CIK细胞治疗慢性乙型肝炎的疗效观察

Treatment with autologous cytokine-induced killer cells in patients with chronic hepatitis B

目的观察自体细胞因子诱导的杀伤(cytokine-induced killer,CIK)细胞治疗慢性乙型肝炎的疗效及安全性,探索慢性乙型肝炎治疗的新策略。方法采集32例e抗原阳性的慢性乙型肝炎患者外周血单个核细胞,在体外经干扰素γ、白细胞介素-2、抗CD3单克隆抗体等细胞因子诱导成CIK细胞,分次自体回输,观察治疗前及治疗后第1、4、12周肝功能、HBV血清标志物和HBV DNA水平并进行比较分析,同时对不良反应和肾功能进行评估。结果 32例CIK细胞均诱导成功。在治疗过程中除回输时大部分患者出现一过性发热外,无其他明显不良反应,肾功能和血细胞无异常变化。治疗结束后随着观察时间的延长,ALT和AST水平等肝功能指标明显改善(第1、4、12周ALT复常率为31.2%、62.5%、75.0%,AST复常率为53.1%、65.6%、81.3%);第1、4、12周e抗原转阴率为50.0%、59.4%、62.5%,e抗原血清转换率比例为18.8%、28.1%、31.3%。治疗结束1周内HBVDNA水平无明显变化,但随着观察时间的延长HBVDNA水平有明显下降,第1、4、12周以下降2个log为观察指标,其同基线水平相比下降的比例分别为12.5%、31.2%、53.1%,如果以DNA低于不可检测水平以下为观察指标,同基线水平相比下降的比例是3.1%、12.5%、34.3%。结论本研究提示CIK细胞治疗慢性乙型肝炎后在12周观察期内是安全有效的。特别是治疗后随着观察时间的延长,HBVDNA复制水平逐渐下降,提示CIK细胞治疗后可能存在持续的免疫应答反应。

Objective To evaluate the safety and efficacy of the treatment with autologous cytokine-induced killer （CIK） cells in patients with chronic hepatitis B （CHB） and to investigate a new therapeutic strategy for CHB. Methods Peripheral blood mononuclear cells （PBMCs） were isolated from 32 HBeAg-positive CHB patients, and then induced with cytokines such as interferon （IFN） y,interleukin （IL）-2 and monoclonal antibody （mAb） against CD3 to CIK cells in vitro. The autologous CIK cells obtained were infused back to the individual patient. Liver function parameters, serum markers and HBV DNA levels were observed and com- pared before treatment and at week 1, 4 and 12 after treatment. Meanwhile, adverse reactions and kindney function were evaluated. Results CIK cells were induced successfully in 32 patients. During the treatment, no obvious adverse reactions were seen except fever in most of the patients when and after CIK cells were infused. There were no significant differences in kidney function and hemocytes. ALT and AST levels improved significantly after treatment. At week 1, 4 and 12 after treatment, ALT normalization rates were 31.3%, 62.5% and 75.0%, AST normalization rates 53.1%, 65.6% and 81.3%, HBeAg negative rates 50.0%, 59.4% and 62.5%, and HBeAg seroconversion rates 18.8%, 28.1% and 31.3%, respectively. HBV DNA levels didn＇t show any significant change at week 1 after treatment, and decreased significantly as time went by. As compared with baseline levels, 12.5%, 31.2% and 53.1% of the patients had a reduction of 2 log10 in HBV DNA levels and 3.1%, 12.5% and 34.3% of the patients had HBV DNA levels below the limit of detection at week 1, 4 and 12 after treatment. Conclusions Treatment with autologous CIK cells is safe and effective in CHB patients during 12 weeks after treatment, and especially as time goes by, HBV DNA levels decrease gradually, which sug- gests sustainable immune response.