cccDNA, virologic rebound can occur after cessation of antiviral therapy 4
   • Particular caution is needed if immunosuppressive therapy is planned in the future 2, 1

2. HCC Risk:

   • Patients with chronic HBV remain at risk for HCC even with undetectable HBV DNA 1
   • Risk is higher if cirrhosis developed before achieving undetectable HBV DNA 1

3. Potential Explanations for Discordant Results:

   • False positive HBeAg
   • Very recent viral suppression
   • HBV variants affecting DNA detection but not HBeAg production
   • Ultra-low viral load below detection threshold

4. Patient Education:

   • Educate patient about the importance of long-term monitoring 1
   • Discuss risk of viral reactivation, especially if immunosuppressive therapy is required in the future 1, 5
   • Emphasize importance of follow-up appointments and regular testing

By following this structured approach, you can appropriately manage this patient with an unusual serological profile while ensuring timely detection of any changes that would warrant treatment initiation.