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interleukin 28B genetic polymorphism and hepatitis B virus infection 被引量:5
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作者 Toru Takahashi 《World Journal of Gastroenterology》 SCIE CAS 2014年第34期12026-12030,共5页
Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-&#x003b1; (PEG-IFN) plus ri... Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-&#x003b1; (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B. 展开更多
关键词 interleukin 28B POLYMORPHISM Hepatitis B virus INTERFERON Pegylated interferon
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Ⅰ型自身免疫性肝炎患者IL28RA、PD-L1表达及与肝功能的相关性分析
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作者 陈杰 周长雄 +1 位作者 龚秀敏 郭治 《中国现代医学杂志》 CAS 2024年第12期78-83,共6页
目的 分析Ⅰ型自身免疫性肝炎(AIH)患者白细胞介素-28受体拮抗剂(IL28RA)、程序性细胞死亡因子配体1(PD-L1)表达及与肝功能的关系。方法 选取2018年2月—2023年3月仙桃市第一人民医院收治的Ⅰ型AIH患者85例,其中活动期53例(重度炎症组8... 目的 分析Ⅰ型自身免疫性肝炎(AIH)患者白细胞介素-28受体拮抗剂(IL28RA)、程序性细胞死亡因子配体1(PD-L1)表达及与肝功能的关系。方法 选取2018年2月—2023年3月仙桃市第一人民医院收治的Ⅰ型AIH患者85例,其中活动期53例(重度炎症组8例、中度炎症组12例和轻度炎症组33例)、缓解期32例。在超声引导下通过BARD一次性全自动活检枪实施肝穿刺活检术取得肝组织,另取同期该院收治的27例肝血管瘤患者(经手术取得肝组织)为对照组。采用ABC法测定肝组织PD-L1蛋白含量,荧光实时荧光定量聚合酶链反应检测肝组织IL28RA基因表达,比较肝功能指标[γ-谷氨酰转肽酶(γ-GT)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]水平及肝组织IL28RA、PD-L1表达,分析肝组织IL28RA、PD-L1表达与肝功能指标的相关性。结果 活动期患者IL28RA相对表达量低于缓解期患者(P <0.05),PD-L1高于缓解期患者(P <0.05)。活动期患者TBIL、AST、γ-GT、ALT水平均高于缓解期患者(P <0.05)。AIH组IL28RA基因相对表达量低于对照组(P <0.05),PD-L1蛋白含量高于对照组(P <0.05)。与缓解期患者相比,各炎症组IL28RA基因相对表达量降低(P <0.05),PD-L1、AST、ALT、TBIL、γ-GT、IgG水平均升高(P <0.05)。Ⅰ型AIH患者IL28RA表达与AST、ALT、TBIL均呈负相关(r=-0.567、-0.671和-0.549,均P=0.000);PD-L1表达与AST、ALT、TBIL、血清IgG均呈正相关(r=0.643、0.598、0.552和0.476,均P=0.000)。结论 Ⅰ型AIH患者与IL28RA、PD-L1表达及与肝功能密切相关。Ⅰ型AIH患者IL28RA表达下调,PD-L1表达上调。IL28RA表达与肝功能、肝组织炎症活动度呈负相关,PD-L1表达与肝功能、肝组织炎症活动度及血清IgG水平呈正相关。 展开更多
关键词 自身免疫性肝炎 白细胞介素28受体拮抗剂 程序性细胞死亡因子配体1 肝功能
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Relationship between the genetic variation in interleukin 28B and response to antiviral therapy in patients with chronic hepatitis C 被引量:2
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作者 XIE Jun-qiang GUO Xiao-yan +5 位作者 ZHANG Xiao-hong LIN Bing-liang XIE Dong-ying GAO Zhi-liang WANG Gen-shu ZHAO Zhi-xin 《Chinese Medical Journal》 SCIE CAS CSCD 2012年第13期2334-2338,共5页
Background Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the... Background Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-a plus ribavirin (PEG-IFN-a/RBV) treatment. Methods To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-a/RBV therapy. Results The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P 〈0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR=10.95, 95% CI =4.12-29.11, P=1.5×10-7 and OR=3.93, 95% CI =1.86-8.32, P=-2.1×10-4 respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P 〈0.001). Conclusions The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression. 展开更多
