Combination of pegylated-interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients.

BACKGROUND & AIMS A combination of pegylated interferon-alpha (Peg-IFN-α) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear. METHODS 40 NA-experienced CHB patients were enrolled in this study. The frequencies of peripheral blood NK cells, DCs, CD4+ T cells, CD8+ T cells, Th cells, Treg cells, B cells and Tfh cells were evaluated by flow cytometry. RESULTS 7 of the 40 patients converted to Peg-IFN-α combined with NAs treatment, while the other 33 continued to NAs therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56bri NK cells in the combination treatment group increased significantly compared with the NAs treatment group, whereas the CD56dim NK cells were decreased. In the NAs treatment group, the proportions of CD4+ TN cells, CD8+ TN cells, CD19+ B cells and CTLA-4+ CD4+ T cells were increased, while the proportions of CD4+ TEM cells, CD8+ TEM cells, CD25+ CD4+ Treg cells, CD25hi CD4+ Treg cells, CD127low CD25+ Treg cells, PD-1+ CD4+ T cells, PD-1+ CD8+ T cells, CTLA-4+ CD8+ T cells, CCR4+ CD25+ Treg cells and CCR4+ CD25hi Treg cells were decreased after therapy. CONCLUSIONS For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56bri NK cells.