基因芯片技术检测西藏拉萨地区的乙型肝炎病毒基因型

目的:研究西藏拉萨地区乙型肝炎病毒基因型的分布与特点.方法:采集92份西藏拉萨地区乙型肝炎患者的血清,参照GenBank中HBV DNA序列设计寡核苷酸探针并制备HBV基因分型芯片,利用套式PCR扩增HBV S基因部分片段,结合基因芯片、DNA测序和BioEdit软件进行基因分型检测,并对其与乙肝标志物、DNA含量、性别和民族之间的关系进行分析.结果:在92例血清标本中,套式PCR检测73例HBV DNA阳性可进行基因分型检测.其中B型13例(17.8%),C型18例(24.7%),D型39例(53.4%)和B/D混合基因型3例(4.1%).统计学分析3种基因型分布在不同乙肝标志物阳性、不同DNA含量和不同性别之间无差异,但与民族存在统计学差异(x~2=7.179,P<0.05).B型以汉族为主(9/13),而C、D型以藏族为主(12/18、28/39).将基因芯片分型的B、C、D型和B/D混合型进行DNA序列分析,表明两种分型方法的结果完全一致.结论:PCR结合基因芯片技术可用于HBV基因分型.西藏拉萨地区HBV基因型包括B、C、D和B/D混合型,其中以D型为主.     

仙居地区HBV基因型分布与若干相关问题的研究

目的:调查浙江仙居地区HBV基因型的分布,研究基因型与前C区变异的关系及基因型的临床稳定性.方法:全部病例样本均取自仙居地区出生的汉族人,HBV基因型及前C区变异均采用型特异性PCR法;部分病例分别于3、6、12、18月,重复采血复查基因型.结果:仙居地区HBV基因型分布:C型283例,B型51例,CB混合型19例;查nt(核苷酸)1 896变异51例,变异阳性者C型9/37例、B型7/10例、混合型3/4例;3、6、12、18月复查基因型,小部分病例发生改变.结论:仙居地区HBV基因型的分布,以C型为主占80.2%,其次为B型与CB混合型,分别占14.4%与5.4%;B型与CB混合型容易发生HBVnt 1896变异;基因型临床稳定性值得进一步研究.     

厦门市乙型肝炎患者病毒基因型的分析

目的:采用多对型特异性引物,通过巢式PCR法检测厦门市乙型肝炎患者血清中乙型肝炎病毒(HBV)基因型的分布情况.方法:收集250例HBV感染患者血清,提取血清中HBV DNA作为模板,设计HBV前S1基因和S基因中区域内设计出10条内外引物,并将其中8条型特异性内引物分成A,B两组,分别扩增A,B,C和D,E,F型HBV,然后将第2轮PCR产物以用30g/L琼脂糖进行电泳,根据PCR产物电泳显示的产物长度判定HBV基因型,以了解厦门HBV基因型分布情况.结果:共120例确定了HBV基因型.患者群中慢性乙型肝炎90例,占75.0%,急性乙型肝炎、肝炎肝硬化、原发性肝癌分别占5.8%(7/120)、6.7%(8/120)和12.5%(15/120).分型结果:B型58例(48.3%)、C型30例(25.0%),B/C混合型32例(26.7%).HBeAg阳性患者中B基因型占63.8%,B/C型混合感染21.9%;抗-HBe阳性患者中以B/C型混合感染68.8%,B型25.9%,HBeAg阳性组与抗-HBe组之间比较发现B型和B/C混合型之间(P<0.05).结论:厦门乙型肝炎患者HBV基因型以B型为主,B/C混合感染是一个值得重视的问题.     

