What are the next steps after a positive hepatitis core antibody (Hep Core Ab) test?

Management of Positive Hepatitis B Core Antibody

Immediately order HBsAg, anti-HBs, and HBV DNA to determine whether this represents chronic infection, resolved infection with immunity, or occult hepatitis B. 1, 2

Initial Diagnostic Workup

The positive hepatitis B core antibody (anti-HBc) indicates past or present HBV infection but cannot distinguish between active, chronic, or resolved infection on its own. 2 The following tests must be obtained immediately:

• HBsAg (Hepatitis B surface antigen) - determines active infection 1, 2
• Anti-HBs (Hepatitis B surface antibody) - determines immunity 1, 2
• HBV DNA - quantifies viral replication if HBsAg positive or if immunosuppression is planned 1, 2
• ALT/AST - assesses hepatic inflammation 1

Interpretation Based on Serologic Profile

Scenario 1: HBsAg Positive (Chronic HBV Infection)

Start antiviral therapy immediately with entecavir 0.5 mg daily, tenofovir disoproxil fumarate, or tenofovir alafenamide if HBV DNA ≥2,000 IU/mL and ALT is elevated. 1

• For patients with cirrhosis, treat immediately with any detectable HBV DNA regardless of ALT levels 1
• Avoid lamivudine due to resistance rates up to 70% at 5 years 1
• Long-term therapy is typically required for HBeAg-negative chronic hepatitis B 1
• Monitor HBV DNA every 3 months until undetectable, then every 6 months 1
• Check liver enzymes (ALT/AST) every 3-6 months 1
• Perform ultrasound every 6 months for hepatocellular carcinoma surveillance in high-risk patients (Asian men >40 years, Asian women >50 years, any patient with cirrhosis, family history of HCC, age >40 years with persistently elevated ALT) 1

Scenario 2: HBsAg Negative, Anti-HBs Positive (Resolved Infection with Immunity)

No treatment is necessary as the patient has immunity from resolved past infection. 1, 2

• This represents resolved HBV infection with protective immunity 1, 2
• No further HBV-specific monitoring is required unless the patient will undergo immunosuppression 1, 2

Scenario 3: HBsAg Negative, Anti-HBs Negative (Isolated Anti-HBc)

Measure HBV DNA to distinguish between occult hepatitis B, false-positive anti-HBc, or resolved infection with waning anti-HBs. 1, 2

This pattern requires careful evaluation as it may represent:

• Resolved infection with decreasing anti-HBs levels 1, 2
• False-positive anti-HBc (can occur after IVIG administration with 15% passive transfer rate) 1
• Window period of acute infection 1, 2
• Occult HBV infection 1, 2

If HBV DNA is detectable, this confirms occult hepatitis B and requires close monitoring due to reactivation risk with immunosuppression. 1

Special Management for Patients Requiring Immunosuppression

High-Risk Immunosuppression (Anti-CD20 therapy, Stem Cell Transplant)

For HBsAg-negative, anti-HBc-positive patients receiving anti-CD20 antibodies (e.g., rituximab) or stem cell transplantation, start antiviral prophylaxis immediately. 3, 1

• Use entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide 1
• Continue prophylaxis for at least 12 months after last dose of anti-CD20 therapy 3, 1
• The American College of Rheumatology strongly recommends prophylactic antiviral therapy over monitoring alone for rituximab regardless of HBsAg status 3

Moderate-Risk Immunosuppression (Other Systemic Anticancer Therapy)

For HBsAg-negative, anti-HBc-positive patients receiving other systemic anticancer therapy, the 2025 AGA guideline suggests monitoring alone over prophylaxis for low-risk regimens, but prophylaxis is conditionally recommended for moderate-risk regimens. 3

The alternative approach is close monitoring with:

• HBsAg and ALT every 3 months during therapy 3, 1
• HBV DNA every 1-3 months 3, 1
• Immediate antiviral therapy at earliest sign of reactivation 3, 1
• Continue monitoring until 12 months after cessation of immunosuppressive therapy 1

If HBsAg becomes positive or HBV DNA becomes detectable during monitoring, start antiviral therapy immediately. 3, 1

Cancer Patients

All cancer patients anticipating systemic anticancer therapy must be tested for HBV using HBsAg, total anti-HBc, and anti-HBs before or at the start of therapy. 3, 1

• Do not delay anticancer therapy while awaiting HBV test results or hepatology consultation 3, 1
• For HBsAg-positive patients, mandatory antiviral prophylaxis for duration of therapy plus at least 12 months after last anticancer therapy 3, 1
• Reactivation risk ranges from 3-45% depending on regimen, with highest risk from anti-CD20/CD52 monoclonal antibodies, high-dose corticosteroids, and hematopoietic stem cell transplant 1, 2

Additional Management Considerations

Vaccination and Screening

• Test all household and sexual contacts for HBsAg and anti-HBs, and vaccinate seronegative contacts immediately 1, 2
• Vaccinate against hepatitis A if anti-HAV negative, as coinfection increases mortality by 5.6-29 times 1
• Screen for coinfections: anti-HCV, anti-HDV (if history of injectable drug use), anti-HIV 1

Transmission Prevention

• Cover open wounds and clean blood spills with bleach, as HBV can survive on environmental surfaces for at least 1 week 1
• Counsel on alcohol abstinence, as even limited consumption worsens outcomes 1

Common Pitfalls to Avoid

• False-positive anti-HBc can occur after IVIG administration with 15% passive transfer rate - consider this in the clinical context 1
• Do not use anti-HBs status alone to guide prophylaxis decisions - the 2025 AGA guideline notes this is not supported by evidence 3
• Do not delay cancer therapy for HBV workup - screening and prophylaxis should not postpone necessary oncologic treatment 3, 1
• Isolated anti-HBc requires HBV DNA testing - do not assume resolved infection without confirming undetectable HBV DNA 1, 2