| Objective: 1. To explore the effect and safety of telbivudine treatment in HBs Ag-poaitive mothers on preventing the mother-to-child transmission. 2. To evaluate the effect of telbivudine treatment in HBs Ag-poaitive mothers on the ratio of immune cells.Methods: 1. A retrospective cohort study was conducted, A total of 140 HBs Ag-positive pregnant women whose HBV DNA≥106copies/m L and their infants were enrolled in this study. The mothers were recruited from the Third People’s Hospital of Taiyuan, from July 2013 to July 2015. The information of mother were acquired by a questionnaire which recorded general conditions, epidemiological data, whether to use telbivudine or not. According to According to whether to take telbivudine or not, they were divided into two groups including telbivudine-treated group(with telbivudine) and control group(without telbivudine). All neonates were vaccinated with recombinant hepatitis B vaccine 10μg. According to a standard vaccination regimen(0,1 and 6 months procedure) and one dose of 200 IU of hepatitis B immune globulin(HBIG) in 24 h after birth. Maternal elbow vein blood and neonatal femoral blood.Peripheral blood samples from the mothers were obtained before delivery and all blood samples were collected using heparinized syringes. Femoral venous blood sample of neonates was obtained before the administration of passive-active immunoprophylaxis. Non-anticoagulant peripheral blood samples from neonates(before the administration of passive-active immunoprophylaxis) and mothers(before delivery) were also collected. The infants were followed up at the age of 12±1 months. Femoral venous blood sample of infants was also obtained. All serum samples were stored at-80 ?C until use. Repeated freezing and thawing were avoided. 2. The HBs Ag, anti-HBs, HBe Ag, anti-HBe, anti-HBc in maternal peripheral blood、neonatal peripheral blood and infantile peripheral blood were measured using chemiluminescence immunoassay(CLIA) kits. 3. HBV DNA in maternal peripheral blood, neonatal peripheral blood and infantile peripheral blood were detected by fluorescene quantitative polymerase chain rection(PCR) assay. 4. T lymphocytes, B lymphocytes cell, DCs and CD4+CD25+Treg in neonatal peripheral blood and infantile peripheral blood were tested by Flow Cytometry(FCM).Results: 1 The effect of telbivudine treatment in HBs Ag-poaitive mothers on preventing the mother-to-child transmission. 1.1 The comparison of neonatal HBs Ag, HBe Ag, the HBV DNA positive rate and intrauterine transmission rate between two groups The neonatal HBs Ag, HBe Ag, HBV DNA positive rate, intrauterine transmission rate were all lower in telbivudine-treated group than control group, the difference were both not significant(P>0.05). 1.2 The comparision of infantile HBs Ag, HBe Ag, HBe Ag loss and seroconversion rate, HBV DNA-positive rate and the immune response to hepatitis B vaccine between two groups There were no significant difference in infantile HBs Ag, HBe Ag and HBV DNA-positive rate between two groups(P>0.05).The infantile HBs Ag loss and seroconversion were significantly higher in telbivudine-treated group than that of control group(c2=7.286, P=0.007; c2=6.285, P=0.012). The rate of immune response to hepatitis B vaccine in telbivudine-treated group was significantly lower than that of control group(c2=3.952, P=0.047). 1.3 The comparision of the rate of infantile HBe Ag loss and seroconversion and the immune response to hepatitis B vaccine in the pregnant women with different HBe Ag status in two groups The rate of infantile HBe Ag loss and seroconversion were both higher in telbivudine-treated group than that of control group whether the women were HBe Ag-positive or not, but there were no significant difference(P>0.05). The rate of immune response to hepatitis B vaccine in telbivudine-treated group was significantly lower than that of control group when the mothers were HBe Ag-positive(c2=4.233, P=0.040). Results from unconditional logistic regression analysis showed that the using of telbivudine(OR=0.320, 95%CI: 0.012~0.890) could be the protective factor of non/hypro response to hepatitis B vaccine. 2 The safety of telbivudine for mothers, neonate and infant between two groups There were no significant difference in maternal vaginal bleeding rate and stomachache rate between two groups(P>0.05). There were no significant difference in neonatal malformation rate and infantile pneumonia between two groups(P>0.05). 