阿德福韦酯对慢性乙型肝炎患者外周血IFN-γ和IL-18的影响

Effects of adefovir dipivoxil on serum IFN-γ and IL-18 in patients with chronic hepatitis B

目的:观察阿德福韦酯治疗前后慢性乙型肝炎患者外周血干扰素-γ(IFN-γ)和白细胞介素-18(IL-18)的变化,探讨阿德福韦酯抗乙型肝炎病毒(HBV)的免疫效应机制。方法:选择参加阿德福韦酯Ⅱ期临床试验的42例慢性乙型肝炎患者作为研究对象,检测阿德福韦酯治疗前、治疗4、12、24、48周末患者血清IFN-γ和IL-18水平,以及HBV DNA及ALT水平变化。结果:治疗前患者IFN-γ及IL-18水平明显高于正常对照组(P<0.01)。治疗后,HBV DNA水平逐渐降低,各检测时间点之间比较差异均有统计学意义(P<0.01),ALT在治疗4周时较治疗前有所升高(P<0.05),然后逐渐下降直至正常。IFN-γ及IL-18水平逐渐升高,在12周时达到高峰(P<0.01),然后逐渐降低。完全应答组治疗前INF-γ和IL-18水平高于部分应答组和无应答组(P<0.01)。完全应答和部分应答组治疗后INF-γ和IL-18水平与治疗前比较均明显升高(P<0.01),而无应答组IFN-γ和IL-18治疗前后比较,差异无显著性意义(P>0.05)。结论:阿德福韦酯除直接抑制病毒复制外,可促进Th1型细胞因子分泌,调动机体对HBV的细胞免疫,有利于HBV的清除。

Objective： To study the dynamic changes of IFN-γ and IL-18 in the serum of patients with chronic hepatitis B （CHB） treated with adefovir dipivoxil. Methods： Forty-two CHB patients （35 men and 7 women） were enrolled phase Ⅱ clinical trial of adefovir dipivoxil. At different time （ before therapy, and 4 weeks, 12 weeks, 24 weeks, 48 weeks after therapy）, the serum level of IFN-γ and IL-18 of each patient were determined by specific-ELISA, and serum HBV DNA and ALT were also quantified by real-time fluorescent PCR and biochemical methods respectively. Results： The levels of IFN-γ and IL- l8 of patients with CHB were significantly higher than normal controls before therapy （P 〈 0.01 ）. The levels of HBV DNA of patients decreased gradually after treatment with adefovir dipivoxil, but the levels of ALT increased at 4 weeks, and then decrease to normal value after therapy. The levels of IFN-γ and IL-18 increased and reached to peak at 12 weeks after therapy, and then decreased gradually. The levels of IFN-γ and IL-18 of patients in response group were significantly higher than that of non-response group before＇and after therapy （P 〈0. 01 ）. Conclusion： It is suggested that the cell immunity against HBV of patients with CHB can be enhanced by adefovir dipivoxil, which could benefit for elimination of HBV.