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.
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.


METHODS
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.


RESULTS
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.


CONCLUSION
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.
['Liu|Nianqiu|N|', 'Liu|Bin|B|', 'Zhang|Li|L|', 'Li|Hu|H|', 'Chen|Zhiwei|Z|', 'Luo|Aoran|A|', 'Chen|Min|M|', 'Peng|Mingli|M|', 'Yin|Wenwei|W|', 'Ren|Hong|H|', 'Hu|Peng|P|']
D000328:Adult D000998:Antiviral Agents D019002:CD56 Antigen D016022:Case-Control Studies D004279:DNA, Viral D005260:Female D006147:Guanine D006514:Hepatitis B Surface Antigens D006513:Hepatitis B e Antigens D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D006801:Humans D007694:Killer Cells, Natural D008297:Male D008875:Middle Aged D012720:Severity of Illness Index D050378:T-Lymphocytes, Regulatory D058504:Th17 Cells D016896:Treatment Outcome D019562:Viral Load D055815:Young Adult
Nucleoside analogs Hepatitis B virus Natural killer cells Regulatory T cells T-helper cells