关键词 hepatitis C virus interleukin 28B genetic variation sustained virological response RELAPSE
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Impact of Interleukin-28B Polymorphism on Response to Treatment in Chinese Hepatitis C Patients 被引量:2
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作者 Lü Jian-nan1, WANG Song2, XU Yan1, ZHANG Man-hua1, SIQING Tunala1, JI Shang-wei1, JIAO Jian1, WANG Xu1 and WANG Jiang-bin1 1. China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China 2. The Second Hospital of Jilin University, Changchun 130041, P. R. China 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2012年第1期79-83,共5页
The candidate polymorphism rs12979860 of interleukin 28B(IL28B) gene was genotyped by means of polymerase chain reaction(PCR) amplification and direct PCR sequencing, and then the role of this single nucleotide po... The candidate polymorphism rs12979860 of interleukin 28B(IL28B) gene was genotyped by means of polymerase chain reaction(PCR) amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism(SNP) in the response to the treatment of 172 Chinese patients with hepatitis C virus(HCV) chronic infection was analyzed. The results show that the frequencies of major homozygotes(CC) and heterozygotes(CT) of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes(TT) wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response(SVR) in HCV geno type 1 infected patients(P〈0.001) but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response(RVR) in both HCV genotype 1 infected patients(P〈0.001) and non-genotype 1 infected patients(P〈0.001). Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C(CHC) patients. 展开更多
关键词 Hepatitis C virus(HCV) interleukin 28B(IL28B) interleukin-28B GENE
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重组鼠IL-28的原核表达、纯化及多克隆抗体的制备 被引量:3
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作者 袁利学 刘洋 +2 位作者 步雪峰 郑金旭 严玉兰 《江苏大学学报(医学版)》 CAS 2009年第6期472-474,479,共4页
目的:获取重组鼠IL-28(m IL-28)纯化蛋白,制备多克隆抗体。方法:用PCR技术扩增鼠IL-28成熟蛋白的编码序列,克隆入原核表达载体pET-30,构建融合表达载体pET-30 a-m IL-28,转化大肠埃希菌BL21(DE3),以IPTG诱导表达IL-28融合蛋白,经... 目的:获取重组鼠IL-28(m IL-28)纯化蛋白,制备多克隆抗体。方法:用PCR技术扩增鼠IL-28成熟蛋白的编码序列,克隆入原核表达载体pET-30,构建融合表达载体pET-30 a-m IL-28,转化大肠埃希菌BL21(DE3),以IPTG诱导表达IL-28融合蛋白,经镍柱亲和层析纯化,然后免疫6-8周龄鸡,制备多克隆抗体,采用ELISA检测抗体效价。结果:成功构建了表达载体pET-30 a-m IL-28,DNA序列测定结果与预期结果一致。在37℃培养条件下,IPTG诱导表达的IL-28融合蛋白进行SDS-PAGE电泳分析,发现其与融合蛋白的理论计算值一致,免疫鸡后收获抗血清,ELISA显示抗体效价具有高度特异性。结论:获得了重组鼠IL-28纯化蛋白,制备了鼠IL-28多克隆抗体,为进一步深入研究IL-28的生物活性及其应用打下基础。 展开更多
关键词 白细胞介素-28 大肠埃希菌 蛋白质纯化 抗体制备
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IL-28B基因多态性对干扰素治疗丙型病毒性肝炎应答的影响 被引量:8
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作者 佟小非 尤红 《首都医科大学学报》 CAS 2012年第3期334-337,共4页
