Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment
10.3760/cma.j.issn.1000-6680.2016.08.006
- VernacularTitle:慢性乙型肝炎患者抗病毒治疗与停药复发后体内乙型肝炎核心抗原特异性T淋巴细胞变化
- Author:
Bixia LIU
;
Lunli ZHANG
;
Wenfeng ZHANG
- Publication Type:Journal Article
- Keywords:
Hepatitis B;
T-lymphocytes,cytotoxic;
Antiviral treatment;
Recurrence
- From:
Chinese Journal of Infectious Diseases
2016;34(8):480-484
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the potential mechanism of severe liver injury shortly after withdrawal of antiviral therapy in chronic hepatitis B (CHB) patients.Methods Forty-nine patients with chronic hepatitis B virus (HBV) infection from the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University and 8 healthy volunteers from August 2014 to March 2015 were included in this study.All of them were human leukocyte antigen (HLA)-A2-positive.CHB patients were classified into three groups,including 15 cases in immune-tolerance group,20 cases in sustained antiviral treatment group,and 14 cases in recurrence of drug withdrawal group.The frequency of peripheral HLA-A0201-restricted hepatitis B core antigen (HBcAg)18-27 pentamer complex specific CD8+ T cells in CHB patients was analyzed by flow cytometry.Enzyme linked immunospot assay(ELISPOT) was used to detect interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) secretions of HBcAg18-27-specific CD8+ T cells.The experimental data were analyzed using non-parametric U tests.Results In healthy control group,immune-tolerance group,sustained antiviral treatment group and recurrence of drug withdrawal group,the frequencies of HBcAg-specific CD8+T cells were (0.17 ± 0.16) ％,(1.46±0.72)％,(3.24± 1.60)％ and (4.67±2.43)％,respectively.Compared with healthy control group,the difference were all statistically significant in the three groups (Z=-3.583,-4.018 and-3.823,respectively;all P＜0.01).The frequencies of HBcAg-specific CD8+T cells in immune tolerance group or recurrence of drug withdrawal group were both significantly different from that in sustained antiviral therapy group (Z=-3.400 and-2.030,respectively;both P＜0.05).The difference between immune-tolerance group and recurrence of drug withdrawal group was also significant (Z =-3.230,P＜0.01).The secretion levels of IFN-γ of HBcAg-specific CD8+T cells in healthy control group,immune-tolerance group,sustained antiviral treatment group and recurrence of drug withdrawal group were2 (0-6),16 (2-53),106 (14-254) and 156 (28-395) spot forming cell (SFC)/106 peripheral blood mononuclear cell (PBMC),respectively.The differences between healthy control group and immune-tolerance group,sustained antiviral treatment group or recurrence of drug withdrawal group were all statistically significant (Z=-3.585,-4.069 and-3.824,respectively;all P＜0.01).The IFN-γ level of HBcAg-specific CD8+ T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.205,P=0.027),and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.700,P＜ 0.01).The TNF-α levels secreted by HBcAg-specific CD8+ T cells in each group were 2 (0-5),16 (2-32),112 (15-283),and 195 (55-537) SFC/106PBMC,respectively.The differences between healthy control group and immune-tolerance group,sustained antiviral treament group or recurrence of drug withdrawal group were all statistically significant (Z=-3.619,-4.069 and-3.824,respectively;all P＜0.01).The TNF-α level secreted by HBcAg-specific CD8+T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.449,P=0.014),and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.350,P＜0.01).Conclusions The changes of frequency and immune function of HBcAg-specific CD8+T cells in CHB patients may be one of the reasons causing severe liver damage after irregular withdrawal of nucleoside analogues.
