Laboratory Tests for Hepatitis B Diagnosis and Management
The essential laboratory tests for Hepatitis B diagnosis and management include HBsAg, anti-HBc (total and IgM), anti-HBs, HBeAg, anti-HBe, HBV DNA quantification, and liver function tests. 1
Initial Diagnostic Testing
Core Serological Panel
- HBsAg (Hepatitis B Surface Antigen): Primary marker of active HBV infection
- Anti-HBc (Hepatitis B Core Antibody):
- Total anti-HBc: Indicates previous or ongoing HBV infection
- IgM anti-HBc: Indicates acute or recent infection (within 6 months)
- Anti-HBs (Hepatitis B Surface Antibody): Indicates recovery from infection or successful vaccination
This panel distinguishes between:
- Acute infection: HBsAg positive, IgM anti-HBc positive
- Chronic infection: HBsAg positive for >6 months, IgM anti-HBc negative, total anti-HBc positive
- Past infection with immunity: HBsAg negative, anti-HBs positive, total anti-HBc positive
- Vaccine-induced immunity: HBsAg negative, anti-HBs positive, total anti-HBc negative 1
Additional Serological Markers
- HBeAg (Hepatitis B e Antigen): Marker of high viral replication
- Anti-HBe (Antibody to HBeAg): Generally indicates lower viral replication 1
Viral Replication Assessment
- HBV DNA quantification: Critical for:
- Confirming diagnosis (detectable HBV DNA is a criterion for chronic HBV)
- Determining disease phase and activity
- Treatment decisions
- Monitoring response to therapy 1
HBV DNA thresholds:
- HBeAg-positive CHB: ≥20,000 IU/mL indicates active viral replication
- HBeAg-negative CHB: ≥2,000 IU/mL differentiates from inactive carrier state 1
Liver Function Tests
- ALT/AST: Assess liver inflammation and disease activity
- Alkaline phosphatase, gamma-glutamyl transpeptidase: Additional markers of liver function
- Bilirubin, albumin, prothrombin time: Assess liver synthetic function 1, 2
Additional Testing for Complete Evaluation
- Complete blood count: Baseline assessment
- Tests for coinfection: Anti-HCV, anti-HDV, anti-HIV (in high-risk individuals)
- Hepatitis A immunity (IgG anti-HAV): To determine need for HAV vaccination 1
Special Circumstances
Occult HBV Infection
For patients with isolated anti-HBc positivity (HBsAg negative, anti-HBs negative):
- HBV DNA testing is recommended to detect occult HBV infection
- Important in:
- Cryptogenic liver disease
- Prior to immunosuppressive therapy
- Solid organ transplant donors 1
Window Period
During the "window period" when HBsAg disappears and anti-HBs is not yet detectable:
- IgM anti-HBc is the only marker of infection
- Follow-up testing in 3-6 months is recommended 1
Monitoring During Treatment
For patients on antiviral therapy:
- HBV DNA levels: Every 3-6 months to assess virologic response
- ALT/AST: Every 3 months initially, then every 3-6 months
- HBeAg/anti-HBe: Every 6 months in HBeAg-positive patients
- HBsAg quantification: Consider in selected patients to predict response 2
Pitfalls and Caveats
Isolated anti-HBc can represent:
- Window period of acute infection
- Remote resolved infection with waned anti-HBs
- Occult HBV infection
- False-positive result 1
HBV DNA levels may fluctuate in HBeAg-negative CHB, requiring serial testing to distinguish from inactive carrier state 1
Low-level viremia (<2,000 IU/mL) does not exclude significant liver disease; some patients with cirrhosis may have low viral loads 1
Patients with normal ALT may still have significant liver disease, particularly in HBeAg-negative CHB 1, 2
By following this comprehensive testing approach, clinicians can accurately diagnose HBV infection, determine disease phase, make appropriate treatment decisions, and monitor response to therapy, ultimately reducing morbidity and mortality from chronic HBV infection.