从中国乙型肝炎病毒耐药监测网络看当前耐药状况  

Establishment of the National HBV Drug Resistance Monitoring Network and the current status of HBV drug resistance in China

作　　者：曾艺军[1] 孙丽娜[1] 刘学恩[2] 张继明[3] 孙剑[4] 徐东平[5] 黄利华[6] 陆忠华[6] 张淑芹[7] 龙波 刘云华 陈士俊[10] 朱同海 刘锦堂[12] 汪茂荣[13] 王海舰 张跃新[15] 郝沛 韩悦[1] 于德敏[1] 张东华[1] 张欣欣[1] 庄辉[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,上海200025 [2]北京大学医学部,北京100191 [3]复旦大学医学院附属华山医院,上海200040 [4]广州南方医院,广东广州510515 [5]解放军第三〇二医院,北京100039 [6]无锡市传染病医院,江苏无锡214007 [7]吉林省肝胆病医院,吉林长春130062 [8]烟台市传染病医院,山东烟台264001 [9]昆明市第三人民医院,云南昆明650041 [10]济南市传染病医院,山东济南250000 [11]黑龙江省齐齐哈尔市第七医院,黑龙江齐齐哈尔161000 [12]山东省临沂市人民医院,山东临沂276000 [13]中国人民解放军第八十一医院,江苏南京210000 [14]徐州传染病医院,江苏徐州221000 [15]新疆医科大学第一附属医院,新疆乌鲁木齐830000 [16]上海市生物信息技术研究中心,上海200235

出　　处：《中国病毒病杂志》2013年第3期192-198,共7页Chinese Journal of Viral Diseases

基　　金：国家"十一五"艾滋病和病毒性肝炎等重大传染病防治科技重大专项(2009ZX10004-314);上海市2011年度"科技创新行动计划"研发基地与研发平台建设课题(11DZ2291900)

摘　　要：目的依托国家"十一五"重大传染病防治科技重大专项,对中国慢性乙型肝炎(乙肝)及乙肝后肝硬化患者核苷(酸)类药物治疗耐药情况进行监测和分析。方法采用网络信息与生物信息技术,建立并初步完善中国乙肝病毒(HBV)耐药网络监测平台,分析当前HBV逆转录酶(RT)区耐药相关基因突变的特点及耐药现状。结果建立了目前国内覆盖面最广的大型HBV基因多功能共享数据库。截至2012年12月,已对267家单位的9 998例乙肝患者进行了基因耐药检测,其中基因型明确的患者有7 551例,B基因型为2 421例,占32.06%(2 421/7 551),C基因型为5 088例,占67.38%(5 088/7 551),D基因型患者为42例,占0.56%(42/7 551)。在检测到原发性耐药相关位点突变及代偿性突变的5 207例(5 207/7 551,68.96%)患者中,C基因型占3 700例(3 700/5 088,72.72%),B基因型占1 482例(1 482/2 421,61.21%),C基因型的构成比明显高于B基因型(P<0.01);在原发性耐药位点突变中,主要耐药突变(rtM204V/I,rtA181T/V,rtN236T)的检出率为43.64%(3 295/7 551),其中M204I、rtA181T(sW172*)和rtA181V突变常见于C基因型(P值均<0.01),而N236T突变却在B基因型中多见(P<0.01)。在恩替卡韦继发性耐药突变的患者中,M204V比M204I更常见(P<0.01)。国内部分地区或医院抗病毒治疗的核苷(酸)药物应用方案纷繁复杂,不够规范,多药耐药的构成比高达1.73%(131/7 551)。结论为实现对乙肝患者耐药数据的实时监控、共享和标准化,本研究建立了我国HBV耐药监测网络平台。目前国内HBV基因突变及其导致的核苷(酸)类药物耐药现状值得关注,其致病相关机制有待进一步研究。Objective To establish the National Hepatitis B Virus （HBV） Drug Resistance Monitoring Net- work in accordance with the national ＂Eleventh Five Year Major Projects＂ for the research of infectious disea- ses and to study anti-HBV drug resistance among patients with chronic hepatitis B （CHB） in China. Methods With bioinformatics and network information techniques, the ＂National HBV Drug Resistance Monitoring Network＂ was established in China and the current characteristics of HBV resistant mutations was ana- lyzed. Results An extensive database of HBV drug resistance network was established in China. By the end of December 2012, a total of 9 998 CHB patients have been detected drug-resistant mutations and among which, 2 421 were categorized as HBV genotype B, 5 088 as genotype C, and 42 as genotype D. Of all HBV strains, 5 207 were found drug-resistant related mutations with 3 700 in genotype C and 1 482 in genotype B. The fre- quency of drug resistance mutations in patients infected by HBV genotype C （3 700/5 207, 72.72%） is high- er than that by genotype B （1 482/2 421, 61.21%） （P〈0.01）. Among all primary drug resistance muta- tions, the detection rate of major drug resistance is 43.64% and of which, M204I, A181T, A181V and rtA181T （sW172＊） mutations are common in patients infected with HBV genotype C （P〈0.05）, but N236T mutation is more frequent in patients with HBV genotype B （P〈0.01）. M204V shows higher frequen cy than M204I in ETV-resistant related mutations （P〈0.01）. The detection rate of multi-drug resistance is up to 1.73% （131/7 551）. Conclusions The National HBV Drug Resistance Network in China has been estab- lished for monitoring, sharing and standardizing the current HBV drug resistance status. The major HBV DNA mutations of antiviral resistance are associated with HBV genotypes.

关 键 词：乙型肝炎病毒 耐药 突变 耐药监测平台 

分 类 号：R512.62[医药卫生—内科学]