Dynamic Changes of Treg and Th17 Cells and Related Cytokines Closely Correlate With the Virological and Biochemical Response in Chronic Hepatitis B Patients Undergoing Nucleos(t)ide Analogues Treatment

Abstract

Background:The restoration of HBV-specific T-cell response during antiviral therapy is associated with CD4+T-cell activity. Treg cells and Th17 cells are subtypes of CD4+T cell. However, it has remained unknown how the Treg and Th17 cells and their associated cytokines affect nucleos(t)ide analogues (NA) antiviral efficacy.Objectives:The aim of the present study was to provide a new insight to evaluate the NA antiviral therapy for patients with chronic hepatitis B (CHB).Patients and Methods:Forty-four CHB patients hospitalized between July 2010 and August 2011 were enrolled in this study. They were received NA (entecavir, lamivudine and adefovir) treatment for 14.42 ± 13.08 weeks, and the peripheral blood was collected. The frequencies of Treg and Th17 cells were detected by flow cytometric analysis, and the levels of IL-10, TGF-β1, IL-17 and IL-23 were measured by enzyme-linked immunosorbent assay (ELISA).Results:In complete and partial-responders, Treg cells frequencies and IL-10, TGF-β1, IL-23 levels were all decreased significantly after NA therapy, while Th17 cells and the IL-17 levels were increased slightly. Treg/Th17 ratio was only dramatically declined in complete-responders. But there was no significant difference in non-responders. Either HBV DNA decreased by at least 2 log copies /mL or ALT turned to normal level, Treg cells frequencies and IL-10, TGF-β1, IL-23 levels were significantly reduced. Meanwhile, Treg cells were positively correlated with HBV DNA and ALT.Conclusions:The changes of Treg and Th17 cells and their associated cytokines were related to virological and biochemical responses.

Slow reduction of IP-10 Levels predicts HBeAg seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment

“…Interestingly, levels of the various cytokines and chemokines tested were significantly reduced after 1 year of antiviral treatment. This suggests that after HBV replication was effectively inhibited by ETV, the immune response of the patients also underwent significant changes28. Results suggest that the inflammatory response decreased, damage of liver was reduced and the ability of the body to the clear the virus gradually recovered.…”

Role of Tim-3 in hepatitis B virus infection: An overview

“…Moreover, the differentiation pathways of Th17 cells and Tregs are controlled by similar cytokines, and the Treg/Th17 ratio is strongly associated with HBV load. Furthermore, imbalance of the Treg/Th17 ratio is involved in HBVrelated diseases and may become a novel drug target in the future [34,35] . HBV has also been reported to enhance the function of Tregs.…”

Th17/Treg cell expression in children with primary nephritic syndrome and the effects of ox-LDL on Th17/Treg cells

“…Shao et al (2009) believed that Th17 and Treg cells have an obvious effect on the maintenance of inflammatory and immune homeostasis. Reducing Treg cells and increasing Th17 cells can lead to the incidence of renal allograft rejection, lupus nephropathy, immunoglobulin A(IgA) nephropathy, hyperplasia of glomerular nephritis, nephritis, acute coronary comprehensive syndrome, allergic purpura, and other diseases (Turner et al, 2010;Yu et al, 2013;ZambranoZaragoza et al, 2014;Feng et al, 2015;Tabarkiewicz et al, 2015) .…”