How is Hepatitis B (HBV) serology interpreted?

Hepatitis B Serology Interpretation

Hepatitis B serology interpretation requires analysis of specific viral markers (HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe, and HBV DNA) to determine infection status, which can be categorized as never infected, acute infection, chronic infection, resolved infection, or vaccine-induced immunity. 1

Key Serological Markers and Their Significance

Primary Diagnostic Markers

• HBsAg (Hepatitis B Surface Antigen): First serological marker to appear in acute infection (30 days average after exposure, range 6-60 days); persistence for >6 months indicates chronic infection 1
• Anti-HBc (Antibody to Hepatitis B Core Antigen): Appears at onset of symptoms; total anti-HBc persists for life in most infected persons 1
• IgM anti-HBc: Indicates acute or recently acquired infection; typically detectable for up to 6 months after infection 1
• Anti-HBs (Antibody to Hepatitis B Surface Antigen): Indicates recovery from infection or successful vaccination; marker of immunity 1

Additional Markers

• HBeAg (Hepatitis B e Antigen): Indicates high viral replication and infectivity 1
• Anti-HBe (Antibody to HBeAg): Usually indicates decreased viral replication 1
• HBV DNA: Direct measure of viral replication; essential for characterizing infection status, diagnosis, treatment decisions, and monitoring 1

Interpretation of Serologic Patterns

Never Infected

• HBsAg negative
• Anti-HBc negative
• Anti-HBs negative 1

Acute Infection

• HBsAg positive
• IgM anti-HBc positive
• Anti-HBs negative
• HBV DNA positive 1

Chronic Infection

• HBsAg positive (persists >6 months)
• Total anti-HBc positive
• IgM anti-HBc negative
• Anti-HBs negative
• HBV DNA typically positive 1

Natural Immunity (Resolved Infection)

• HBsAg negative
• Total anti-HBc positive
• Anti-HBs positive
• HBV DNA negative 1

Vaccine-Induced Immunity

• HBsAg negative
• Anti-HBc negative
• Anti-HBs positive (≥10 mIU/mL indicates protection)
• HBV DNA negative 1

Isolated Anti-HBc

• HBsAg negative
• Total anti-HBc positive
• Anti-HBs negative
• May represent:
  • False-positive result
  • Past infection with waning anti-HBs
  • "Low-level" chronic infection
  • Occult HBV infection 1

Phases of Chronic HBV Infection

Chronic HBV infection can be categorized into three main phases:

1. Immune Tolerant Phase:

   • HBeAg positive
   • High HBV DNA levels
   • Normal liver enzymes
   • Minimal liver inflammation 1

2. Immune Active/Chronic Hepatitis Phase:

   • HBeAg positive or negative
   • High HBV DNA levels
   • Elevated liver enzymes
   • Active liver inflammation 1

3. Inactive Phase:

   • HBeAg negative
   • Anti-HBe positive
   • Low or undetectable HBV DNA (<2,000 IU/mL)
   • Normal liver enzymes 1

Clinical Pearls and Pitfalls

• Transient HBsAg positivity can occur for up to 18 days after hepatitis B vaccination and is clinically insignificant 1

• IgM anti-HBc should be used for diagnosis of acute hepatitis B only in persons with clinical evidence of acute hepatitis or epidemiologic link to a case, as false positives can occur 1

• Occult HBV infection is characterized by undetectable HBsAg but detectable HBV DNA in serum or liver tissue 1, 2

• HBV reactivation can occur in persons with resolved infection who become immunosuppressed (e.g., from chemotherapy, immunosuppressive medications) 1

• Highly sensitive nucleic acid tests can detect HBV DNA 10-20 days before HBsAg appears 1

• Patients with exacerbations of chronic infection can test positive for IgM anti-HBc, potentially leading to misdiagnosis as acute infection 1, 3