摘要
目的探讨外周血中干扰素调节因子8(interferon regulatory factor,IRF8)基因甲基化水平与慢性乙型肝炎(chronic hepatitis B,CHB)患者肝纤维化程度的相关性。方法选择2018年3月至2021年3月在山东省立第三医院住院治疗的236例CHB患者作为研究对象。参照《慢性乙型肝炎防治指南(2015年版)》进行肝纤维化分期,以S2、S3、S4期患者为明显肝纤维化组,S0-1期患者为不明显肝纤维化组。收集所有患者的临床指标,检测外周血IRF8基因启动子区CpG岛(共14个CpG位点)甲基化水平及IRF8 mRNA的表达水平并进行组间比较。结果不明显肝纤维化组患者107例,明显肝纤维化组患者129例。两组患者年龄、性别、体重指数和总胆红素水平比较差异无显著性(P>0.05);明显肝纤维化组白细胞计数和血小板计数显著低于不明显肝纤维化组,谷丙转氨酶、谷草转氨酶水平、天冬氨酸转氨酶/血小板比率指数和FIB-4指数显著高于不明显肝纤维化组,差异均有显著性(P<0.05)。在14个CpG位点中,明显肝纤维化组的CpG 2、CpG 6、CpG 9和CpG 13位点甲基化水平高于不明显肝纤维化组(P<0.05);明显肝纤维化组IRF8基因的总甲基化水平为2.24%±0.19%,显著高于不明显肝纤维化组(1.87%±0.16%),差异有显著性(P<0.001)。受试者工作特征曲线分析显示,应用IRF8甲基化水平诊断明显肝纤维化的曲线下面积为0.909(95%CI 0.873~0.945),敏感度为83.7%,特异度为86.0%。明显肝纤维化组IRF8mRNA表达水平为1.47±0.11,低于不明显肝纤维化组(1.82±0.14),差异有显著性(P<0.001)。Pearson相关分析结果显示,CHB患者的IRF8 mRNA表达水平与甲基化水平呈显著负相关(P<0.001)。结论外周血IRF8基因甲基化水平与CHB患者肝纤维化程度具有显著相关性,可作为肝纤维化进展的生物标志物,在肝纤维化的无创诊断中具有一定应用价值。
Objective This study was conducted to investigate the association between interferon regulatory factor(IRF8)in peripheral blood and the degree of liver fibrosis in patients with chronic hepatitis B(CHB).Method A total of 236 CHB patients treated and hospitalized in The Third Hospital of Shandong Province from March 2018 to March 2021 were selected as the research subjects.The stages of liver fibrosis were divided into S0-1,S2,S3 and S4 according to the diagnostic criteria in Guidelines for the Prevention and Treatment of Chronic Hepatitis B(2015 edition).Stages≥S2 were defined as obvious liver fibrosis,and S0-1 was defined as no obvious liver fibrosis.Clinical indicators were collected to detect the methylation level and mRNA level of the CpG island(a total of 14 CpG sites)in the IRF8 gene promoter region of patients.Result There were 107 patients in the non-obvious liver fibrosis group(STAGE S0-1)and 129 patients in the obvious liver fibrosis group(stage S2-4).There were no significant differences in age,gender,BMI and TB levels between non-obvious and obvious hepatic fibrosis groups(P>0.05).The levels of WBC and PLT in the obvious fibrosis group were significantly lower than those in the non-obvious fibrosis group,while the levels of ALT,AST,APRI and FIB-4 were significantly higher than those in the non-obvious fibrosis group(P<0.05).Among the 14 CpG sites,CpG 2,CpG 6,CpG 9 and CpG 13 sites in the obvious liver fibrosis group were significantly hypermethylated compared with those in the non-obvious liver fibrosis group(P<0.05).The total methylation level of IRF8 gene in the obvious hepatic fibrosis group was 2.24%±0.19%,which was significantly higher than that in the non-obvious hepatic fibrosis group(1.87%±0.16%,P<0.001).The results of subject operating characteristic curve analysis showed that the area under the curve of IRF8 methylation level for the diagnosis of obvious liver fibrosis was 0.909(95%CI 0.873~0.945),with a sensitivity of 83.7%and specificity of 86.0%.The mRNA expression level of IRF8 gene
作者
宋佳
刘伟伟
张翠翠
刘昌琳
杨佳佳
Song Jia;Liu Weiwei;Zhang Cuicui;Liu Changlin;Yang Jiajia(Department of Hepatobiliary Surgery,Third Hospital of Shandong Province,Shandong Jinan 250031,China;Department of Infection Management,Suzhou Hospital Affiliated to Nanjing Medical University,Jiangsu Suzhou 215008,China)
出处
《中国医刊》
CAS
2022年第3期263-267,共5页
Chinese Journal of Medicine
基金
南京医科大学科技发展基金(NMUB2020259)。
