Immunological Observation Of HBeAg Positive Chronic Hepatitis B Carriers Undergoing Enticavir Treatment

Objective:To explore the clinical significance and the dynamic changes of soluble PD-1 and PD-1+CXCR5+CD4+T cells in peripheral blood in HBeAg positive chronic hepatitis B carriers(CHBc)undergoing enticavir therapy.Methods:31 cases of HBeAg positive CHBc(group A)and 32 cases of HBeAg positive chronic hepatitis B(group B)were treated with enticavir,another15 cases of HBeAg positive CHBc(group C)were enrolled as control group.Peripheral blood and clinical data were collected at 0,24,48 weeks,PD-1+CXCR5+CD4+ T cells were accessed by flow cytometry,soluble PD-1 were measured by enzyme-linked immuno sorbent assay(ELISA).Results:At 0 week,the level of serum HBsAg,HBeAg and HBV DNA in group A and group C were significantly higher than those in group B;However,PD-1+CXCR5+CD4+ T cells in group B(4.70%±1.58%)weresignificantly higher than those in group A(3.25%±1.01%)and group C(2.77%±0.67%)(P <0.05),sPD-1 in group B(1866.62±1472.70pg/mL)was significantly higher than those in group A(824.86±538.66pg/mL)and group C(618.19±602.62pg/mL)(P <0.05).At 24 weeks,the level of serum HBsAg and HBeAg in group A and group C was not significantly decreased and significantly higher than that in group B(P <0.05);HBV DNA in both group A and group B were significantly decreased(P <0.05),and significantly lower than that in group C(P <0.05);The level of PD-1+CXCR5+CD4+ T cells were significantly decreased(P <0.05)in group A(2.26%±0.55%)and group B(2.09%±0.84%)(P <0.05),there was no significantly change in the group C(2.46%±0.77%)(P> 0.05);The level of sPD-1 was significantly decreased in group A(510.32±288.57pg/mL)and group B(658.06±432.19pg/mL)(P <0.05),there was no significantly change in group C(587.15±486.26pg/mL)(P> 0.05).At 48 weeks,the level of serum HBsAg in group A and group C was not significantly decreased and significantly higher than that in group B(P<0.05);The level of serum HBeAg was significantly decreased in group A and group B,but which in group A was significantly higher than that in group B(P<0.05);HBV DNA in both group A and group B were significantly decreased(P <0.05),and significantly lower than that in group C(P <0.05);The level of PD-1+CXCR5+CD4+ T cells were significantlydecreased(P <0.05)in group A(1.56%±0.73%)and group B(1.32%±0.43%)(P <0.05),there was no significantly change in the group C(2.64%±0.85%)(P> 0.05);The level of sPD-1 was significantly decreased in group A(289.05±215.86pg/mL)and group B(236.01±173.92pg/mL)(P<0.05),there was no significantly change in group C(650.34±598.46pg/mL)(P> 0.05).Correlation analysis: In group A at 48 weeks,the change of both PD-1+CXCR5+CD4+ T cells and sPD-1 were positively correlated with that of HBeAg at 48 weeks(r=0.376,P<0.05;r=0.598,P<0.05),but not significantly correlated with that of HBsAg(r=0.166,P>0.05;r=0.311,P>0.05);The change of sPD-1 was positively correlated with that of HBV DNA(r=0.384,P<0.05),however,the latter was not significantly correlated with that of PD-1+CXCR5+CD4+ T cells(r=0.285,P>0.05).In group B at48 weeks,the change of PD-1+CXCR5+CD4+ T cells and sPD-1 were positively correlated with those of HBsAg,HBeAg and HBV DNA.Conclusions:The viral load and e antigen of hepatitis B virus was significantly decreased in HBeAg positive chronic hepatitis B carriers treated with 48 weeks of antiviral therapy,not only related to entecavir,but also related to the immunological mechanisms involved in reduced PD-1+CXCR5+CD4+T cells and sPD-1...