Understanding Anti-HBe Laboratory Reporting
Anti-HBe is not reported as "less than 1 is positive"—this appears to be a misunderstanding of how the test is interpreted. Anti-HBe is typically reported qualitatively as either "positive" (detected) or "negative" (not detected), or quantitatively with specific cutoff values that vary by assay platform 1.
How Anti-HBe Testing Actually Works
The interpretation depends entirely on the specific assay manufacturer's cutoff values, not a universal "less than 1" threshold. Different laboratory platforms use different methodologies (enzyme immunoassay, chemiluminescence, etc.) with manufacturer-specific cutoff indices 1.
Standard Reporting Methods
- Qualitative results: Simply reported as "positive" or "negative" based on whether antibody is detected above the assay's threshold 1
- Semi-quantitative results: May report an index value or signal-to-cutoff ratio, where values above the manufacturer's specified cutoff (often >1.0, not <1.0) indicate positivity 1
- The cutoff is assay-specific: Each manufacturer establishes their own threshold during validation, and this must be clearly stated in the laboratory report 1
Clinical Significance of Anti-HBe
Anti-HBe positivity indicates seroconversion from HBeAg and usually signals decreased viral replication, but clinical interpretation requires the complete serologic profile. 1
Key Clinical Contexts
Inactive carrier state: HBsAg positive, HBeAg negative, anti-HBe positive, HBV DNA <2,000 IU/mL, persistently normal ALT—this represents a favorable prognosis with minimal liver inflammation 1
HBeAg-negative chronic hepatitis B: HBsAg positive, HBeAg negative, anti-HBe positive, HBV DNA ≥2,000 IU/mL, elevated ALT—this is a severe disease entity associated with precore/core promoter mutants, high risk of cirrhosis and hepatocellular carcinoma 1
Resolved infection: HBsAg negative, anti-HBe positive, anti-HBc positive—indicates past infection with natural immunity 1
Critical Pitfall to Avoid
Never assume anti-HBe positivity alone indicates low disease activity or favorable prognosis. You must simultaneously measure HBV DNA and ALT levels, as approximately 15-40% of anti-HBe positive patients have HBeAg-negative chronic hepatitis B with ongoing high-level viral replication and severe liver inflammation 1, 2. These patients have poor outcomes with 54% developing cirrhosis during follow-up 2.
Essential Concurrent Testing
- Always measure HBV DNA quantitatively: The threshold of 2,000 IU/mL distinguishes inactive carriers from HBeAg-negative chronic hepatitis B 1
- Monitor ALT levels: Single measurements are insufficient; follow ALT every 3-4 months for at least one year to detect fluctuations characteristic of HBeAg-negative disease 1
- Confirm HBeAg status: Must verify HBeAg negativity, as the HBeAg/anti-HBe system directly determines infection phase and treatment decisions 1, 3
Temporal Dynamics of Anti-HBe
Anti-HBe typically appears 2 weeks after peak ALT in acute hepatitis B and persists for years after recovery. 4 In chronic infection, seroconversion from HBeAg to anti-HBe can occur spontaneously but does not guarantee disease resolution—continued monitoring is mandatory 1, 5.