Recovery of host adaptive immune function promoted the reduction of hepatitis B surface antigen in nucleoside analog-experienced chronic hepatitis B patients with low hepatitis B surface antigen levels

Hepatitis B surface antigen (HBsAg) seroclearance is an optimal therapeutic endpoint, as it reflects the amount of covalently closed circular DNA. The exact mechanisms that contribute to HBsAg reduction are not completely understood. We evaluated adaptive immunity in nucleoside analog-experienced chronic hepatitis B (CHB) pa-tients with low HBsAg levels who received oral antiviral therapy. One hundred and ninety-five CHB patients had hepatitis B virus (HBV) DNA <= 1000 IU/ml and HBsAg < 3000 IU/ml for longer than one year of antiviral therapy. According to HBsAg levels, they were divided into Group 1 (HBsAg reduction >= 0.5 log10) and Group 2 (HBsAg reduction < 0.5 log10). Cytokines, adaptive immune cells, and molecular markers in peripheral blood were detected at follow-up times. In total, 38 (19.5%) of the 195 patients achieved HBsAg reduction >= 0.5 log10. IL4, IL5, IL10, TGF beta, IL17, and PD-1 decreased gradually in these patients. HBsAg reduction had a link to the change in ICOSL+CD19+ B cells and CD40L+CXCR5+CD4+ Tfh cells. More CD8+ naive T lymphocytes differ-entiated into CD4+ TCMs, CD8+ TCMs and CD8+ TEMs in Group 1. Meanwhile, Group 1 exhibited elevated Th1 and Th1/Th2 levels and reduced levels of Treg versus those in Group 2. With the reduction in HBsAg, the imbalance of T-cell subsets was partially corrected; the immune activity of T cells was enhanced, and the state of immune exhaustion was alleviated to a certain extent.

Automated summary

Hepatitis B surface antigen (HBsAg) seroclearance is an optimal therapeutic endpoint in chronic hepatitis B (CHB) patients. The mechanisms contributing to HBsAg reduction remain unclear. In this study, HBsAg reduction was associated with decreased levels of certain cytokines and changes in adaptive immune cells. With HBsAg reduction, T-cell subsets imbalance was partially corrected, immune activity of T cells was enhanced, and immune exhaustion was alleviated to some extent.