目前针对丙型肝炎的标准治疗方案是聚乙二醇干扰素联合利巴韦林。宿主IL-28B基因多态性对丙型病毒性肝炎干扰素治疗清除有影响,可以对治疗应答进行预测。本文将从IL-28B基因多态性与慢性丙型肝炎治疗应答的关系及其影响应答的可能机制... 目前针对丙型肝炎的标准治疗方案是聚乙二醇干扰素联合利巴韦林。宿主IL-28B基因多态性对丙型病毒性肝炎干扰素治疗清除有影响,可以对治疗应答进行预测。本文将从IL-28B基因多态性与慢性丙型肝炎治疗应答的关系及其影响应答的可能机制两个方面,对宿主IL-28B基因在慢性丙型肝炎治疗实践中的意义进行探讨。 展开更多
关键词 丙型病毒性肝炎 全基因组关联分析 白细胞介素28B 干扰素-λ 干扰素-Α
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蛋白酶激活受体激活对A549细胞IL-28和IL-29 mRNA表达的影响 被引量:2
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作者 张慧云 王海燕 +1 位作者 马文静 何韶衡 《免疫学杂志》 CAS CSCD 北大核心 2010年第10期833-837,841,共6页
目的用蛋白酶和蛋白酶激活受体激动肽(PAR-AP)刺激A549细胞后检测细胞中白细胞介素IL-28和IL-29 mRNA表达情况以分析蛋白酶激活受体激活对人肺上皮细胞IL-28和IL-29基因表达的影响。方法用最佳工作浓度的凝血酶、胰蛋白酶、类胰蛋白酶... 目的用蛋白酶和蛋白酶激活受体激动肽(PAR-AP)刺激A549细胞后检测细胞中白细胞介素IL-28和IL-29 mRNA表达情况以分析蛋白酶激活受体激活对人肺上皮细胞IL-28和IL-29基因表达的影响。方法用最佳工作浓度的凝血酶、胰蛋白酶、类胰蛋白酶及蛋白酶激活受体-1,2,3,4的激动肽刺激A549细胞后,分别在第2、8、16h收集细胞,用实时定量逆转录聚合酶链式反应(q-RT-PCR)方法分析A549细胞内IL-28和IL-29 mRNA表达。结果凝血酶作用A549后,细胞内IL-29 mRNA表达增强,高达对照组9.6倍;而细胞内IL-28 mRNA表达无明显变化。胰蛋白酶作用A549细胞后,细胞内IL-29和IL-28 mRNA表达增强,分别为对照组6.1倍和4.4倍。类胰蛋白酶作用A549细胞后,细胞内IL-29和IL-28 mRNA表达增强分别高达对照组的3.1倍和2.1倍。弹性蛋白酶作用A549细胞后,细胞内IL-29 mRNA表达增强高达对照组5.1倍而IL-28 mR-NA无明显变化。PAR-1AP(SFLLR)作用后,A549细胞内IL-29 mRNA表达增强为对照组1.7倍而IL-28 mRNA表达无明显变化。PAR-2AP(SLIGKV及tc-LIGRLO)作用后,A549细胞内IL-29和IL-28 mRNA表达增强分别为对照组4.9倍和2.4倍。PAR-3AP(TFRGAP)作用后,A549细胞内IL-29和IL-28 mRNA表达无明显变化。PAR-4AP(GYPGQV)作用后A549细胞内IL-29和IL-28 mRNA表达增强高达对照组4.1倍和5.5倍。结论 A549细胞蛋白酶激活受体的激活可以上调细胞内IL-29和IL-28 mRNA表达。 展开更多
关键词 人肺上皮细胞癌A549 白细胞介素-29 白细胞介素-28 蛋白酶 蛋白酶激活受体
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产妇外周血和胎儿脐血白细胞介素28启动子甲基化差异研究
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作者 马建鸿 张元珍 +4 位作者 祝成亮 周春 王燕 陈红 李家福 《国际检验医学杂志》 CAS 2013年第2期132-133,135,共3页
目的探讨产妇外周血和胎儿脐血白细胞介素28(IL-28)启动子甲基化差异及其对IL-28表达的影响。方法采用甲基化特异性PCR(MSP)方法检测产妇外周血和胎儿脐血IL-28启动子甲基化水平的差异;分离外周血单核细胞(PBMC),比较DNA甲基化酶活性的... 目的探讨产妇外周血和胎儿脐血白细胞介素28(IL-28)启动子甲基化差异及其对IL-28表达的影响。方法采用甲基化特异性PCR(MSP)方法检测产妇外周血和胎儿脐血IL-28启动子甲基化水平的差异;分离外周血单核细胞(PBMC),比较DNA甲基化酶活性的差异;RT-PCR检测两者PBMC中IL-28mRNA的含量;采用ELISA法检测产妇外周血和胎儿脐血IL-28水平的差异。结果 IL-28启动子在胎儿脐血中均以甲基化形式存在,而在产妇外周血中为非甲基化形式;胎儿脐血PBMC细胞核甲基化酶活性升高(P<0.05);IL-28mRNA在产妇外周血PBMC中的表达水平高于胎儿脐血PBMC;胎儿脐血IL-28含量较产妇外周血低(P<0.01)。结论胎儿脐血细胞核内甲基化酶活性升高导致IL-28启动子高甲基化,进而引起IL-28的合成和分泌降低。 展开更多
关键词 胎血 白细胞介素28 甲基化
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白细胞介素-34对类风湿关节炎成纤维样滑膜细胞CCL28表达的影响 被引量:7
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作者 欧阳寻丽 李寒 +3 位作者 孙晓彤 张彦 李霞 魏晶 《中国免疫学杂志》 CAS CSCD 北大核心 2018年第2期239-242,共4页
目的:初步探讨白细胞介素-34(IL-34)对类风湿关节炎(RA)患者成纤维细胞样滑膜细胞(FLS)CC趋化因子配体28(CCL28)表达的影响。方法:选取6例RA患者关节滑膜分离并培养FLS,分别用IL-34、IL-34受体拮抗剂/IL-34、信号通路抑制剂/IL-34刺激... 目的:初步探讨白细胞介素-34(IL-34)对类风湿关节炎(RA)患者成纤维细胞样滑膜细胞(FLS)CC趋化因子配体28(CCL28)表达的影响。方法:选取6例RA患者关节滑膜分离并培养FLS,分别用IL-34、IL-34受体拮抗剂/IL-34、信号通路抑制剂/IL-34刺激。采用反转录聚合酶链式反应(RT-PCR)检测FLS CCL28 mRNA的表达;酶联免疫吸附试验(ELISA)检测细胞培养上清中CCL28水平。两组间比较采用t检验。结果:与对照组相比,IL-34刺激后FLS分泌CCL28增多(P<0.05);加入IL-34受体拮抗剂后FLS分泌CCL28水平降低(P<0.05);细胞培养体系中加入核因子-κB(NF-κB)、丝裂原活化蛋白激酶38(p38MAPK)信号通路抑制剂后,CCL28表达明显降低(P<0.05)。结论:IL-34与其受体结合可能通过激活NF-κB和p38 MAPK信号通路促进RA FLS分泌CCL28,从而参与RA的发病过程。 展开更多
