Serologic Tests for Past Hepatitis A and B Infection
Tests for Past Hepatitis A Infection
IgG anti-HAV (total anti-HAV) is the definitive test to confirm past hepatitis A infection and indicates lifelong immunity. 1
- IgG anti-HAV appears during the early phase of acute infection and persists indefinitely after recovery, providing a permanent marker of prior HAV exposure 2
- This antibody indicates complete immunity from future hepatitis A infections 2
- The test cannot distinguish between vaccine-induced immunity and natural infection-acquired immunity, as both produce positive IgG anti-HAV 3
- Important caveat: If differentiation between vaccination and natural infection is clinically necessary (such as for outbreak investigations or vaccination campaign evaluations), HAV non-structural protein 2A testing can distinguish these two scenarios with 92% accuracy, though this is not routinely available 4
Tests for Past Hepatitis B Infection
The combination of positive anti-HBc (total) and positive anti-HBs with negative HBsAg definitively confirms resolved past hepatitis B infection with natural immunity. 1, 5
Essential Serologic Pattern for Past HBV Infection:
- Anti-HBc (total): Must be positive and persists for life after HBV infection 1
- Anti-HBs: Must be positive (≥10 mIU/mL indicates protective immunity) 1, 5
- HBsAg: Must be negative (confirms viral clearance) 1
- HBV DNA: Should be negative or undetectable 5
Critical Distinction from Vaccine-Induced Immunity:
Anti-HBc is the key differentiating marker: Persons who recover from natural HBV infection are positive for both anti-HBs AND anti-HBc, whereas persons who respond to hepatitis B vaccine are positive only for anti-HBs and negative for anti-HBc 1, 6
Recommended Testing Algorithm:
The most efficient and cost-effective screening approach for determining HBV immune status involves: 3
First-line testing: HBsAg and anti-HBs
Second-line testing (if anti-HBs positive): Anti-HBc (total)
Important Clinical Pitfalls:
Isolated anti-HBc positivity (positive anti-HBc with negative HBsAg and negative anti-HBs) can represent: 1
- Resolved infection with waning anti-HBs levels (most common in high-prevalence populations)
- Occult chronic infection with undetectable HBsAg (HBV DNA detectable in <5% of cases)
- False-positive reaction (more common in low-prevalence populations)
In patients with isolated anti-HBc, HBV DNA testing may be helpful to detect occult hepatitis B, particularly in immunocompromised patients or those from high-prevalence populations 1
Anti-HBs levels can wane over time after natural infection, leaving only anti-HBc detectable, but this still represents past infection with residual immunity 1
Approximately 5% of patients who recover from natural HBV infection do not develop detectable anti-HBs despite viral clearance 7