What is the diagnosis and management plan for a patient with abnormal liver function tests, including Hepatitis B (HBV) surface antigen positive, HBV surface antibody negative, HBV core antibody (cAb) Immunoglobulin G (IgG) positive, and positive Hepatitis B e-antigen (HBeAg), who is asymptomatic and has a history of blood transfusions 10 years ago?

Diagnosis: Chronic HBeAg-Positive Hepatitis B (Not Inactive Carrier State)

This patient has chronic HBeAg-positive hepatitis B infection, not chronic inactive hepatitis, despite normal liver enzymes. The serological pattern—HBsAg positive, anti-HBs negative, anti-HBc IgG positive (with negative IgM), and critically, positive HBeAg—indicates active viral replication and rules out the inactive carrier state 1.

Serological Analysis

The key distinguishing features of this patient's profile:

• HBsAg positive for >6 months (given 10-year history): Confirms chronic infection 1
• Anti-HBc IgG positive, IgM negative: Indicates chronic rather than acute infection 1
• HBeAg positive: This is the critical marker indicating active viral replication and high infectivity 1
• Anti-HBs negative: Rules out resolved infection or immunity 1, 2

Why this is NOT chronic inactive hepatitis: The inactive carrier state requires HBeAg negativity with anti-HBe positivity, HBV DNA <2,000 IU/mL, and persistently normal ALT 1, 2. This patient has positive HBeAg, which automatically excludes the inactive carrier diagnosis regardless of normal transaminases 1.

Critical Next Steps

Immediate Testing Required

1. HBV DNA quantification: Essential to determine viral load and guide treatment decisions 1, 2

   • HBeAg-positive chronic hepatitis typically shows HBV DNA ≥20,000 IU/mL 1
   • This will confirm active replication status

2. Repeat ALT/AST monitoring: Normal enzymes at one timepoint do not exclude chronic active hepatitis 1

   • Monitor every 3-4 months for at least one year to detect fluctuations 2
   • Some patients with HBeAg-positive disease have intermittently normal ALT 1

3. Hepatitis D (HDV) antibody: Given transfusion history, must exclude coinfection 1

4. Hepatitis C (HCV) antibody: Rule out coinfection from prior transfusion 1

5. HIV testing: Should be offered before considering entecavir therapy 3

Liver Disease Assessment

• Abdominal ultrasound and alpha-fetoprotein: Screen for cirrhosis and hepatocellular carcinoma 1
• Consider liver biopsy or non-invasive fibrosis assessment: To determine degree of hepatic necroinflammation and fibrosis, especially if HBV DNA is elevated 1

Management Approach

If HBV DNA ≥20,000 IU/mL:

Antiviral therapy is indicated even with normal ALT if there is evidence of significant liver inflammation on biopsy or non-invasive markers 1. Treatment options include:

• Entecavir 0.5 mg daily (first-line for treatment-naïve patients) 3
• Tenofovir disoproxil fumarate 1
• Peginterferon alfa-2a (finite duration option) 1

If HBV DNA <20,000 IU/mL but detectable:

• Continue monitoring every 3-6 months 1, 2
• Consider biopsy to assess histological activity 1
• Treatment may still be warranted if moderate-to-severe inflammation present 1

Common Pitfalls to Avoid

1. Do not assume normal ALT means inactive disease: HBeAg-positive patients can have normal transaminases during the immune-tolerant phase but still have active viral replication and risk of progression 1, 2

2. Do not delay HBV DNA testing: This is the definitive test to distinguish between phases of chronic HBV infection 1, 2

3. Do not miss the significance of positive HBeAg: This marker indicates high viral replication regardless of other findings 1

4. Do not forget hepatocellular carcinoma surveillance: All chronic HBV patients require lifelong monitoring with ultrasound and AFP every 6 months 1

5. Do not start entecavir without HIV testing: Risk of HIV resistance if undiagnosed HIV coinfection exists 3

Long-term Monitoring

• Lifelong follow-up required even if currently asymptomatic 1
• HCC surveillance every 6 months with ultrasound and AFP 1
• Monitor for HBeAg seroconversion (loss of HBeAg, appearance of anti-HBe) as treatment endpoint 1
• Assess for treatment need based on HBV DNA levels, ALT trends, and fibrosis stage 1

The correct answer is neither B (acute infection—ruled out by negative IgM anti-HBc) nor D (chronic inactive hepatitis—ruled out by positive HBeAg). This represents chronic HBeAg-positive hepatitis B requiring further evaluation and likely treatment 1, 2.