关键词 类风湿关节炎 白细胞介素-34 成纤维样滑膜细胞 CC趋化因子配体28
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Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms
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作者 Srunthron Akkarathamrongsin Sunchai Payungporn +4 位作者 Vo Duy Thong Kittiyod Poovorawan Phisit Prapunwattana Yong Poovorawan Pisit Tangkijvanich 《World Journal of Gastroenterology》 SCIE CAS 2014年第30期10599-10605,共7页
AIM: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy.
关键词 Hepatitis C virus Genotype 6 interleukin28B rs12979860 Early viral kinetics
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HBsAg阳性孕产妇HBV宫内感染危险因素及其与IL-28B基因多态性的关联
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作者 张效民 王静 +2 位作者 郑开呈 刁雪晨 孟庆华 《中华医院感染学杂志》 CAS CSCD 北大核心 2024年第9期1397-1400,共4页
目的探讨乙型肝炎病毒(HBV)携带孕产妇HBV宫内感染危险因素及其与白细胞介素-28B(IL-28B)基因多态性的关联。方法选择济南市第二妇幼保健院2019年1月-2022年2月收治的620例HBsAg阳性孕产妇为研究对象,其中50例发生HBV宫内感染患者为感染... 目的探讨乙型肝炎病毒(HBV)携带孕产妇HBV宫内感染危险因素及其与白细胞介素-28B(IL-28B)基因多态性的关联。方法选择济南市第二妇幼保健院2019年1月-2022年2月收治的620例HBsAg阳性孕产妇为研究对象,其中50例发生HBV宫内感染患者为感染组,570例未发生HBV宫内感染患者为未感染组,统计两组IL-28B基因rs8099917位点多态性,分析HBV宫内感染危险因素。结果感染组GG基因型及G等位基因频率均高于未感染组(P<0.05);HBsAg阳性孕产妇HBV宫内感染的危险因素包括IL-28B基因GG基因型、G等位基因、HBV DNA>10^(6)copies/ml、肝脏B超改变及前S1蛋白阳性(P<0.05)。结论HBsAg阳性孕产妇HBV宫内感染与IL-28B基因多态性、HBV DNA水平、肝脏B超改变、前S1蛋白阳性有关。 展开更多
关键词 孕产妇 乙肝表面抗原 乙型肝炎病毒 白细胞介素28B 宫内感染 危险因素
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Individualization of chronic hepatitis C treatment according to the host characteristics 被引量:2
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作者 Nikolaos K Gatselis Kalliopi Zachou +2 位作者 Asterios Saitis Maria Samara George N Dalekos 《World Journal of Gastroenterology》 SCIE CAS 2014年第11期2839-2853,共15页
Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people worldwide.It is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of li... Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people worldwide.It is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of liver failure and transplantation.The standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been used.Besides,understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to treatment.Recent genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV infection.The present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment. 展开更多
关键词 Chronic hepatitis C Hepatitis C virus host factors interleukin 28B Inosine triphosphatase Single nucleotide polymorphism
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Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C 被引量:1
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作者 Bogna Swiatek-Koscielna Ewelina Kaluzna +8 位作者 Ewa Strauss Jerzy Nowak Iwona Bereszyńska Ewelina Gowin Jacek Wysocki Jolanta Rembowska Dominika Barcińska Iwona Mozer-Lisewska Danuta Januszkiewicz-Lewandowska 《World Journal of Gastroenterology》 SCIE CAS 2017年第21期3815-3824,共10页
