What is the best Hepatitis B (HBV) screening strategy for a general population without specific risk factors?

Best Hepatitis B Screening Strategy for General Population

For the general population without specific risk factors, universal screening of all adults aged ≥18 years at least once in their lifetime is now the recommended approach, using a three-test panel: HBsAg, anti-HBc, and anti-HBs. 1, 2

Rationale for Universal Screening

The shift from risk-based to universal screening is supported by compelling evidence:

• Risk-based screening misses significant infections: 21% of patients with chronic HBV had no identifiable risk factors in a large prospective study 1
• Risk assessment is impractical: Approximately 90% of patients have at least one risk variable, making selective screening inefficient and requiring nearly universal testing anyway 1
• Low screening rates with risk-based approaches: Oncologists and primary care providers often lack time or familiarity with HBV risk factors, resulting in missed diagnoses 1

Recommended Screening Panel

Three-Test Approach (Preferred)

Order all three tests simultaneously: 1, 3, 2

1. Hepatitis B surface antigen (HBsAg) - detects active infection (acute or chronic) 1
2. Hepatitis B core antibody (anti-HBc) total or IgG - indicates previous or ongoing infection 1, 3, 2
3. Hepatitis B surface antibody (anti-HBs) - indicates immunity from vaccination or resolved infection 3, 2

Interpretation Algorithm

HBsAg	anti-HBc	anti-HBs	Interpretation	Next Steps
Positive	Positive	Negative	Active chronic HBV infection	Order HBeAg, anti-HBe, quantitative HBV DNA; refer to hepatology [3,2]
Negative	Positive	Positive	Resolved infection	No immediate action; consider HBV DNA if immunosuppression planned [3,2]
Negative	Positive	Negative	Isolated core antibody (possible occult HBV)	Order quantitative HBV DNA, especially if immunosuppression planned [3,4]
Negative	Negative	Positive	Immunity from vaccination	No action needed [3,2]
Negative	Negative	Negative	Susceptible to HBV	Offer vaccination [3,2]

Special Populations Requiring Screening

Even with universal screening recommendations, these groups warrant particular attention: 1, 2

High-Priority Groups

• Geographic origin: Persons from countries with HBsAg prevalence ≥2% (Asia, sub-Saharan Africa, Pacific Islands, parts of South America, Eastern Europe) 1
• Behavioral risks: Injection drug users, men who have sex with men, persons with multiple sexual partners 1
• Medical risks: HIV-positive persons, household/sexual contacts of HBV-infected persons, persons on hemodialysis 1
• Immunosuppression planned: Anyone starting chemotherapy, immunosuppressive therapy, or biologic agents 1

Critical Timing for Immunosuppression

For patients starting immunosuppressive therapy, screening is mandatory before treatment initiation (though treatment should not be delayed for results): 1

• High-risk immunosuppression (B-cell depleting agents, anti-CD20 therapy, stem cell transplant): Requires antiviral prophylaxis if HBsAg-positive or anti-HBc-positive 1
• Moderate-risk immunosuppression (anthracyclines, anti-TNF therapy, corticosteroids ≥4 weeks): Consider prophylaxis vs. monitoring based on serologic status 1
• Low-risk immunosuppression (short-term corticosteroids <1 week): Monitoring alone typically sufficient 1

Common Pitfalls to Avoid

Testing Errors

• Do NOT order only HBsAg: This misses resolved infections (anti-HBc-positive) that can reactivate with immunosuppression 1, 3
• Do NOT order IgM anti-HBc for routine screening: This is only for suspected acute hepatitis B 3
• Do NOT skip testing in vaccinated individuals: Breakthrough infections occur, and vaccination history is often unreliable 3, 2

Interpretation Errors

• Isolated anti-HBc positivity (HBsAg-negative, anti-HBc-positive, anti-HBs-negative) represents either distant resolved infection or occult HBV infection 3, 4
  • Occult HBV (detectable HBV DNA despite negative HBsAg) occurs in 2-10% of anti-HBc-positive patients 4
  • Always order HBV DNA testing in these patients if immunosuppression is planned 1, 3

Follow-up Errors

• Low-positive results for anti-HBs or anti-HBc alone are often nonspecific and should be interpreted cautiously 5
• Confirmatory testing with neutralizing assays should be performed for initially reactive HBsAg results 1

Cost-Effectiveness Considerations

While the three-test panel adds cost compared to HBsAg alone, the universal screening approach is justified because: 1

• Risk-based screening requires nearly universal testing anyway (90% of patients have ≥1 risk factor) 1
• Missing occult infections leads to preventable HBV reactivation, hepatic decompensation, and death 1
• Early identification enables HCC surveillance in chronic carriers, improving mortality 6, 7
• Identifying susceptible individuals allows vaccination to prevent future infection 2, 8

Implementation Strategy

Screen all adults ≥18 years at least once with the three-test panel (HBsAg, anti-HBc, anti-HBs) 1, 2

For ongoing risk factors (current injection drug use, multiple sexual partners, healthcare workers with exposure risk), repeat screening periodically 2

Before any immunosuppressive therapy, ensure screening is complete regardless of prior testing, as this is a critical intervention point to prevent morbidity and mortality 1