摘要
目的观察乙型肝炎表面抗原(HBsAg)疫苗负载的自体树突状细胞(DC)治疗慢性乙型肝炎(CHB)的临床效果。 方法 试验19例CHB患者,取静脉外周血,用密度梯度离心及贴壁法获得单核细胞;用粒细胞一巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)细胞因子诱导扩增出DC;于第7天用HBsAg致敏后经皮下回输入患者体内,共回输两次(间隔两周)。治疗后,每隔两个月检测受试者的肝功能、HBV DNA定量及血清乙型肝炎标志物。 结果 截止2002年11月的随访结果,57.9％(11/19)的患者发生了不同程度的应答反应,HBeAg的阴转率为52.6％(10/19),HBeAg/抗-HBe血清转换率为26.3％(5/19),HBV DNA定量的拷贝数下降101.77±2.39(t=3.13,P<0.01),两例联合拉米夫定治疗的患者出现较完全的应答,DC疗法与另两种抗病毒方法效果间差异无显著性;试验前患者肝功能的高低与试验有效率间并无显著相关性。 结论 在体外诱导扩增的自身DC细胞,经HBsAg致敏后皮下回输,可有效抑制HBV的复制,减少血内病毒载量,清除HBeAg和促进HBeAg/抗-HBe的血清转换。在试验前丙氨酸氨基转移酶(ALT)高或正常的患者均可对DC治疗发生应答。DC联合拉米夫定治疗可达快速清除病毒的效果。
Objective To investigate the treatment effect of autologous HBsAg-loaded dendritic cells (DCs) on patients with chronic hepatitis B (CHB). Methods Monocytes were isolated from fresh peripheral blood of 19 CHB 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 seven days. After being incubated with HBsAg for two hours, DCs were injected to patients subcutaneously twice at the interval of two weeks. HBV DNA level, alanine aminotransferase (ALT) level, and HBV markers in the serum of patients were tested every two months. Results 11 of the 19 (57.9%) patients responded to DC-treatment clinically. The rates of HBeAg clearance and HBeAg/anti-HBe seroconversion were 52.6% (10/19) and 26.3% (5/19) respectively, and the copies of HBV DNA decreased by 101.77±2.39 (t = 3.13, P < 0.01). Two patients who were treated in combination with lamiyudine had complete clinical response. There was no difference in the trial effect between the DC treatment and the other two antiviral methods, and in the efficient rate between the patients whose ALT levels were high before treatment and those whose ALT levels were normal. Conclusions The autologous HBsAg-loaded DCs can effectively suppress HBV replication, reduce virus load in serum, eliminate HBeAg and promote HBeAg/ anti-HBe seroconversion. The patients whose ALT levels are high or normal can response clinically to DCs treatment. DCs in combination with lamivudine can eliminate virus more effectively.
出处
《中华肝脏病杂志》
CAS
CSCD
2003年第4期206-208,共3页
Chinese Journal of Hepatology
基金
国家自然科学基金(39970673)
