What are hepatitis B surface antibody (anti‑HBs), hepatitis B core antibody IgM (anti‑HBc IgM), and hepatitis B core antibody IgG (anti‑HBc IgG)?

Understanding Hepatitis B Serological Markers

Anti-HBs (Hepatitis B Surface Antibody)

Anti-HBs is the antibody that develops after either successful hepatitis B vaccination or recovery from natural HBV infection, and it provides protective immunity against future hepatitis B infection. 1

• Anti-HBs appears after clearance of HBsAg (hepatitis B surface antigen) in natural infection and is the sole marker present after vaccination, indicating protective immunity 2
• A level of ≥10 mIU/mL is considered protective and confirms immunity 1, 2
• When anti-HBs is the only positive marker, this confirms immunity from vaccination alone without prior natural infection 1
• When anti-HBs is positive alongside anti-HBc (and HBsAg negative), this indicates recovery from past natural infection with resulting immunity 1, 2

Anti-HBc IgM (Hepatitis B Core Antibody IgM)

Anti-HBc IgM is the definitive marker for acute or recently acquired hepatitis B infection, appearing at symptom onset and typically persisting for up to 6 months after infection. 3

• IgM anti-HBc is the most reliable marker for distinguishing acute from chronic HBV infection 3
• It appears at the onset of symptoms or liver test abnormalities in acute HBV infection 3
• A strong positive IgM anti-HBc during acute hepatitis is indicative of acute HBV infection even in HBsAg-negative patients 4
• Testing should be limited to persons with clinical evidence of acute hepatitis or epidemiologic link to HBV infection due to low positive predictive value in asymptomatic persons 3

Important Clinical Caveat

• In patients with chronic HBV infection, IgM anti-HBc can persist at low levels during viral replication or during exacerbations, potentially leading to misdiagnosis as acute infection 3, 4
• Weak positive results in HBsAg-positive patients without recent acute hepatitis cannot always be regarded as definite markers of recent infection 4

Anti-HBc IgG (Total Anti-HBc)

Total anti-HBc (which includes both IgM and IgG) appears at symptom onset and persists for life in most infected persons, serving as a permanent marker of HBV exposure—past or present. 2

• Total anti-HBc remains detectable for life after hepatitis B infection 2
• Anti-HBc is never generated by vaccination; its presence always signifies natural infection (past or present) 2
• This marker is the key differentiator between natural immunity (anti-HBc positive + anti-HBs positive) and vaccine-induced immunity (anti-HBc negative + anti-HBs positive) 1, 2

Clinical Interpretation Algorithm

For determining immune status:

1. First-line testing: Measure HBsAg and anti-HBs simultaneously to identify current infection and immunity 1
2. If anti-HBs is positive: Add total anti-HBc to distinguish natural immunity (anti-HBc positive) from vaccine-induced immunity (anti-HBc negative) 1

For diagnosing acute vs. chronic infection:

• Acute infection: HBsAg positive + IgM anti-HBc positive + Anti-HBs negative 3
• Chronic infection: HBsAg positive + IgM anti-HBc negative (but total anti-HBc positive) + Anti-HBs negative 3
• Resolved infection: HBsAg negative + Anti-HBs positive + Total anti-HBc positive 2, 3
• Vaccine immunity only: HBsAg negative + Anti-HBs positive + Anti-HBc negative 2

Special consideration for isolated anti-HBc positivity:

• Resolved infection with waning anti-HBs is the most common explanation in high-prevalence populations 2
• Consider HBV DNA testing to detect occult hepatitis B, especially in immunocompromised individuals or those from high-prevalence regions 2