Changes of Th1/Th2 cells and related cytokine levels in patients with chronic hepatitis B fibrosis / 中华临床感染病杂志

ABSTRACT

Objective To investigate the changes of Th1/Th2 cells and related cytokine levels in chronic hepatitis B (CHB) fibrosis.Methods Forty-six patients with CHB fibrosis underwent liver biopsy during March and October,2011.According to the stage of fibrosis,the patients were divided into S0-1 group (n =15),S2-3 group (n =20) and S4 group (n =11).Ten healthy subjects served as controls.The frequencies of circulating Th1,Th2 cells were detected by flow cytometry.The expressions of interferon-γ (IFN-γ) and interleukin 4 (IL-4) mRNA in peripheral blood mononuclear cells (PBMCs) were detected by real-time quantitative PCR.The serum IFN-γand IL-4 concentrations were determined by enzyme-linked immunosorbent assays.Intrahepatic expressions of IFN-γ and IL-4 were detected by immunohistochemical staining.Differences between groups were analyzed using non-parametric Kruskal-Wallis H test,followed by Mann-Whitney U test for multiple comparisons.Logistic regression was used for multivariate analysis.Results With the degree of liver fibrosis exacerbations,the peripheral Th1/Th2 cells frequencies ratio,IFN-γ/IL-4 mRNA ratio in PBMCs,serum IFN-γ/IL-4 ratio and intrahepatic IFN-γ/IL-4 ratio were declined (x2 =36.259,40.822,26.321 and 31.852,respectively,all P ＜ 0.05).Serum and intrahepatic IFNγ/IL-4 ratio were negatively associated with the stage of liver fibrosis (r =-0.616 and-0.531,P ＜0.01).Logistic regression analysis showed that AST,PT and the serum IFNγ/IL-4 ratio were the risk factors for significant liver fibrosis (S2-4) (OR =5.933,95％ CI1.324-26.586,P =0.02; OR =12.866,95％CI1.746-94.788,P =0.01; OR=4.755,95％CI1.034-21.862,P =0.04).Conclusions The CHB patients has imbalanced Th1/Th2 ratio.With the degree of liver fibrosis exacerbations,Th1/Th2 cytokines drift into Th2 lymphocyte sub-cluster,which suggests that Th1/Th2 imbalance may be involved in the pathogenesis of CHB fibrosis.