抗HBV-DC治疗非活动性HBsAg携带者的临床研究

Clinical Research of Anti-HBV Dendritic Cell for Inactive HBsAg Carrier Patients

目的观察HBsAg致敏患者自体外周血单个核细胞来源的树突状细胞疫苗治疗非活动性HBsAg携带者的临床效果。方法17例非活动性HBsAg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和白细胞介素-4诱导扩增出树突状细胞,并予HBsAg致敏树突状细胞。第7天收获树突状细胞静脉回输,每周1次,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4例,好转13例,有效率为100%,治愈率23.53%。治疗前后HBsAg为(106.68±116.45)ng/mL和(37.68±55.25)ng/mL(t=3.70,P=0.002),平均下降65%,4例HBsAg转阴。治疗前后ALT为(20.86±5.15)U/L和(26.61±13.80)U/L(t=2.154,P=0.047);HBsAb、HBeAb、HBcAb及TBIL无显著变化。结论抗HBV-DC静脉回输可显著降低并清除HBsAg,彻底治愈非活动性HBsAg携带者,是一种安全、有效的治疗非活动性HBsAg携带者的方法,显示出良好的临床应用前景。

Objective To investigate the treatment effect of autologous HBsAg-loaded dendritic cells vaccine （anti-HBV DCs） on inactive HBsAg carrier patients. Methods Monocytes were isolated from peripheral blood of 17 inactive HBsAg 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 into 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 treatment. Results The effective rate was 100%（17/17）,and the curative rate was 23.53%（4/17）. The HBsAg levels were（106.68±116.45） ng/mLand（37.68±55.25） ng/mL（t=3.70,P=0.002）,and the ALT levels were（20.86 ± 5.15 ） U/L and（26.61 ± 13.80）U/L （t= 2.154,P= 0.047） before and after treatment. And 4 patients＇ HBsAg was negative after treatment. Conclusion The autologouts anti-HBV DCs treatment for inactive HBsAg carrier can effectively reduce and eliminate HBsAg, and can cure those inactive HBsAg carrier patients.