Given hepatitis B surface antigen positive, antibody to hepatitis B e antigen positive, and hepatitis B core IgG antibody positive, what does this serology indicate and what is the recommended next step in management?

Hepatitis B Serology Interpretation: HBsAg Positive, Anti-HBe Positive, Anti-HBc IgG Positive

This serological pattern indicates chronic hepatitis B infection with seroconversion from HBeAg to anti-HBe, and you must immediately obtain HBV DNA quantification and ALT levels to distinguish between the favorable inactive carrier state and the potentially aggressive HBeAg-negative chronic hepatitis B. 1

What This Serology Tells You

Your patient has chronic HBV infection (HBsAg positive for >6 months) with evidence of past or ongoing infection (anti-HBc IgG positive) and has undergone seroconversion from HBeAg to anti-HBe positivity. 2, 1 This anti-HBe positivity typically indicates decreased viral replication, but this is not absolute—you cannot assume this patient is an inactive carrier without further testing. 1, 3

The presence of anti-HBc IgG (not IgM) confirms this is chronic infection rather than acute infection. 1 IgM anti-HBc would indicate acute infection, but its absence here rules that out. 2, 4

Critical Next Steps: The Diagnostic Algorithm

Step 1: Obtain HBV DNA quantification immediately 1, 3

• This is the single most important test to determine disease activity
• HBV DNA <2,000 IU/mL suggests inactive carrier state 1, 3
• HBV DNA ≥2,000 IU/mL indicates HBeAg-negative chronic hepatitis B 1, 3

Step 2: Measure ALT/AST levels 1, 3

• Normal ALT supports inactive carrier diagnosis 1
• Elevated or fluctuating ALT indicates active hepatitis 1

Step 3: Monitor ALT every 3-4 months for at least one year 1

• ALT can fluctuate, particularly in HBeAg-negative disease 1
• A single normal ALT is insufficient to confirm inactive carrier status 1

Two Completely Different Clinical Scenarios

Scenario A: Inactive Carrier State (Favorable Prognosis)

Criteria: HBV DNA <2,000 IU/mL + persistently normal ALT 1, 3

• Very favorable long-term prognosis with minimal risk of cirrhosis or HCC 1
• Minimal liver inflammation and fibrosis 1
• Management: Monitor ALT every 6 months for life and measure HBV DNA every 6 months to detect reactivation 1
• Approximately 20% will reactivate to HBeAg-negative chronic hepatitis B, requiring lifelong surveillance 1

Scenario B: HBeAg-Negative Chronic Hepatitis B (High-Risk Disease)

Criteria: HBV DNA ≥2,000 IU/mL + elevated ALT 1, 3

• Severe liver necroinflammation with high risk of cirrhosis, decompensated cirrhosis, and HCC 1, 3
• Low rates of spontaneous remission 1
• Caused by HBV mutants that no longer produce HBeAg 1
• Management: Antiviral therapy is recommended if HBV DNA ≥2,000 IU/mL with elevated ALT 1

Critical Pitfalls to Avoid

Never assume anti-HBe positivity means inactive disease. HBeAg-negative chronic hepatitis B patients can have moderate to high HBV DNA levels despite being anti-HBe positive. 1, 3 This is a distinct and aggressive disease entity with worse outcomes than HBeAg-positive disease. 1

Never rely on a single ALT or HBV DNA measurement. Levels fluctuate, particularly in HBeAg-negative disease, and you need serial measurements over at least one year to confirm inactive carrier status. 1

Do not confuse this with resolved infection. Resolved infection would show HBsAg negative, anti-HBs positive, and anti-HBc positive. 1 Your patient is HBsAg positive, indicating ongoing chronic infection. 2, 5

Why HBV DNA and ALT Are Non-Negotiable

Without HBV DNA quantification, you cannot distinguish between a patient with excellent prognosis (inactive carrier, 10-year HCC risk 1.7%) versus a patient with severe disease requiring antiviral therapy (HBeAg-negative chronic hepatitis B). 1 The presence of anti-HBe alone does not predict viral load or disease activity. 1, 3

The anti-HBe seroconversion your patient has undergone is a natural transition during chronic HBV infection, but it does not guarantee disease resolution or inactivity. 1, 6 Approximately 10-40% of patients who achieve HBeAg seroconversion will revert to HBeAg positivity, particularly with HBV genotype C. 1

Infectivity Considerations

While anti-HBe positivity generally correlates with lower infectivity compared to HBeAg-positive patients, your patient remains infectious if HBV DNA is detectable. 2, 5 HBV DNA is the direct measure of viral replication and infectivity. 2