慢性乙型肝炎HBeAg阳性者干扰素γ诱导单核细胞因子、白细胞介素9与乙型肝炎病毒前C/BCP区变异相关性及其对干扰素治疗的意义

Correlation of serum monokine induced by IFN-γand interleukin9 to HBV pre-C/BCP mutation and their influences on the response to interferon therapy in patients with HBeAg-positive chronic hepatitis B

目的分析慢性乙型肝炎(chronic hepatitis B,CHB)HBeAg阳性患者血清干扰素γ诱导单核细胞因子(monokine induced by IFN-γ,Mig)、白细胞介素(interle-ukin,IL)-9与乙型肝炎病毒(hepatitis B Virus,HBV)前C/BCP区变异的相关性以及其对干扰素疗效影响。方法回顾性分析2015年2月至2018年2月四川省简阳市人民医院收治的110例CHB且HBeAg阳性患者资料,均给予聚乙二醇α-干扰素抗病毒治疗;治疗前扩增患者血清HBV前C/BCP区的基因片段并将患者分成HBV前C/BCP区野生型组(野生组61例)及突变型组(突变组49例),并比较两组患者血清Mig、IL-9情况以及抗病毒治疗疗效差异。结果突变组治疗前患者血清IL-9[(10.8±1.9)ng/L]明显高于野生组[(8.3±1.7)ng/L](P<0.05)。突变组治疗48周后获得完全应答率[46.9%(23/49)]显著高于野生组[16.4%(10/61)]χ^2=7.083,P=0.018;突变组治疗24周后HBsAg下降>1 lg10者较下降≤1 lg10者治疗前的血清Mig显著升高[(129.2±37.9)ng/L与(91.5±25.7)ng/L](P<0.05)。突变组治疗12、24周血清IL-9分别为(8.8±1.9)、(8.9±1.6)ng/L,均较治疗前显著降低(P均<0.05)。结论CHB且HBeAg阳性患者治疗前血清IL-9的高表达与HBV前C/BCP区的变异关系密切,IL-9的表达与干扰素抗病毒疗效无相关性;患者治疗前Mig的高表达可能对HBV前C/BCP区变异者干扰素抗病毒疗效更有利。

Objective To study the correlation of serum monokine induced by IFN-γ(Mig)and interleukin9(IL-9)levels to HBV pre-C/BCP mutation and their influences on the response to interferon therapy in patients with HBeAg-positive chronic hepatitis B(CHB).Methods A total of 110 cases of HBeAg-positive CHB patients in the People′s Hospital of Jianyang City were retrospectively analyzed from February 2015 to February 2018,and all received pegylated-IFN-αtherapy.Before treatment,the gene fragment of HBV pre-C/BCP region was amplified and the patients were divided into two groups:wild type group(61 cases)and mutant group(49 cases).The difference of serum MIG,IL-9 and antiviral treatment effect between the two groups were compared.Results The serum IL-9 of mutant group before treatment((10.8±1.9)ng/L)was significantly higher than that of wild group((8.3±1.7)ng/L)(P<0.05).The complete response rate of mutation group was 46.9%(23/49)after 48 weeks of treatment,which was significantly higher than that of wild group(16.4%(10/61))(χ^2=7.083,P=0.018).After 24 weeks of treatment,the serum Mig of patients with HBsAg decrease>1 lg 10 in mutation group before treatment was significantly higher than HBsAg decrease≤1 lg 10((129.2±37.9)ng/L vs.(91.5±25.7)ng/L)(P<0.05).The serum IL-9 in the mutant group were(8.8±1.9)ng/L and(8.9±1.6)ng/L at 12 and 24 weeks after treatment respectively,which were significantly lower than that before treatment(all P<0.05).Conclusion The high expression of IL-9 in serum of CHB and HBeAg positive patients before treatment is closely related to the variation of HBV pre-C/BCP region,and the expression of IL-9 is not related to the antiviral effect of interferon.The high expression of MIG in patients before treatment may be more beneficial to the antiviral effect of interferon in patients with HBV pre-C/BCP region variation.