What is the difference between antibody to hepatitis B surface antigen (anti‑HBs) and total antibody to hepatitis B core antigen (anti‑HBc), and how are the serologic patterns interpreted?

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Last updated: February 16, 2026 • View editorial policy

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Difference Between Anti-HBs and Anti-HBc

Anti-HBs (antibody to hepatitis B surface antigen) indicates immunity—either from vaccination or recovery from infection—while anti-HBc (antibody to hepatitis B core antigen) indicates exposure to the virus and distinguishes natural infection from vaccine-induced immunity. 1

Anti-HBs: The Immunity Marker

  • Anti-HBs is the protective antibody that develops after successful vaccination or recovery from hepatitis B infection, with levels ≥10 mIU/mL considered protective against HBV infection. 1, 2

  • Anti-HBs appears after HBsAg clearance in natural infection and is the only marker present after vaccination (without anti-HBc). 3, 1

  • This antibody provides long-term protection through immune memory that persists for 30 years or more, even when antibody levels decline below detectable thresholds in immunocompetent individuals. 2

Anti-HBc: The Exposure Marker

  • Anti-HBc (total) appears at the onset of symptoms in acute infection and persists for life in most infected persons, serving as a permanent marker of HBV exposure. 3, 1

  • Anti-HBc is never produced by vaccination—its presence always indicates natural infection (past or present). 3, 1

  • The marker exists in two forms: IgM anti-HBc indicates acute or recent infection (detectable for up to 6 months), while total anti-HBc (IgG + IgM) persists lifelong after infection. 1, 4

Critical Serologic Patterns for Clinical Interpretation

Vaccine-Induced Immunity

  • Anti-HBs positive + Anti-HBc negative + HBsAg negative = immunity from vaccination only. 3, 1

Natural Immunity (Resolved Infection)

  • Anti-HBs positive + Anti-HBc positive + HBsAg negative = recovery from past infection with natural immunity. 3, 1
  • This pattern definitively distinguishes natural immunity from vaccine-derived immunity. 1

Chronic Infection

  • HBsAg positive + Anti-HBc positive (IgG) + Anti-HBs negative = chronic hepatitis B infection. 3, 1
  • Patients with chronic infection have detectable total anti-HBc but usually not IgM anti-HBc, which distinguishes them from acute infection. 3

Acute Infection

  • HBsAg positive + IgM anti-HBc positive + Anti-HBs negative = acute hepatitis B infection. 1, 4

Never Infected/Susceptible

  • All markers negative (HBsAg negative, anti-HBs negative, anti-HBc negative) = never infected and susceptible to HBV. 1

Important Clinical Pitfalls

  • Isolated anti-HBc positivity (anti-HBc positive with negative HBsAg and anti-HBs) most commonly indicates resolved infection with waning anti-HBs levels, but can also represent occult chronic infection, especially in immunocompromised patients. 3, 1

  • In cases of isolated anti-HBc, HBV DNA testing is essential to detect occult hepatitis B, particularly in immunocompromised individuals or those from high-prevalence regions. 3, 1

  • Patients with chronic HBV exacerbations can test positive for IgM anti-HBc, potentially leading to misdiagnosis as acute infection rather than chronic infection with flare. 1

  • IgM anti-HBc should only be used for diagnosis of acute hepatitis B in persons with clinical evidence of acute hepatitis or epidemiologic link to a case, as false positives can occur in asymptomatic persons. 1, 4

  • Anti-HBs levels can decline over time after natural infection, leaving only anti-HBc detectable; this still reflects past infection with residual immunity through immune memory. 1, 2

References

1
Guideline

Hepatitis B Serology Interpretation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Hepatitis B Immunity Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Guideline

Acute Hepatitis B Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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