药物性肝损伤伴自身免疫现象患者血清γ干扰素诱导蛋白10水平及其单核苷酸多态性  

Serum interferon-gamma-induced protein-10 level and gene polymorphism in patients with drug-induced liver injury accompanied by autoimmune phenomena

作　　者：任姗[1] 杜晓菲[1] 黄云丽[1] 黄春洋[1] 张晓丹[1] 单晶[1] 陈新月[1] REN Shan;DU Xiaofei;HUANG Yunli(Department of Hepatology and Immunology,Beijing YouAn Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院肝病免疫科,北京100069

出　　处：《临床肝胆病杂志》2020年第3期602-607,共6页Journal of Clinical Hepatology

基　　金：北京市属医院科研培育计划项目(PX2017022);首都医科大学重点实验室开放研究课题(2-03-02-BJYAH2016002),“十三五”国家科技重大专项课题(2017ZX10202201,2017ZX10201021-001-008);佑安肝病艾滋病基金科研课题(YNKTQN20180209)。

摘　　要：目的探讨药物性肝损伤伴自身免疫现象(AI-DILI)患者血清γ干扰素诱导蛋白10(IP-10)单核苷酸基因多态性(SNP)及其表达水平。方法选取2016年10月-2019年6月首都医科大学附属北京佑安医院肝病免疫科诊治的药物性肝损伤(DILI)患者168例,分为AI-DILI组(n=72)与非AI-DILI组(n=96),检测IP-10 rs56061981位点SNP及血清IP-10水平。比较两组间IP-10水平及SNP的差异性,并与AI-DILI的发生进行分析。等位基因频率直接由基因分型结果计算,采用χ2检验进行Hardy-Weinberg平衡分析。计量资料2组间比较采用t检验和Mann-Whitney U检验,不同时间点比较采用重复测量资料方差分析;计数资料采用χ2检验或Fisher’s确切概率法。相关性分析采用pearson法。采用受试者工作特征曲线(ROC曲线)分析基线IP-10水平对AI-DILI的预测作用。结果AI-DILI组自身抗体阳性率为91.67%,非AI-DILI组自身抗体阳性率为12.5%,差异有统计学意义(χ2=103.8,P<0.05)。AI-DILI组CC基因型频率显著高于非AI-DILI组(77.78%vs 62.50%,χ2=4.592,P=0.03),同时AI-DILI组携带C等位基因频率显著高于非AI-DILI组(86.11%vs 72.92%,χ2=4.41,P=0.04)。AI-DILI患者基线IP-10水平显著高于非AI-DILI患者[(627.99±198.07)pg/ml vs(378.13±218.45)pg/ml,t=7.34,P<0.05),与基线AST水平及AIH评分呈正相关(r值分别为0.67、0.79,P值均<0.05)。基线IP-10预测AI-DILI的ROC曲线下面积为0.832,敏感度、特异度分别为0.846、0.867,最佳阈值为527.03 pg/ml。CC基因型联合基线IP-10≥527.03 pg/ml预测AI-DILI发生,其阳性预测值为92.84%,阴性预测值为8.33%。结论IP-10 rs 56061981 CC基因型与AI-DILI的发生有关,并影响AI-DILI血清IP-10表达,二者联合预测AI-DILI效能显著提高。Objective To investigate the single nucleotide polymorphism(SNP)and serum expression of interferon-gamma-induced protein 10(IP-10)in patients with drug-induced liver injury accompanied by autoimmune phenomena(AI-DILI).Methods A total of 168 patients with drug-induced liver injury(DILI)who were diagnosed and treated in Beijing YouAn Hospital,Capital Medical University,from October 2016 to June 2019 were enrolled and divided into AI-DILI group(n=72)and non-AI-DILI group(n=96).The SNP of IP-10 rs56061981 locus was detected and the serum level of IP-10 was measured.The two groups were compared in terms of IP-10 level and SNP genotype,and their association with the development of AI-DILI was analyzed.Allele frequency was calculated based on genotype results,and the chi-square test was used for Hardy-Weinberg equilibrium analysis.The t-test and the Mann-Whitney U test were used for comparison between two groups;a repeated measures analysis of variance was used for comparison between different time points;the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups.The Pearson correlation analysis was used to investigate correlation.The receiver operating characteristic(ROC)curve was used to analyze the value of baseline IP-10 level in predicting AI-DILI.Results There was a significant difference in the positive rate of autoantibody between the AI-DILI group and the non-AI-DILI group(91.67%vs 12.5%,χ2=103.8,P<0.05).Compared with the non-AI-DILI group,the AI-DILI group had significantly higher distribution frequency of CC genotype(77.78%vs 62.50%,χ2=4.592,P=0.03)and frequency of C allele(86.11%vs 72.92%,χ2=4.41,P=0.04).The AI-DILI group had a significantly higher baseline IL-10 level than the non-AI-DILI group(627.99±198.07 pg/ml vs 378.13±218.45 pg/ml,t=7.34,P<0.05),and baseline IL-10 level was positively correlated with baseline aspartate aminotransferase level and AIH score(r=0.67 and 0.79,both P<0.05).At the optimal cut-off value of 527.03 pg/ml,baseline IP-10 level

关 键 词：药物性肝损伤 肝炎 自身免疫 多态性 单核苷酸 γ干扰素诱导蛋白-10 

分 类 号：R575[医药卫生—消化系统]