乙型肝炎e抗原阳性慢性乙型肝炎患者在替比夫定治疗期间外周血Th1/Th2型细胞因子水平的动态变化情况

目的 探讨乙型肝炎e抗原(HBeAg)阳性的慢性乙型肝炎(CHB)患者在用替比夫定(LDT)治疗期间Th1/Th2型细胞因子水平的动态变化情况及其与治疗转归的关系.方法 收集接受LDT治疗的15例HBeAg阳性CHB患者在基线与治疗4、8、12、24、48周时的外周血,用流式细胞仪对其血清白细胞介素(IL)-2、-4、-6、-10,以及肿瘤坏死因子(TNF)α与干扰素(IFN)γ的表达水平进行动态检测;比较完全应答组,部分应答组、无应答组、病毒学突破组及各组在不同治疗时间点的Th1/Th2型细胞因子水平.对数据的统计学分析用重复测量设计方差分析与Spearman相关分析. 结果完全应答组的Th1型细胞因子水平高于部分应答组、无应答组及治疗中病毒学突破组;而Th2型细胞因子水平则低于其他各组,但各组之间的差异无统计学意义(P>0.05).在完全应答组内IL-2、TNF α及IFN γ水平自服用LDT 12周起及其后各时间点较基线时明显升高,差异具有统计学意义(P<0.05);部分应答组内从服药24周起IFN γ水平较基线时升高(P<0.05);无应答组在服药48周时IL-6及IL-10水平较基线时明显升高(P<0.05);在病毒学突破组自服药24周起的IL-4水平及服药12周起的IL-6水平与基线相比,逐渐升高,且差异具有统计学意义(P<0.05).结论 Th1/Th2型细胞因子的活性平衡与LDT治疗HBeAg阳性CHB患者的转归有一定相关性,这可能与LDT治疗对CHB患者的免疫应答有一定程度的恢复作用有关.

Dynamic changes of Th1/Th2 type cytokines in peripheral blood of patients with hepatitis B e antigen-positive chronic hepatitis B treated with telbivudine

Objective To investigate the dynamic changes of Th1/Th2 type cytokines in peripheral blood of patients with hepatitis B e antigen-positive chronic hepatitis B treated with telbivudine (LDT). Methods The levels of IL-2, IL-4, IL-6, IL-10, TNF alpha, IFN gamma in the blood cells of HBeAg positive chronic hepatitis B patients were measured at 0, 4, 8, 12, 24, 48 weeks after LDT treatment by fluorescence activated cell sorting (FACS), the levels and dynamic changes of Th1/Th2 type cytokines in groups of com-plete response, partial response, non-response, virologic breakthrough were compared. Results The levels of Th1 type cytokines in complete response group were higher than those in groups of partial response, non-response and virologic breakthrough, however, the levels of Th2 type cytokines showed an opposite trend compared with Th1 type cytokines. There were no significant difference between each group.In complete response group, the levels of IL-2, TNF alpha and IFN gamma were higher than baseline 12 weeks after LDT treatment (P<0.05). In partial response group the level of IFN gamma was higher than baseline 24weeks after LDT treatment (P<0.05). In non-response group, the levels of IL-6 and IL-10 were higher than baseline at 48 weeks after LDT treatment (P<0.05). In virologic breakthrough group, the level of IL-4 was higher than baseline 24 weeks after LDT treatment (P<0.05), while the level of IL-6 was higher than baseline 12 weeks after LDT treatment (P<0.05). Conclusions The balance of Th1/Th2 type cytokines plays an important role in the outcome of patients with hepatitis B e antigen-positive chronic hepatitis B treated with LDT. The immune response of patients with chronic hepatitis B is improved to some extent after LDT therapy.