Interpret a hepatitis B serology with negative HBsAg, positive anti‑HBs, negative HBeAg, and reactive anti‑HBc, and advise the appropriate management.

Interpretation of Hepatitis B Serology: Resolved Infection with Natural Immunity

Your serologic profile (HBsAg negative, anti-HBs positive, anti-HBc positive, HBeAg negative, anti-HBe positive) definitively indicates resolved past hepatitis B infection with natural immunity—no further routine hepatitis B testing or treatment is required. 1

Serologic Pattern Analysis

• This exact combination—negative HBsAg, positive anti-HBs, and positive anti-HBc—unequivocally confirms past HBV exposure with successful viral clearance and development of protective immunity. 1

• Anti-HBc (total) persists for life after natural HBV infection and serves as a permanent marker of prior exposure, distinguishing natural immunity from vaccine-induced immunity (which produces only anti-HBs without anti-HBc). 1

• Your anti-HBs positivity indicates protective immunity; levels ≥10 mIU/mL are considered adequate for protection against reinfection. 1

• The negative HBsAg confirms viral clearance and rules out chronic infection. 1

• The presence of anti-HBe (with negative HBeAg) is consistent with resolved infection and provides additional confirmation of your immune status. 2

Clinical Classification

• According to EASL 2017 nomenclature, you are in Phase 5: HBsAg-Negative Resolved Infection, characterized by prior HBV exposure with anti-HBc (± anti-HBs), negative HBsAg, undetectable HBV DNA, and normal ALT—representing a functional cure. 1

• The CDC and American Journal of Kidney Diseases confirm that when this serologic pattern is present in immunocompetent individuals, no further routine hepatitis B testing is required. 1

Management Recommendations

For Immunocompetent Individuals

• No ongoing monitoring, antiviral therapy, or additional hepatitis B testing is necessary. 1

• You have natural immunity and are protected against future HBV infection. 1

Critical Exception: Immunosuppression Risk

• If you ever require immunosuppressive therapy (chemotherapy, anti-CD20 agents like rituximab, high-dose corticosteroids, stem cell transplant, or other immunosuppression), you are at risk for HBV reactivation despite resolved infection. 3

• The risk of reactivation in anti-HBc-positive patients receiving immunosuppression ranges from 3-45%, with highest risk from anti-CD20 therapy or stem cell transplantation. 3

• Before any planned immunosuppressive therapy, you must undergo HBV DNA testing. If HBV DNA is detectable, antiviral prophylaxis is required similar to HBsAg-positive patients. 3

• During immunosuppression (if not on prophylaxis), monitoring of HBsAg and ALT every 3 months is recommended, with continuation for at least 12 months after completing immunosuppressive therapy. 3

Key Clinical Pearls

• Although covalently closed circular DNA (cccDNA) may persist in hepatocytes despite HBsAg clearance, this poses no risk in immunocompetent individuals. 1

• Your anti-HBs positivity provides some protection against reactivation but does not completely eliminate risk during severe immunosuppression. 3

• Isolated anti-HBc positivity (without anti-HBs) can occur when anti-HBs levels wane over time, but your profile includes both markers, confirming robust immunity. 1

• False-positive anti-HBc results are more common in low-prevalence populations, but your complete serologic pattern (with positive anti-HBs and anti-HBe) makes false positivity extremely unlikely. 1