3 The effect of telbivudine treatment in HBs Ag-poaitive mothers on immune cell in peripheral blood 3.1 The effect of telbivudine treatment in HBs Ag-poaitive mothers on T lymphocytes subsets The ratio of neonatal CD3+T cell, CD8+T cell were all lower in telbivudine-treated group than those in control group, the difference were both not significant(t=1.556, P=0.124; Z=-0.419, P=0.675). The ratio of neonatal CD4+T cell was lower in telbivudine-treated group than those in control group, the difference was not significant(t=0.264, P<0.001). The ratio of neonatal CD4+T/CD8+T was higher in telbivudine-treated group than that in control group, the difference was not significant(Z=-1.867, P=0.062). The ratio of infantile CD4+T cell in telbivudine-treated group was significantly higher than that in control group(t=-2.117, P=0.038). The ratio of infantile CD3+T cell、the ratio of neonatal CD4+T/CD8+T were both higher in telbivudine-treated group than those in control group, the difference were both not significant(t=-2.020, P=0.071; Z=-1.876,P=0.061). The ratio of infantile CD8+T cell was lower in telbivudine-treated group than that in control group, the difference was not significant(Z=-5.579, P=0.563). The ratio of infantile CD4+T cell was notably increased compared to that of neonatal CD4+T cell when they were in telbivudine-treated group(t=2.999, P=0.036). 3.2 The effect of telbivudine treatment in HBs Ag-poaitive mothers on B cell The ratio of neonatal B cell was higher in telbivudine-treated group than that in control group,the difference was not significant(t=-0.055, P=0.956). The ratio of infantile B cell was higher in telbivudine-treated group than that in control group, the difference was not significant(t=-0.151, P=0.880). The infantile B cell was higher than neonatal B cell both in telbivudine-treated group and control group(P>0.05). 3.3 The effect of telbivudine treatment in HBs Ag-positive mothers on DCs The neonates and infants had higher m DC, p DC in telbivudine-treated group than those in control group, the difference were not significant(P>0.05). The infants had higher m DC, p DC than neonates both in telbivudine-treated group and control group, the difference was not significant(P>0.05). 3.4 The effect of telbivudine treatment in HBs Ag-positive mothers on CD4+CD25+Treg The neonates had higher CD4+CD25+Treg in telbivudine-treated group than that in control group, the difference were not significant(P>0.05). While the infants had lower CD4+CD25+Treg in telbivudine-treated group than that in control group, the difference were not significant(P>0.05). The infants had higher m DC, p DC than neonates both in telbivudine-treated group and control group,the difference was not significant(P>0.05). The infants had lower CD4+CD25+Treg than that of neonates both in telbivudine-treated group and control group, the difference was not significant(P>0.05).Conclusions: 1 The infantile HBs Ag loss and seroconversion were significantly higher in the group with telbivudine than that of control group, so we can suppose that telbivudine is associated with the higher rates of HBe Ag seroconversion, can inhibit HBV DNA replication, resulting in interrupting HBV mother-to-child transmission. 2 The rate of immune response to hepatitis B vaccine in telbivudine-treated group was significantly lower than that of control group, suggesting that HBs Ag positive mothers during pregnancy using telbivudine with the combined application of HBIG and hepatitis vaccine can notably decrease the rate of immune response to hepatitis B vaccine. 3 The rate of immune response to hepatitis B vaccine in telbivudine-treated group was significantly lower than that of control group when the mothers were HBe Ag-positive, which showed that the pregnant with HBe Ag positive and the high load of HBV DNA should using telbivudine to decrease the rate of immune response to hepatitis B vaccine under the permitting conditions. 4 The ratio of infantile CD4+T cell in telbivudine-treated group was significantly higher than that in control group and the ratio of infantile CD4+T cell was notably increased compared to that of neonatal CD4+T cell when they were both in the group with telbivudine and control group, and it suggests that the ratio of CD4+T cell may improved after the applyment of telbivudine with the combined application of HBIG and hepatitis vaccine, resulting the inhibition of HBV DNA replication, thereby reducing HBV mother-to-child transmission. |
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