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α-干扰素治疗应答的影响*

doi:10.3969/j.issn.1672-5069.2016.03.008

摘要/Abstract

摘要： 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。

关键词: 慢性乙型肝炎, 病毒变异, 聚乙二醇α-干扰素, 白细胞介素-9, 干扰素-γ诱导单核因子

Abstract: 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 PegIFN-α therapy in CHB patients with HBV pre-C/BCP mutation.

Key words: Hepatitis B, Mutation, PEG-IFN-α, Interleukin 9, Monokine induced by IFN-γ

单奔，孔歌，李彦，王霞，傅涓涓，李丽，潘修成. 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α-干扰素治疗应答的影响*[J]. 实用肝脏病杂志, 2016, 19(3): 283-287.

Shan Ben,Kong Ge,Li Yan,et al.. 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[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(3): 283-287.

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