| Objective:To detect the expression level of PD-1/D-L1in peripheral blood of patients with Chronic hepatitis B(CHB),evaluate the effect of antiviral therapy on the expression level of sPD-1/PD-L1 in peripheral blood of CHB patients,analyze the correlation between PD-1/D-L1 and ALT,AST and HBV DNA,and explore the role of PD-1/D-L1 in Chronic HBV infection.Meanwhile,the expression levels of peripheral blood T lymphocyte subsets in CHB patients,HBV carriers and healthy people were measured,and the correlation between sPD-1/PD-L1 and T lymphocyte was analyzed to explore the effect of sPD-1/PD-L1 on immune function of the body.Methods:A total of 97 patients with CHB who were initially treated with Entecavir(ETV)were selected as subjects for observation,and 51patients with CHB who were followed up to 24 weeks were treated,20healthy subjects and 20 HBV carriers at the same time were selected as the control group.Enzyme-liked immunosorbent assay was used to detect sPD-1/d-1 expression level of sPD-1/sPD-L1 in the treatment of CHB patients before and after treatment of 4 weeks,24 weeks peripheral venous blood samples,,HBV-DNA loads using the method of real-time fluorescent quantitative PCR detection,the hepatitis B virus infection markers by using chemiluminescence detection,liver function index using automatic biochemical analyzer test.the expression levels of sPD-1/PD-L1 in peripheral blood of 20 healthy subjects and 20 HBV carriers were collected in the same way as that of CHB patients.Results:1.After 4 weeks of treatment,the expression levels of ALT,AST,TBIL and DNA load of HBV in the treatment group were significantly lower than those before treatment(P<0.05).The ALT,AST,TBIL and The HBV DNA load of CHB patients after 12 weeks of treatment continued to decrease,and the difference was statistically significant(P<0.01).The peripheral blood ALT,AST,TBIL and HBV DNA were lower in 51 patients with CHB after 24weeks of treatment.The reference value(500IU/mL)was significantly different from that before treatment and the fourth week of treatment(P=0.000).2.The expression of T lymphocyte subsets in peripheral blood of patients with CHB was significantly lower than that of healthy controls and carriers(P<0.01).In the treatment group,the expression of T lymphocyte subsets in peripheral blood increased at 4 and 12 weeks after antiviral therapy,with statistically significant difference from those before antiviral treatment(P<0.01).and no statistically significant difference from those in the healthy control group and the carrier group(P>0.05).The expression of T lymphocyte subsets in peripheral blood of patients in the treatment group was significantly increased after 24 weeks of antiviral therapy,and the difference was statistically significant(P<0.01).3.The expression levels of sPD-1 and sPD-L1 in peripheral blood of 51patients with CHB before treatment were significantly higher than those in healthy control group and carrier group(P<0.01).The expression levels of sPD-1 and sPD-L1 were significantly decreased in the treatment group at 4and 12 weeks after treatment,and there were significant differences between the two groups(P<0.01).The expression levels of sPD-1 and sPD-L1 in the peripheral blood of the treatment group were significantly decreased at the24th week of antiviral therapy,and the difference was statistically significant(P<0.01),which difference from the healthy control group and the HBV carrier group was not statistically significant(P>0.05).4.The expression levels of sPD-1 and sPD-L1 in peripheral blood of 32patients with HBeAg(+)and 19 patients with HBeAg(-)were significantly higher than those of healthy control group and carrier group.P<0.01),there was no significant difference between HBeAg(+)and HBeAg(-)groups(P>0.05).At the 4th and 12th week of antiviral treatment,the expression levels of sPD-1 and sPD-L1 in HBeAg(+)and HBeAg(-)groups were significantly decreased,and there were significant differences between the healthy control group and carrier group(P<0.01).At the 24th week of antiviral treatment,the expression levels of sPD-1 and sPD-L1 in peripheral blood of HBeAg(+)and HBeAg(-)groups were significantly lower than those before treatment(P<0.01),which was better than healthy control group.There was no significant difference in the HBV carrier group(P>0.05).5.There was a positive correlation between ALT and AST expression levels in peripheral blood of patients with CHB before treatment(r=0.736,P=0.000).There was a positive correlation between ALT,AST and TBIL expression levels(r=0.376,P=0.007;r=0.589,P=0.000);there was a positive correlation between ALT expression level and HBV DNA load(r=0.492,P=0.000);there was no correlation between AST,TBIL and HBV DNA load(r=0.0291,P=0.883;r=0.492,P=0.087).There was no correlation between ALT and AST and TBIL expression levels in peripheral blood of patients in the treatment group after 24 weeks of treatment(r=0.012,P=0.935;r=-0.023,P=0.875);there was a positive correlation between AST and TBIL expression levels(r=0.373,P=0.007);There was no correlation between ALT,AST,TBIL expression levels and HBV DNA load(r=0.053,P=0.711;r=-0.059,P=0.682;r=0.080,P=0.577).6.There was a positive correlation between ALT,AST,TBIL expression,HBV DNA load and sPD-L1 level in patients with CHB before treatment(r=0.451,P=0.001;r=0.460,P=0.001;r=0.434,P=0.001;r=0.359,P=0.010);there was no correlation between ALT,AST,TBIL expression level,HBV DNA load and sPD-1 expression level.There was no correlation between ALT,AST,TBIL expression,HBV DNA load and sPD-1/sPD-L1 levels in peripheral blood of patients with CHB after 24 weeks of treatment.7.There was a positive correlation between sPD-1and CD3~+T and CD4~+Tand CD8~+T lymphocyte subsets in patients with CHB before treatment(r=0.403,P=0.003;r=0.408,P=0.003;r=0.372,P=0.007);sPD-1 was not associated with sPD-L1 expression level(r=-0.038,P=0.794);sPD-L1 and CD3~+T,CD4~+T,CD8~+T lymphocyte subsets were expressed There is no significant correlation between levels.There was no significant correlation between the expression levels of sPD-1 and sPD-L1 and CD3~+T,CD4~+T and CD8+T lymphocyte subsets in peripheral blood of patients in the treatment group after 24 weeks of treatmentConclusions:1.Antiviral therapy can effectively inhibit HBV DNA replication,reduce liver tissue inflammation,and promote liver function recovery.2.The expression levels of sPD-1,sPD-L1 and T lymphocyte subsets in peripheral blood of patients with CHB were unbalanced,and the expression levels of sPD-1 and sPD-L1 were gradually decreased after antiviral therapy,CD3~+T,CD4~+T,CD8~+T The expression level of lymphocyte subsets gradually increased.3.There was no correlation between the expression levels of sPD-1 and sPD-L1 in peripheral blood of patients with CHB and the expression pattern of HBeAg.4.There was a positive correlation between sPD-L1 and ALT,AST,TBIL expression and HBV DNA load,suggesting that sPD-L1 may be involved in the development of CHB.5.There was a positive correlation between sPD-1 and CD3+T and CD4~+T and CD8~+T lymphocyte subsets in CHB patients,suggesting that sPD-1 can effectively block PD-1/PD-L1 pathway and promote lymphocytes activatly proliferation. |
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