Peg-IFN-? Combined With NAs Therapy Accelerate HBsAg Loss In NAs-experienced CHB Patients By Enhanced CD56^briNK Cells

Objective:Previous studies have confirmed that after NAs-experienced CHB patients achieved low HBsAg levels,part of immune function was recovered.Peg-IFN-?combined with NAs therapy can effectively improve the clinical cure rate of CHB patients,especially in NAs-experienced CHB patients.However,its immune function is still unclear.MethodsOf the 40 patients with NAs-experienced CHB patients,7 patients were converted to Peg-IFN-?combined with NAs treatment?combination treatment group?,the rest 33 patients continued to receiving NAs treatment?NAs treatment group?.PBMCs were obtained from all samples at baseline?4w?12w?24w?36w?48w?72w?96w?120w?144w,and the frequencies and absolute numbers of peripheral blood NK cells,proportions of peripheral blood DC cells,CD4⁺T cells,CD8⁺T cells,Th cells,Treg cells,B cells and Tfh cells as well as surface molecules of immune cells PD-1?ICOS?IL-21?CD40L?ICOSL?CD40?PD-L1?CTLA-4?Tim3 were evaluated by flow cytometry,and HBV-DNA level,HBsAg level,Hb,ALT,AST were also detected.Results?1?Patients who receiving combination treatment were more capable of reducing HBsAg than those who receiving NAs treatment,only patients receiving combination treatment achieved HBsAg loss.?2?The absolute number of white cells,lymphocyte,neutrophil granulocyte and platelets absolute number decreased after PEG-IFN-?treatment.?3?The frequencies and absolute numbers of CD56^briri NK cells in combination treatment group increased significantly compared with NAs group,also the frequencies of CD56^briri NK cells are higher at the end of treatment with Peg-IFN-??EOT?than baseline?BL?in the combination treatment group,whereas the frequencies and absolute numbers of CD56^dimim NK cells were decreased accordingly.There was no significant difference in DC cells and adaptive immune response between the two treatment groups.?4?By longitudinal analysis of NAs group,the proportions of CD4⁺T_N cells,CD8⁺T_N cells,CD19⁺B cells and CTLA-4⁺CD4⁺T cells were increased significantly.And the proportions of CD4⁺T_EM cells,CD8⁺T_EM cells,CD25⁺CD4⁺Treg cells,CD25^hiCD4⁺Treg cells and CD127^lowCD25⁺Treg cells,PD-1⁺CD4⁺T cells and PD-1⁺CD8⁺T cells,CTLA-4⁺CD8⁺T cells,CCR4⁺CD25⁺Treg cells and CCR4⁺CD25^hii Treg cells were statistically decreased.ConclusionFor NAs-experienced CHB patients who achieved low HBsAg levels,combination treatment is more likely to achieve HBsAg decline and HBsAg clearance,increased of CD56^bri NK cells in peripheral blood may contribute to HBsAg decline and clearance.And also,partial immune function recovered after continued NAs treatment.