AIM To evaluate the association of IFNL3(IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C(CHC).METHODS The study enrolled 196 CHC Polish patients(82 women and 114 men in age 2... AIM To evaluate the association of IFNL3(IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C(CHC).METHODS The study enrolled 196 CHC Polish patients(82 women and 114 men in age 20-64) infected with hepatitis C virus(HCV) genotype 1. They were treatment na?ve and qualified to pegylated interferon alpha(PEG-IFN-α) and ribavirin(RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase(ALT), asparagine aminotransferase(AST) and total bilirubin(TBIL). The analysis of response to therapy included: sustained virological response(SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms(SNPs)(rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons. RESULTS Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC(grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217 C allele is associated with SVR(C vs A: P < 0.0001; dose of C allele: P = 0.0002) and nonrelapse(C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients(P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment(P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR(P = 0.016) and relapse(P = 0.024). CONCLUSION The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV. 展开更多
关键词 Hepatitis C virus Chronic hepatitis C Interferon lambda 3 interleukin 28B rs4803217
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Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C 被引量:1
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作者 Satoshi Yamagiwa Toru Ishikawa +7 位作者 Nobuo Waguri Soichi Sugitani Hiroto Wakabayashi Shogo Ohkoshi Takashi Tsukishiro Toru Takahashi Toshiaki Watanabe Shuji Terai 《World Journal of Hepatology》 CAS 2017年第5期252-262,共11页
AIMTo evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODSThe present study enrolled 1... AIMTo evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODSThe present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTSAmong the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV (> 60%) (OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677; 95%CI: 1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively. CONCLUSIONBoth TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients. 展开更多
关键词 TELAPREVIR Aged patients Hepatitis C virus genotype 1b interleukin 28B Simeprevir
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HCV感染者个体化基因检测与疗效评估
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作者 李艳华 王娟 +3 位作者 李宏伟 杨柳 郝晓柯 马越云 《免疫学杂志》 CAS CSCD 北大核心 2015年第10期888-892,共5页
