What is the recommended screening test for individuals at risk of hepatitis B (HB) infection, particularly those with a history of high-risk behaviors or from endemic areas?

Hepatitis B Surface Antigen Screening

Hepatitis B surface antigen (HBsAg) is the recommended primary screening test for detecting active hepatitis B infection, and should be performed using FDA-approved tests followed by confirmatory testing for initially reactive results. 1

Recommended Screening Panel

The optimal approach uses a comprehensive three-test panel rather than HBsAg alone:

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

This three-test panel is now recommended for universal screening of all adults aged ≥18 years at least once in their lifetime, as risk-based screening misses 21% of chronic HBV infections in patients with no identifiable risk factors. 3, 4

Who Should Be Screened

Universal Screening

• All adults aged ≥18 years should be screened at least once 2, 4

High-Priority Risk Groups (≥2% HBV prevalence)

• Persons born in Asia, Africa, Pacific Islands, parts of South America, or Eastern Europe 1
• U.S.-born persons not vaccinated as infants whose parents were born in regions with ≥8% HBsAg prevalence 1
• Persons with HIV infection 1
• Current or past injection drug users 1
• Men who have sex with men 1
• Household contacts or sexual partners of HBsAg-positive persons 1
• Persons with hepatitis C virus infection 5
• Persons requiring immunosuppressive therapy 1, 5
• Persons incarcerated or formerly incarcerated 4
• Persons with history of sexually transmitted infections 4

Critical Timing Considerations

Before immunosuppressive therapy, screening is mandatory - this represents a critical intervention point to prevent HBV reactivation, hepatic decompensation, and death. 1, 3 Testing should include at minimum HBsAg and anti-HBc, as both HBsAg-positive and isolated anti-HBc-positive patients require antiviral prophylaxis when receiving high-risk immunosuppression. 1

Test Interpretation Algorithm

HBsAg	Anti-HBc	Anti-HBs	Interpretation
Positive	Positive	Negative	Active HBV infection (chronic or acute) - requires HBV DNA testing and specialist referral [2,3]
Negative	Positive	Positive	Resolved infection with immunity [3]
Negative	Positive	Negative	Isolated core antibody - possible occult HBV, requires HBV DNA testing [3]
Negative	Negative	Positive	Immunity from vaccination [2,3]
Negative	Negative	Negative	Susceptible to HBV - needs vaccination [2,3]

Follow-Up Testing for Positive Results

When HBsAg is positive, order additional tests:

• HBV DNA (quantitative) - essential for assessing viral replication and treatment decisions 1, 3
• HBeAg and anti-HBe - indicates level of viral replication 3
• Alanine aminotransferase (ALT) - assesses liver inflammation 1

Screening Intervals

Periodic rescreening is recommended for persons with ongoing risk factors, including:

• Current injection drug users - screen periodically 1
• Men who have sex with men with multiple partners - screen periodically 1
• Persons on hemodialysis - screen annually 5

Common Pitfalls to Avoid

• Do not order HBsAg alone - this misses past infections and occult HBV that require monitoring before immunosuppression 3
• Do not skip screening based on vaccination history - breakthrough infections can occur and testing is still indicated 1, 3
• Do not order IgM anti-HBc for routine screening - this is only for suspected acute hepatitis B 3
• Do not delay cancer or immunosuppressive therapy while awaiting results - testing should be done proactively, but treatment should not be postponed 3
• Always use FDA-approved HBsAg tests with confirmatory testing for reactive results - this prevents false-positive diagnoses 1