抗HBV-DC治疗慢性HBV携带者的初步临床研究

Clinical research on the treatment effect of anti-HBV dendritic cell on chronic HBV carrier patients

目的:观察HBsAg致敏患者自体外周血单个核细胞(PBMC)来源的树突状细胞(DC)疫苗(简称抗HBV-DC)治疗慢性HBV携带者的临床效果。方法:15例HBeAg阳性和5例HBeAg阴性的慢性HBV携带者接受临床试验。取外周静脉血25ml,用密度梯度离心及贴壁法获得单核细胞,以粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)诱导扩增出DC,并予HBsAg致敏DC。第7天收获DC静脉回输,1次/周,共4次。治疗前后检测HBV标志物定量、HBV-DNA定量及肝功能。结果:治愈1例,好转18例,无效1例,总有效率为95%(19/20),治愈率5%(1/20)。结论:抗HBV-DC静脉回输可有效地抑制慢性HBV携带者的病毒复制,降低并清除病毒抗原,促进HBeAg/HBeAb的血清学转换,是一种安全、有效的治疗慢性HBV携带的方法。

Objectlve：To investigate the treatment effect of autologous HBsAg-loaded dendritic ceils vaccine （anti-HBV DCs） on chronic HBV carrier patients.nethods：Monocytes were isolated from peripheral blood of 20 chronic HBV carrier patients by Ficoll-Hypaque density gradient centrifugating and cultured with plastic-adherence method. DCs were induced and proliferated from the monocytes with granulocyte-macrophage clony stimulating factor（GM-CSF） and interleukin-4 （IL-4） for 7 days. After being incubated with HBsAg, DCs were injected to patients＇vein for 4 times at one week＇s interval. HBV markers, HBV-DNA levels, and liver function tests in the serum of patients were tested before and after treat ment. Results：The effective rate was 95%（19/20）, and the cure rate was 5%（1/20）. The HBsAg levels were （226.05±97.85） ng/ml and （86.47±79.33） ng/ml （t=6.28,P〈0.001）, the HBeAg levels were （3.08±1.76） Ncu/ml and （1.72±1.40） Ncu/ml （t=3.37, P=0.005）, the HBeAb levels were （0.19±0.44） Ncu/ml and （0.71±1.11） Ncu/ml （t=2.61 ,P=0.021）, the HBV-DNA levels were （0.99±1.29）×10^8 copy/ml and（0.38±1.10）×10^8copy/ml （t=1.93,P=0.069）, and the ALT levels were （25.42±8.44） U/L and（34.33±22.65） U/L（t=2.05,P=0.054） before and after treatment.The HBeAg/HBeAb seroconversion was occurred in one patient. And the HBsAg and HBV-DNA were negative in one patient after treatment.Conclusion：The autologous anti- HBV DCs treatment for chronic HBV cartier patients can effectively suppress HBV-DNA replication, reduce and eliminate virus antigen in serum, increase HBeAb level and promote HBeAg/HBeAb seroconversion.