目的检测丙型肝炎患者IL-28B基因型与HCV亚型,探索IL-28B基因变异与慢性丙型肝炎(CHC)型别和抗病毒疗效的相关性。方法收集诊疗的51例慢性丙型肝炎(CHC)患者资料,对48例CHC患者进行聚乙二醇干扰素联合利巴韦林(PEGIFN/RBV)治疗24... 目的检测丙型肝炎患者IL-28B基因型与HCV亚型,探索IL-28B基因变异与慢性丙型肝炎(CHC)型别和抗病毒疗效的相关性。方法收集诊疗的51例慢性丙型肝炎(CHC)患者资料,对48例CHC患者进行聚乙二醇干扰素联合利巴韦林(PEGIFN/RBV)治疗24~48周,评估抗病毒疗效。焦磷酸测序的高通量基因组测序系统检测分析IL-28B基因多态性和HCV的亚型。结果48例CHC样本的HCV基因分型检测结果显示,2个基因型感染率较高:1b(60.43%)、2a(27.08%);其获得SVR的比率分别是41.38%(12/29)和76.92%(10/13),(χ2=25.68,P〈0.05)。患者IL-28B rs8099917 TT型、12979860 CC型、12980275 AA型获得SVR的比例分别(25/27,92.41%)、(26/28,92.86%)、(24/27,88.89%)(P〈0.001)。同时,无论HCV 2a还是1b型感染者中,IL-28B野生型(12979860 CC型)均更易获得SVR,但2a型HCV比率更高。结论 IL-28B SNP与HCV基因型对于慢性丙型肝炎患者接受PEGIFN/RBV治疗方案预后具有很高的预测和评估价值。 展开更多
关键词 慢性丙型肝炎 白细胞介素28 单核苷酸多态性 HCV亚型 个体化
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Gene polymorphisms of interleukin-28, p21-activated protein kinases 4, and response to interferon-α based therapy in Chinese patients with chronic hepatitis B 被引量:7
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作者 YU Feng-xue ZHANG Xiao-lin +4 位作者 WANG Yan-ping MA Ning DU Hong MA Jian-min LIU Dian-wu 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第9期1726-1731,共6页
Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of ... Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of this study was to assess the relationship between the gene polymorphisms of interleukin-28 (IL-28), p21-activated protein kinase 4 (PAK4) and the response to interferon treatment in chronic hepatitis B patients. Methods Two hundred and forty interferon-naive treatment HBeAg seropositive chronic hepatitis B patients were enrolled in the present prospective nested case-control study. Peripheral blood samples were collected, including 92 with favorable response and 148 without response to the interferon treatment. Rs8099917, rs12980602, and rs9676717 SNP was genotyped using matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Results IL-28 genotype was not associated with response to interferon treatment (OR for GT/GG vs. TT, 0.881 (95% CI 0.388-2.002); P=0.762; OR for CT/CC vs. TT, 0.902 (95% CI 0.458-1.778); P=-0.766). Rs9676717 in PAK4 genotype was independently associated with the response (OR for CT/CC vs. TT, 0.524 (95% CI 0.310-0.888); P=0.016). When adjusting for age, gender, smoking, drinking, levels of hepatitis B virus DNA, and alanine aminotransferase (ALT), rs9676717 genotype TT appeared to be associated with a higher probability of response for interferon treatment (OR, 0.155 (95% CI 0.034-0.700); P=0.015). Conclusion Genotype TTfor rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success. 展开更多
关键词 chronic hepatitis B gene polymorphisms interleukin-28 interferon-a p21-activated protein kinase 4
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白细胞介素28B基因多态性在冷球蛋白阳性与阴性丙型肝炎患者中的比较 被引量:1
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作者 范晓红 吴赤红 +6 位作者 郑颖颖 王力芬 霍娜 邵翠萍 陆海英 徐小元 魏来 《中华肝脏病杂志》 CAS CSCD 北大核心 2013年第6期429-433,共5页
