Seroclearance of HBsAg in Chronic Hepatitis B Patients after a Tolerance Breaking Therapy: GM-CSF, followed by Human HBV Vaccine

Objective: Seroclearance of hepatitis B surface antigen (HBsAg) remains a challenge to the functional cure of HBV infection due to an HBV-specific immune tolerance that prevents virus eradication. Methods: In this clinical study, chronic hepatitis B patients treated with the standard nucleotide analog (NA) Adefovir Dipivoxil (ADV) or treated with ADV and IFN- were immunized with granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with Human HBV Vaccine. Results: This THRIL-GM-Vac approach (THRee Injections of Low-dose GM-CSF followed by one dose of the HBV Vaccine) has achieved at least a 10-fold reduction of HBsAg level in 10 out of 23 (43.5%) patients tested. Moreover, two out of the 10 patients eventually reached seroclearance. Thus THRIL-GM-Vac could break HBV-specific tolerance and boost HBsAg-specific cellular immunity. Consequently, the THRIL-GM-Vac approach could provide an effective therapy for patients bearing medium-to-low levels of HBsAg. Conclusion: Our findings carry the clinical significance of showing a novel way to break immunotolerance that can tackle the persistent infection manifested as chronic HBV burden in chronic hepatitis B (CHB) patients.