柴胡解毒汤联合阿德福韦酯治疗慢性乙型肝炎患者外周血淋巴细胞亚群和细胞因子的变化

目的 分析柴胡解毒汤联合阿德福韦酯片治疗慢性乙型肝炎（CHB）患者体内病毒水平与外周血淋巴细胞亚群和细胞因子的变化的关系,为临床治疗CHB患者提供新的思路。方法 2013年12月至2015年3月间我院收治的CHB患者60例,被分为A组、B组和C组。给予A组服用柴胡解毒汤治疗,给予B组服用阿德福韦酯片,C组在B组基础上,服用柴胡解毒汤治疗。3组均观察12 m。采用ELISA法检测血清HBV标记物和血清IL-2水平,采用荧光定量PCR法检测血清HBV DNA水平,使用贝克曼库尔特流式细胞仪检测T细胞亚群和自然杀伤细胞百分比。结果 在治疗12 m末,C组患者HBV DNA阴转率、ALT复常率和HBeAg阴转率分别为85.00%、80.00%和80.00%,均显著高于A组（分别为50.00%、65.00%和45.00%）或B组（分别为65.00%、55.00%和50.00%,P<0.05）;C组患者外周血CD3⁺T细胞、CD4⁺T细胞和CD4⁺/CD8⁺细胞比值分别为（65.2±9.6）%、（28.4±7.2）%和（1.1±0.3）,与A组【分别为（57.5±8.7）%、（45.7±5.4）%和（1.8±0.6）】或B组【（55.7±6.3）%、（23.2±9.5）%和（0.9±0.1）】比,差异显著（P<0.05）;C组患者外周血CD8⁺T细胞为（25.3±4.1）%,显著低于B组（28.7±4.3)%, P<0.05];C组患者外周血NK细胞与A组或B组比,无显著性差异（P>0.05）,但血清IL-2水平【（3.6±0.8） ng/mL】显著高于B组【（2.8±0.5） ng/mL,P<0.05】;A组CD4⁺T细胞增加与HBV DNA载量减少呈显著正相关（P<0.05）;C组CD3⁺T细胞增加、CD8⁺T细胞减少、NK细胞增加与HBV DNA载量减少呈正相关（P<0.05）。结论 柴胡解毒汤联合阿德福韦酯片治疗慢性乙型肝炎患者可调节外周血淋巴细胞比例失调,打破免疫耐受,恢复肝功能,提高抗病毒效果。

Changes of peripheral blood T lymphocyte subsets and IL-2 in patients with chronic hepatitis B receiving Bupleurum Jiedu decoction combined with adefovir dipivoxil therapy

Objectives To investigate the changes of peripheral blood T lymphocyte subsets and IL-2 in patients with chronic hepatitis B（CHB） receiving Bupleurum Jiedu decoction combined with adefovir dipivoxil （ADV） therapy. Methods 60 patients with CHB were recruited in our hospital between December 2013 and March 2015. They were treated with Bupleurum Jiedu decoction in group A （n=20）,with ADV in group B （n=20） and with both in group C（n=20）. All regimens lasted for 12 months. Serum HBV markers and IL-2 were detected by ELISA,and T lymphocyte subsets and natural killer cells were detected by flow cytometry. Results At the end of 12-month treatment,the serum HBV DNA loss,ALT normalization rate and HBeAg negative rate in group C were 85.00%,80.00% and 80.00%,much higher than in group A（50.00%,65.00% and 45.00%,respectively） or in group B（65.00%,55.00% and 50.00%,respectively,P<0.05）;the proportion of peripheral CD3⁺T cells and CD4⁺T cells and ratio of CD4⁺/CD8⁺ cells in groups C were（65.2±9.6）%,（28.4±7.2）% and（1.1±0.3）,significantly different as compared to those in group A 【（57.5±8.7）%,（45.7±5.4）% and（1.8±0.6）, respectively or group B（55.7±6.3）%,（23.2±9.5）% and（0.9±0.1）,respectively,P<0.05];the proportion of CD8⁺T cells in group C was （25.3±4.1）%,much lower than in group B （28.7±4.3） %,P<0.05];the proportion of NK cells in group C was not significantly different as compared to that in group A or in group B（P>0.05）,while serum IL-2 level【（3.6±0.8）ng/mL】 was much higher than in group B【（2.8±0.5）ng/mL,P<0.05】;the increased CD4⁺T cells was positively correlated to serum HBV DNA loss in group A（P<0.05） and the increased CD3⁺T cells, decreased CD8⁺T cells and increased NK cells were positively correlated to serum HBV DNA loss in group C（P<0.05）. Conclusions The application of Bupleurum Jiedu decoction combined with adefovir dipivoxil can adjust lymphocyte dysfunction,break immune tolerance and improve the recovery of liver functions.