HBeAg阳性慢性乙型肝炎患者血清Mig、RANTES和IL-9水平与HBV前C/BCP区变异的关系及其对聚乙二醇琢-干扰素治疗应答的影响

Correlation of serum Mig, RANTES and IL-9 levels to HBV pre-C/BCP mutation and their influences on the response to Peg-IFN-α therapy in patients with HBeAg-positive hepatitis B

目的研究HBeAg阳性CHB患者血清干扰素-γ诱导的单核因子(Mig)、调节活化正常T细胞表达和分泌的趋化因子(RANTES)和IL-9水平与HBV前C区和BCP区变异之间关系及其对聚乙二醇α-干扰素治疗应答的影响。方法纳入43例接受聚乙二醇α-干扰素治疗的HBeAg阳性CHB患者,采用PCR技术扩增治疗前患者血清HBV前C区和BCP区基因片段,并测序分析。采用微量样本多指标流式蛋白定量(CBA)技术检测血清Mig、RANTES和IL-9水平。结果在43例HBeAg阳性CHB患者中,检测到HBV前C区和(或)BCP区野生型(WT)24例(55.8%)和突变型(MT)19例(44.2%);野生组血清RANTES和IL-9基线水平分别为(3274.24±814.79)pg/mL和(9.40±0.89)pg/mL,突变组则为(2742.40±764.24)pg/mL和(10.78±2.73)pg/mL,两组间差异均具有统计学意义(P<0.05);在治疗48 w时,突变组患者获得CR者9例(47.4%),野生组患者4例(16.7%),两组间差异有统计学意义(P<0.05);突变组和野生组对聚乙二醇α-干扰素治疗实现完全应答的CHB患者IL-9、Mig和RANTES基线水平均无显著性差异;突变组中治疗24 w时HBsAg下降幅度>1 log10的CHB患者血清Mig基线水平为(138.17±96.57)pg/mL,而HBsAg下降<1 log10的CHB患者为(89.74±78.25)pg/mL,两组间差异有统计学意义(P<0.05);聚乙二醇α-干扰素治疗过程中,突变组血清IL-9基线水平为(10.78±2.73)pg/mL,治疗12 w和24 w时分别为(8.83±1.94)pg/mL和(8.91±1.97)pg/mL,均明显低于基线水平(P<0.05),而野生组中未发现有类似的变化。结论 HBV前C或(和)BCP区变异与IL-9水平升高密切相关,但是IL-9水平与聚乙二醇α-干扰素抗病毒的疗效无关。Mig基线高水平可能有利于突变组CHB患者在聚乙二醇α-干扰素治疗过程中实现HBsAg的清除。

Objective To study the correlation of serum monokine induced by IFN-γ （Mig）,regulated upon activation normal T-cell expressed and secreted factors （RANTES） and IL-9 levels to HBV pre-C /BCP mutation and their influences on the response to Peg-IFN-α therapy in patients with HBeAg-positive hepatitis B. Methods A total of 43 HBeAg positive patients with CHB who received Peg-IFN-α therapy were enrolled in this study. Serum HBV DNA was extracted from peripheral blood,and polymerase chain reaction （PCR） was performed to sequence the Pre-C/BCP gene fragments. Serum levels of Mig,RANTES and IL-9 were detected by using cytometric bead array （CBA）. Results The mutation （MT） of HBV Pre- C and/or BCP was positive in 19 （44.2%） patients,and the wild type was 24（55.8%） out of the 43 HBeAg-positive hepatitis B patients; the serum levels of RANTES and IL-9 were （3274.24±814.79） pg/mL and（9.40±0.89） pg/mL, respectively, in patients with HBV pre-C/BCP mutation, and were （2742.40±764.24） pg/mL and （10.78±2.73） pg/mL, respectively, in patients without HBV pre-C/BCP mutation,and the difference was statistically significant （P〈0.05）;nine （47.4%） out of patients with and 4 （16.7%） out of those without viral mutation obtained complete response at the end of 48 week regimen （P〈0.05）. The baseline level of serum Mig in patients with serum HBsAg decline at week 24 of Peg-IFN-α treatment was （138.17±96.57） pg/mL,and the baseline level in those without HBsAg decline was （89.74±78.25） pg/mL （P〈0.05）;In patients with HBV pre-C/BCP mutation, the baseline level of IL-9 was （10.78±2.73） pg/mL,the levels at week 12 and 24 during the treatment were （8.83±1.94） pg/mL and （8.91±1.97） pg/mL,both significantly lower than the baseline （P〈0.05）. Conclusion Serum level of IL-9 is closely associated with HBV Pre-C / BCP mutation,but not with anti-HBV efficacy of Peg-IFN-α treatment in HbeAg- positive patients with CHB. Higher baseline level of Mig could contribute to HBsAg decline after PeglFN-α therapy in CHB patients with HBV pre-C/BCP mutation.