Recovery of circulating CD56dim NK cells and the balance of Th17/Treg after nucleoside analog therapy in patients with chronic hepatitis B and low levels of HBsAg

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Background and aims

Much evidence indicates that the soluble antigens secreted by hepatitis B virus (HBV) inhibit the function of the immune system. The aim of this study is to investigate, after treatment with nucleoside (acid) analogs (NAs) and the inhibition of viral replication, whether the immune systems of patients with a peripheral blood HBV-DNA level <1000 IU/mL, hepatitis B e antigen (HBeAg) disappearance, and a decrease in hepatitis B surface antigen (HBsAg) levels could be reconstructed.


The frequency and phenotype of circulating natural killer (NK) cells, dendritic cells (DCs), T-helper (Th) cells, regulatory T (Treg) cells, CD4+, CD8+ T cells, T follicular helper (Tfh) cells and B cells subtypes were tested by flow cytometry in chronic hepatitis B (CHB) patients and healthy controls (HCs). The levels of HBV-related serum HBsAg, HBeAg, HBV-DNA load, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.


Regarding the innate immune system, an increased frequency of CD56dim NK cells was found in the therapeutic response (TR) group compared with that in the immune-active phase (IA) group. Additionally, regarding the adaptive immune system, the Th17/CD4+CD25+CD127dimTreg ratio was reduced in the TR group. Additionally, the frequency of CD40L+CXCR5+CD4+T cells and CD40+CD19+CD27+CD38+B cells was significantly higher than that of HCs, while that of PDL1+CD19+ B cells was lower. Furthermore, the frequencies of CTLA4+CD4+T cells and CTLA4+CD8+T cells in patients with CHB were significantly higher than those in HCs.


After NA treatment and the inhibition of viral replication, circulating CD56dim NK cells and the balance of Th17/Treg can be recovered. Restoring circulating CD56dim NK cells and the Th17/Treg balance may help reduce HBsAg levels in patients.

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