目的探讨冷球蛋白血症慢性丙型肝炎(CHC)患者白细胞介素(IL)28B基因多态性的分布。方法检测62例用聚乙二醇干扰素a-2a联合利巴韦林进行抗病毒治疗的CHC患者血清冷球蛋白性质,并检测IL-28Brs8099917、rsl2979860、rsl2980275的基因... 目的探讨冷球蛋白血症慢性丙型肝炎(CHC)患者白细胞介素(IL)28B基因多态性的分布。方法检测62例用聚乙二醇干扰素a-2a联合利巴韦林进行抗病毒治疗的CHC患者血清冷球蛋白性质,并检测IL-28Brs8099917、rsl2979860、rsl2980275的基因型。并分别检测患者血清HCVRNA在基线、治疗后4周与12周、治疗结束、治疗结束后24周时的水平。对计量资料用独立样本t检验或秩和检验进行两组间的比较,对计数资料用X2检验、Fisher’S精确概率法进行组间比较。结果27例患者血清冷球蛋白阳性,发生率为43.5%。IL-28Brs8099917TT基因型(63.0%与94.3%,x2=9.581,P〈0.01)与T等位基因(81.5%与97.1%,X2=8.554,P〈0.01)、IL-28Brsl2979860C等位基因(83.3%与94.3%,X2=3.896,P〈0.05)在冷球蛋白阳性CHC患者中的分布频率低于冷球蛋白阴性患者。结论IL-28B的基因型或等位基因分布在冷球蛋白阳性与阴性CHC患者间存在差异。 展开更多
关键词 肝炎 丙型 慢性 白细胞介素28 冷球蛋白血症
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白细胞介素28B基因的单核苷酸多态性与HCV感染的治疗及预后 被引量:1
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作者 陶剑 刘俊 贲昆龙 《中华肝脏病杂志》 CAS CSCD 北大核心 2011年第4期316-317,共2页
聚乙二醇干扰素α联合利巴韦林是目前治疗丙型肝炎普遍应用的方法.对于感染1型和4型基因型HCV的患者,40%治疗后获得持续病毒学应答(sustained virological response,SVR),而感染2型和3型基因型HCV的患者获得SVR率约为80%.非洲裔美国... 聚乙二醇干扰素α联合利巴韦林是目前治疗丙型肝炎普遍应用的方法.对于感染1型和4型基因型HCV的患者,40%治疗后获得持续病毒学应答(sustained virological response,SVR),而感染2型和3型基因型HCV的患者获得SVR率约为80%.非洲裔美国人(黑种人)1型基因型HCV感染者只有19%~28%在治疗后获得SVR,感染2型和3型基因型HCV的患者获得SVR率只有57%,比白种人和其他人种低. 展开更多
关键词 肝炎病毒 丙型 多态性 单核苷酸 白细胞介素28
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白细胞介素分子改造的研究进展 被引量:1
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作者 陆源 李利云 陈伟 《中国生物制品学杂志》 CAS CSCD 2015年第6期654-656,661,共4页
目的白细胞介素(interleukin,IL)是一类由多种细胞产生的具有重要免疫调节作用的细胞因子,在临床应用中发现,IL类药物的副作用大,半衰期短,清除率高,使其在临床的广泛应用受限。因此,对IL的分子结构进行改造,改善其理化性质和药代动力... 目的白细胞介素(interleukin,IL)是一类由多种细胞产生的具有重要免疫调节作用的细胞因子,在临床应用中发现,IL类药物的副作用大,半衰期短,清除率高,使其在临床的广泛应用受限。因此,对IL的分子结构进行改造,改善其理化性质和药代动力学性质,以获得生物学活性和稳定性更高而副作用更低的IL,是该类药物研发的重要发展方向。本文就近年对IL-2、IL-18、IL-28及IL-29分子改造的研究进展作一综述。 展开更多
关键词 白细胞介素-2 白细胞介素-18 白介素细胞-28 白介素细胞-29 分子改造
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类风湿性关节炎患者血清、关节液IL-35水平的变化及意义 被引量:8
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作者 王磊 董红 +1 位作者 孔继昌 杨继宏 《中国临床研究》 CAS 2017年第4期463-466,共4页
目的探讨类风湿性关节炎(rheumatoid arthritis,RA)患者血清、关节液白介素-35(interleukin-35,IL-35)水平变化及其与疾病的相关性。方法选取2013年3月至2015年12月间门诊及住院部诊治的RA发病初期患者74例、RA快速发展期患者98例以及... 目的探讨类风湿性关节炎(rheumatoid arthritis,RA)患者血清、关节液白介素-35(interleukin-35,IL-35)水平变化及其与疾病的相关性。方法选取2013年3月至2015年12月间门诊及住院部诊治的RA发病初期患者74例、RA快速发展期患者98例以及骨关节炎(Osteoarthritis,OA)患者58例为研究对象。采用酶联免疫吸附法(ELISA)测定研究对象的血清和关节液中IL-35水平,免疫比浊法测定血清C反应蛋白(CRP)水平。RA患者的疾病程度通过28个关节活动指数(28-Joint Count Disease Activity Score,DAS28)进行评估。结果与OA患者比较,RA发病初期与RA快速发展期患者实验开始时血清IL-35水平显著升高(P均<0.01),但应用抗风湿药物治疗12周后,两期患者IL-35水平均下降(P均<0.01)。与OA患者比较,RA快速发展期患者关节液IL-35水平明显升高,且高于三组患者各时点的血清IL-35水平,差异均有统计学意义(P均<0.01);治疗12周后降低,接近OA患者关节液IL-35水平。快速发展期RA患者中,关节液IL-35水平与CRP水平(r=0.327,P<0.05)及DAS28值(r=0.425,P<0.05)分别呈现中等相关。结论血清IL-35水平在RA发病初期和快速发展期均升高,且随治疗控制而下降;RA快速发展期关节液IL-35水平与炎症指标和疾病活动度指标相关;提示血清、关节液中的IL-35在RA疾病的进展和控制中发挥着重要作用。 展开更多
关键词 类风湿性关节 骨关节炎 白细胞介素-35 血清 关节液 28个关节活动指数
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