| Background and Objective:So far,chronic hepatitis B(CHB)is still a type of infectious disease that seriously threatens the safety of life and property of the public in our country,and functional cure is currently our ideal goal for the treatment of CHB.Hepatitis B virus(HBV)interacts with the host immune system to establish a balanced state in the patient’s body,allowing HBV to exist in the body for a long time.To achieve the goal of"functional cure",enhancing the immune function of the host is one of the key factors that we cannot ignore.Pegylated interferon(Peg-IFN),as the first-line drug for CHB therapy,has a direct anti-HBV effect,and its immunomodulatory function has a profound and extensive impact on the host’s immune system.In this study,HBeAg-negative CHB patients who received Peg-IFN treatment were used as the research objects to analyze the clinical and immune factors that affect the rapid decline of HBsAg in the early stage of treatment and the realization of functional cure,and to explore the correlation between host immune function and the efficacy of Peg-IFN in the treatment of CHB.Provide a theoretical basis for predicting the efficacy of Peg-IFN against HBV and finding new CHB therapeutic targets.Method:1.Enrolled 204 CHB patients who were admitted to the Department of Infectious Diseases,First Affiliated Hospital of Chongqing Medical University from April 2017 to 2020.8.Collected the medical history data of the subjects and used statistical methods to study the factors affecting the rapid decline of HBsAg in the early stage of Peg-IFN anti-HBV treatment and the realization of functional cure;2.Specimens collection and processing:Collected peripheral blood samples of some subjects and 10 healthy volunteers,and extracted plasma and peripheral blood mononuclear cells(PBMC);3.Analysis of the correlation between the distribution and dynamic changes of peripheral blood T lymphocytes and the rapid decline of HBsAg in the early stage of treatment:analyzed the distribution and dynamic changes of peripheral blood CD4~+T cells,CD8~+T cells and Treg cells of healthy people and CHB patients at different treatment time points(baseline,treatment 12w,treatment 24w,and achieve functional cure)by flow cytometry,and explored the correlation between these changes and the rapid decline of HBsAg in the early stage of Peg-IFN anti-HBV treatment;4.Correlation analysis between the CXCR5/CXCL13 axis and the rapid decline of HBsAg in the early stage of treatment:Flow cytometry was used to analysis the distributions and dynamic changes of peripheral blood follicular helper T cells(Tfh,CXCR5~+CD4~+T cell)and follicular cytotoxic T cells(Tfc,CXCR5~+CD8~+T cell);Enzyme-linked immunosorbent assay(ELISA)was uesd to detect the level of CXCL13 in plasma,and explored the correlation between the CXCR5/CXCL13 axis and the rapid decline of HBsAg in the early stage of treatment;5.Statistics:used SPSS19.0 and Graph Pad Prism 8.0 for mapping and analysis.In the measurement data,the t-test was used for the comparison between groups that conformed to the normal distribution and the homogeneity of variance;the Welch’s corrected t test was used for the uneven variance;the Mann-Whitney rank sum test was used for the non-uniformity.Counting data mainly adopted Chi-square test or Fisher’s exact test.Logistic stepwise regression analysis method was used to analyze the influencing factors of early HBsAg rapid decline and functional cure.When P<0.05,the difference was considered to be statistically significant.Result:1.Gender,age,and AST at 12 weeks of treatment were independent influencing factors for the rapid decline of HBsAg in the early stage of Peg-IFN treatment(early response).For women,the younger the age and the higher the level of AST at 12 weeks of treatment,the greater the possibility of a rapid decline in HBsAg in the early stage of treatment;2.The rapid decline of HBsAg in the early stage of treatment,HBsAg and ALT at baseline were independent influencing factors for the functional cure(HBsAg clearance)of Peg-IFN treatment of CHB.To achieve early response,the lower the level of HBsAg and ALT at baseline,the greater the possibility of HBsAg clearance(functional cure);3.The distribution and dynamic changes of peripheral blood T lymphocytes in the early treatment period were related to the efficacy of Peg-IFN against HBV.Compared with other T lymphocytes,CD8~+T cells played a more important role in Peg-IFNα-2b anti-HBV and were related to the rapid decline of HBsAg.At the same time,the increasing trend of the percentage of CD8~+T cells to total T cells during the treatment process and the decrease in the ratio of CD4/CD8 due to its increase could well predict the efficacy of Peg-IFNα-2b against HBV;4.The decline of CXCR5~+CD4~+T cells in the early treatment period might indicate the poor response of Peg-IFN to HBsAg;Tfh cells always maintained a high level during the process of Peg-IFN anti-HBV,which may be related to the rapid decline of HBsAg;5.CXCR5~+CD8~+T cells had the function of anti-HBV,which was related to the rapid decline of HBsAg;the possible mechanism was through their own stem-like characteristics,that was,self-renewal and differentiation into end-stage effector cells(CXCR5~-CD8~+subgroup)to exert anti-HBV features;6.The high level of CXCL13 and the rapid rise of CXCL13 in the early treatment could be used as indicators for us to predict the efficacy of Peg-IFNα-2b in the treatment of chronic hepatitis B.CXCL13 played an important antiviral function for HBV.Conclusion:The rapid decline of HBsAg in the early stage is the first step for CHB to pursue a functional cure.The distribution and dynamic changes of peripheral blood T lymphocytes in the early treatment period are related to the efficacy of Peg-IFNα-2b against HBV.Among them,CD8~+T cells dominate and are related to the rapid decline of HBsAg.At the same time,the CXCR5/CXCL13 axis plays an important role in the process of Peg-IFN anti-HBV,and can be used as a new entry point for us to treat chronic hepatitis B,predict and achieve functional cure. |
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