阿德福韦酯对慢性乙型肝炎患者外周血干扰素和白细胞介素的影响

Effects of adefovir dipivoxil on serum IFN-γ and IL-4 in patients with chronic hepatitis

目的观察阿德福韦酯治疗前后慢性乙型肝炎(CHB)患者外周血干扰素(IFN)-γ和白细胞介素(IL)-4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108例CHB患者纳入随机、双盲、对照和多中心阿德福韦酯Ⅲ期临床试验,用双抗体夹心ELISA法检测阿德福韦酯治疗前、治疗4、12、24、48周末患者血清中IFN-γ和IL-4水平,采用实时荧光聚合酶链反应(PCR)同时检测相应时间点的血清HBVDNA。结果CHB患者转氨酶在治疗24周末达正常范围,并持续至治疗结束;HBVDNA在4周末明显低于治疗前(P<0.05),并持续下降至治疗结束;IFN-γ和IL-4水平逐渐上升,在24周末及48周末与治疗前相比有显著差异(P<0.001)。结论阿德福韦酯抗病毒治疗后使机体免疫增强,这种作用可能是由于治疗使病毒负载下降和CD4+T淋巴细胞活性重建而出现。

Objective To study the dynamic changes of IFN-γ and IL-4 in the serum of patients with chronic hepatitis B （CHB） treated with adefovir dipivoxil. Methods One hundred and eight CHB patients（96 males and 12 femals） were enrolled in a randomized, double-blinded, controlled and multicentral Phase Ⅲ clinical trial of adefovlr 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-4 of each patient were determined by specific-ELISA, and the serum HBV-DNA level was also quantitated by real time fluorescent PCR. Results The serum level of ALT and AST improved significantly in CHB patient 12 weeks after therapy with adefovir dipivoxil（ P 〈 0.05）, and kept normal from 24 weeks after therapy to the end point of the clinical trial. The serum HBV DNA decreased significantly in 4 weeks after therapy（ P 〈 0.05） and continued to decrease till the end point. Meanwhile, the level of serum IFN-γ and IL-4 increased slowly till the end point, which was significantly higher in 24 weeks and 48 weeks of therapy than that of pretherapy（ P 〈 0.001 ）. Conclusion The immunity of patients with CHB can be enhanced by adefovir dipivoxil, which may result from the reduction of viral load and restoration of CD4^＋ T cell reactivity.