脐血来源或自体细胞因子诱导的杀伤细胞联合干扰素治疗慢性乙型肝炎的安全性和有效性分析

目的观察应用脐血和自体细胞因子诱导的杀伤细胞(CIK细胞)联合干扰素治疗慢性乙型肝炎(CHB)的安全性和有效性。方法 30例CHB患者均为解放军第一○五医院感染科2010年10月-2013年6月住院患者,签署临床实验研究入组同意书后随机分为3组,每组10例,治疗组分别给予脐血或自体CIK细胞移植,同时给予干扰素治疗,对照组仅接受干扰素治疗,观察治疗后4、12周患者外周血ALT、HBV血清学标志物(HBV M)、HBV DNA对数值和CD4+/CD8+水平的变化。两样本均数比较采用配对t检验或成组t检验。结果脐血或自体CIK细胞移植后12周,患者外周血ALT、HBeAg、HBV DNA对数值分别为(22.6±14.4)和(32.9±15.3)U/L;(12.5±5.8)和(18.4±8.8)PEIU/ml;(3.2±0.7)和(3.7±0.6),与对照组相比均明显降低(t=2.80~5.45,P0.05)。两治疗组治疗4周后CD4+和CD4+/CD8+水平均较对照组明显升高(t=2.21~2.43,P0.05);两组移植患者术中均未出现严重不良反应,无与移植相关的严重并发症发生。结论人脐血和自体CIK细胞移植治疗CHB,短期内可明显抑制病毒复制,改善患者肝功能和临床症状,并能提高患者细胞免疫水平,具有良好的安全性。

Efficacy and safety of UCB- derived or autologous CIK cells combined with interferon therapy in patients with chronic hepatitis B

Objective To investigate the efficacy and safety of umbilical cord blood（ UCB）- derived or autologous cytokine- induced killer（ CIK） cells combined with interferon therapy in patients with chronic hepatitis B（ CHB）. Methods Thirty CHB patients hospitalized in the Department of Infectious Diseases from October 2010 to June 2013 were included in the study. These patients were randomly and equally divided into first and second treatment groups and control group. The first or second treatment group underwent transplantation of UCB- derived or autologous CIK cells combined with interferon therapy; the control group received interferon therapy alone. At 4 and 12 weeks after treatment,alanine aminotransferase（ ALT）,serum hepatitis B virus（ HBV） marker,HBV DNA,and CD4＋/CD8＋ratio in peripheral blood were measured. Comparison of means was made by paired t test or independent- samples t test. Results At 12 weeks after transplantation of UCB- derived or autologous CIK cells,the first or second treatment group had ALT,HBeAg,and HBV DNA levels of（ 22. 6 ± 14. 4） or（ 32. 9 ± 15. 3）U /L,（ 12. 5 ± 5. 8） or（ 18. 4 ± 8. 8） PEIU /ml,and（ 3. 2 ± 0. 7） or（ 3. 7 ± 0. 6） log10 copies /ml,respectively,significantly lower than those for control group（ t = 2. 80 ～ 5. 45,P〉0. 05）. At 4 weeks after transplantation,the two treatment groups had significantly increased CD4＋levels and CD4＋/CD8＋ratios compared with the control group（ t = 2. 21 ～ 2. 43,P〉0. 05）. No severe adverse reactions and transplantation- related severe complications were found in the two treatment groups. Conclusion For CHB patients,transplantation of UCB- derived or autologous CIK cells significantly inhibits virus replication rapidly,improves liver function,relieves clinical symptoms,improves cellular immunity,and has high safety.