What do the different hepatitis B (HBV) serology markers, such as HBsAg (hepatitis B surface antigen), HBsAb (hepatitis B surface antibody), HBeAg (hepatitis B e-antigen), HBeAb (hepatitis B e-antibody), and HBcAb (hepatitis B core antibody), indicate?

Hepatitis B Serology Markers and Their Clinical Interpretation

Understanding hepatitis B serology markers is essential for accurate diagnosis, treatment decisions, and monitoring of disease progression, as these markers directly impact mortality and morbidity outcomes in patients with HBV infection.

Key Hepatitis B Serology Markers

1. Hepatitis B Surface Antigen (HBsAg)

• Significance: Indicates active HBV infection (acute or chronic)
• Timing: First marker to appear, detectable 30 days after exposure (range: 6-60 days) 1
• Interpretation:
  • Presence for >6 months indicates chronic infection
  • Disappearance indicates recovery from infection
  • Can be transiently positive for up to 18 days after vaccination (clinically insignificant) 1

2. Hepatitis B Surface Antibody (anti-HBs)

• Significance: Indicates immunity to HBV
• Timing: Appears during convalescence, typically 3-4 months after infection resolves 1
• Interpretation:
  • Presence alone (without anti-HBc) indicates immunity from vaccination
  • Presence with anti-HBc indicates immunity from resolved natural infection
  • Provides protection against all HBV genotypes 1

3. Hepatitis B Core Antibody (anti-HBc)

• Types: Total anti-HBc and IgM anti-HBc
• Significance: Indicates exposure to HBV
• Timing: Appears at onset of symptoms and persists for life 1
• Interpretation:
  • IgM anti-HBc: Indicates acute or recent infection (present for up to 6 months)
  • Total anti-HBc without HBsAg: Indicates resolved infection
  • Isolated anti-HBc (without HBsAg or anti-HBs): May indicate:
    • Resolved infection with waned anti-HBs
    • False-positive result
    • "Window period" during acute infection
    • Occult HBV infection 1

4. Hepatitis B e Antigen (HBeAg)

• Significance: Marker of viral replication and infectivity
• Interpretation:
  • Presence indicates high viral replication and high infectivity
  • Useful for monitoring chronic infection and treatment response
  • Presence with high HBV DNA levels indicates active viral replication 1

5. Hepatitis B e Antibody (anti-HBe)

• Significance: Indicates decreased viral replication
• Interpretation:
  • Appearance usually indicates transition to inactive carrier state
  • Associated with lower HBV DNA levels and reduced infectivity
  • Can be present in HBeAg-negative chronic hepatitis B with precore/core promoter mutations 1

6. HBV DNA

• Significance: Direct measure of viral load
• Timing: Can be detected 10-20 days before HBsAg appears 1
• Interpretation:
  • High levels indicate active viral replication
  • Used to monitor treatment response
  • Essential for diagnosing occult HBV infection (HBsAg-negative but HBV DNA-positive) 2

Clinical Interpretation of Serologic Patterns

1. Acute HBV Infection

• Serologic pattern: HBsAg (+), IgM anti-HBc (+), HBeAg (+), anti-HBs (-), anti-HBe (-)
• Clinical significance: Active infection with high viral replication
• Monitoring: Follow for resolution or progression to chronic infection 3

2. Resolved HBV Infection with Immunity

• Serologic pattern: HBsAg (-), Total anti-HBc (+), IgM anti-HBc (-), anti-HBs (+)
• Clinical significance: Past infection with immunity
• Monitoring: No specific monitoring needed unless immunosuppression is planned 3

3. Chronic HBV Infection

• Serologic pattern: HBsAg (+), Total anti-HBc (+), IgM anti-HBc (-), anti-HBs (-)
• Clinical significance: Ongoing infection with risk of liver disease progression
• Phases:
  • Immune tolerant: HBeAg (+), high HBV DNA, normal ALT, minimal liver disease
  • Immune active: HBeAg (+), high HBV DNA, elevated ALT, active liver inflammation
  • Inactive carrier: HBeAg (-), anti-HBe (+), low/undetectable HBV DNA, normal ALT
  • Reactivation phase: HBeAg (-), anti-HBe (+), elevated HBV DNA, elevated ALT 1

4. Vaccination-Induced Immunity

• Serologic pattern: HBsAg (-), Total anti-HBc (-), anti-HBs (+)
• Clinical significance: Immunity from vaccination
• Monitoring: No specific monitoring needed 3

5. Occult HBV Infection

• Serologic pattern: HBsAg (-), HBV DNA (+), variable other markers
• Clinical significance: Risk of reactivation during immunosuppression, potential for transmission, risk of HCC
• Monitoring: Important to identify before immunosuppressive therapy 4

Clinical Pitfalls and Caveats

1. IgM anti-HBc testing: Should be limited to persons with clinical evidence of acute hepatitis or epidemiologic link to a case, as false positives can occur in asymptomatic persons 1

2. Reactivation risk: Patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive) can experience reactivation during immunosuppression, particularly with anti-CD20 therapies 3

3. Isolated anti-HBc: Requires careful interpretation and may warrant HBV DNA testing to rule out occult infection 1

4. HBeAg-negative chronic hepatitis: Can occur with precore/core promoter mutations, resulting in active disease despite negative HBeAg 1

5. Unusual serologic patterns: Rare cases with all markers positive can occur and require careful interpretation 5

6. Transient HBsAg after vaccination: Can be positive for up to 18 days after vaccination but is clinically insignificant 1

Understanding these serologic markers is crucial for appropriate patient management, as chronic HBV infection is associated with significant mortality, with approximately 25% of those infected as children and 15% of those infected as adults dying from cirrhosis or hepatocellular carcinoma 1.