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.

Keywords: Cytokines; Hepatitis B, Chronic; T-Lymphocytes, Regulatory; Th17 Cells.

Figure 1.. The Changes of Treg and Th17 Cells in Different Responders CHB Patients Before and After Nucleos(t)ide Analogues Antivirus Therapy

A representative CD127 low expression in CD4 + CD25 high T subsets from each response group was shown. B representative IL-17A expression in CD3 + CD8 T subsets (CD4 + subsets) form each response group was shown. The mean percentage of positive cells was shown in each panel.

Figure 2.. The Correlation Between Treg Cells Frequencies, HBV DNA Loads, and ALT Levels

The Spearman's rank correlation was performed between the variables. The frequencies of Treg cells were positively correlated with HBV DNA load (A) and ALT levels (B). And the HBV DNA load was positively correlated with ALT levels (C).