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, core antibody, and HBeAg but undetectable HBV DNA and normal LFTs, close monitoring is recommended rather than immediate antiviral therapy, as this represents a unique virological profile that requires further evaluation.

Understanding the Patient's Virological Profile

This patient presents with an unusual serological pattern:

• Positive HBsAg (indicating chronic HBV infection)
• Positive core antibody (confirming HBV exposure)
• Positive HBeAg (typically indicating active viral replication)
• Undetectable HBV DNA (contradicting the HBeAg positivity)
• Normal LFTs (suggesting absence of liver inflammation)
• Negative HCV (ruling out co-infection)

Interpretation of This Pattern

This pattern is atypical because:

• HBeAg positivity usually correlates with high HBV DNA levels
• The discordance between positive HBeAg and undetectable HBV DNA could indicate:
  1. A recent spontaneous viral suppression
  2. Presence of a precore/core promoter mutant virus
  3. Laboratory error in HBV DNA quantification
  4. Very recent initiation of antiviral therapy (not mentioned in history)

Management Algorithm

Step 1: Confirm Results (1-2 weeks)

• Repeat HBV serologies (HBsAg, HBeAg, anti-HBe)
• Repeat HBV DNA quantification using a highly sensitive PCR assay (detection limit ≤10-20 IU/mL) 1
• Confirm normal LFTs (ALT, AST, bilirubin, albumin, INR)

Step 2: Assess Disease Stage (1-2 months)

• Perform non-invasive assessment of liver fibrosis (transient elastography/FibroScan)
• Consider liver ultrasound to assess for signs of chronic liver disease
• If available, quantitative HBsAg levels can provide additional prognostic information

Step 3: Determine Management Based on Confirmed Results

If repeat testing confirms the current pattern:

• Schedule follow-up every 3 months for the first year with:
  • ALT monitoring
  • HBV DNA quantification
  • HBeAg/anti-HBe status 2, 1

If HBV DNA becomes detectable or ALT elevates:

• Initiate antiviral therapy with a high-barrier-to-resistance agent (entecavir or tenofovir)
• The goal of therapy would be to maintain undetectable HBV DNA levels and normalize ALT 2

If the pattern persists with undetectable HBV DNA and normal ALT:

• Continue monitoring every 3-4 months for at least one year
• After stability is confirmed, monitoring can be extended to every 6 months 1

Rationale for This Approach

The KASL guidelines state that "the ultimate treatment goals in patients with HBeAg-positive hepatitis are normalization of the ALT level, undetectable HBV DNA level, and the clearance or seroconversion of HBsAg and HBeAg" 2. However, this patient already has undetectable HBV DNA and normal ALT despite being HBeAg-positive.

The EASL guidelines indicate that "therapy must ensure a degree of virological suppression that will then lead to biochemical remission" 2, which this patient has already achieved without treatment.

Important Considerations

1. HBeAg seroconversion monitoring: Watch for spontaneous HBeAg seroconversion, which would be a favorable prognostic sign 2

2. Risk of reactivation: Despite undetectable HBV DNA, this patient remains at risk for viral reactivation, especially if immunosuppressive therapy is ever required 2, 3

3. HCC surveillance: Consider HCC surveillance if the patient has additional risk factors (age >40, family history of HCC, cirrhosis) 2

4. Precore/core promoter mutations: Consider testing for these mutations if the discordant pattern persists, as they can affect HBeAg expression without changing viral replication 2

5. Quantitative HBsAg: If available, this test can provide additional information about the viral reservoir and prognosis 4

Pitfalls to Avoid

1. Don't rush to treatment: Starting antiviral therapy in a patient with undetectable HBV DNA and normal LFTs is not supported by guidelines unless there's evidence of advanced fibrosis/cirrhosis 2

2. Don't ignore the HBeAg positivity: Despite undetectable DNA, the positive HBeAg indicates ongoing viral activity and warrants close monitoring 2

3. Don't assume laboratory error: While this pattern is unusual, confirm results before dismissing them as laboratory error

4. Don't extend monitoring intervals too quickly: This unusual pattern requires close initial monitoring before extending to longer intervals 1