肝细胞癌组织中HBV基因型的检测及分析

目的 了解肝细胞癌组织中HBV基因型分布状况及特点.方法 应用型特异性引物分型法和基因测序与生物信息学相结合的分型方法分析肝细胞癌组织中HBV基因型,并与HBV携带者血清中HBV基因型进行比较.结果 在63份肝细胞癌组织标本中,B、C、混合型B C和混合型B D基因型分别占20份(31.8%)、37份(58.7%)、4份(6.3%)和2份(3.2%).与HBV携带者血清相比,两者基因型构成比无显著性差异(P＞0.05).结论 中国南部地区的肝细胞癌组织中存在HBV基因型B、C、混合型B C和混合型B D,以C基因型为主,其次为B基因型.肝细胞癌组织中HBV基因型分布与当地HBV携带者基因型密切相关.     

原发性肝癌患者乙型肝炎病毒基因型与突变的地区性差异分析

目的 研究原发性肝癌患者乙型肝炎病毒(HBV)基因型、亚型和突变的地区性差异.方法 HBV阳性的原发性肝癌组织标本80例,其中广西地区20例,上海、浙江、江苏(长三角地区)60例.应用聚合酶链反应(PCR)扩增患者携带的HBV DNA序列,PCR产物直接纯化测序.用NCBI在线的软件viral genotyping tool确定HBV基因型,MEGA(Molecular Evolutionary Genetics Analysis,version 3.1)软件构建系统进化树和进行亚型分型及突变分析.结果 80例肝癌标本中,17例为B基因型(21.3%),57例为C基因型(71.3%),6例为B、C基因型混合感染(7.5%).对17例B基因型和57例C基因型的亚型分型,其中B基因型的亚型全部为B2型,C基因型的亚型有C1、C2、C5等三型,其中有12例为C1型(21.1%),44例为C2型(77.2%),1例为C5型(1.8%).广西地区的C1亚型35%(7/20)明显高于长三角地区的C1亚型8.5%(5/60),而广西地区的C2亚型20%(4120)明显低于长三角地区的C2亚型66.7%(40160).两地区HBV基因亚型分布在统计学上有显著差异.比较两地区的HBV序列还发现,广西地区B基因型CP区T1762/A1764呈现更高的突变性,有6例(100%)存在突变,而长三角地区只有2例(16.7%).结论 两地区原发性肝癌患者的HBV亚型分布和基因型B的CP区T1762/A1764突变率有显著差异.     

安康地区乙型肝炎病毒基因型分布及临床相关性研究

目的:探讨安康地区HBV基因型的分布状况及其与临床的相关性。方法:应用型特异性引物法检测陕西省安康地区1275例HBV感染者的HBV基因型,并分析了287例住院患者的基因型与临床的相关性。结果:1275例HBV感染者中B基因型902例(70.75%),C基因型370例(29.02%),B/C混合型3例(0.23%),未检测到其他基因型。287例住院患者基因型分布在性别上无明显差异(P=0.32),B型、C型患者在携带者、慢性肝炎、重型肝炎、肝硬化和肝癌中的分布无明显差异(P=0.45),在ALT水平及HBV DNA载量上无明显差异(分别为P=0.75,P=0.63);C基因型患者的HBeAg阳性率(70.37%)明显高于B基因型患者(44.17%),P0.001。结论:安康地区HBV感染者基因型以B型为主,C型次之,C基因型患者的HBeAg阳性率明显高于B基因型患者,B、C基因型在性别、疾病状态、肝脏炎症活动度及ALT水平上无显著性差异。     

乙型肝炎病毒基因的型特异引物结合型特异核苷酸分析

目的 研究HBV感染者HBV基因型分布状况,并建立一套适合HBV病毒株分型的简便可靠的分析方法.方法 通过对GenBank中全部S区基因序列(1000余条)进行比对,筛选A～H 8个基因型的型特异核苷酸.采用型特异引物PCR法分型,对238例慢性乙型肝炎患者所感染病毒中未能分型的病毒株再进行S区基因巢式PCR扩增、测序筛选出其特异性核苷酸从而判定其基因型.结果 238株HBV均得到分型.其中B型HBV感染者159例(男120例、女39例);C型69例(男52例、女17例);B+C混合型6例(男4例、女2例),B+D混合型4例(男3例、女1例).B型、C型、B+C和B+D昆合型检出率分别为66.8%、28.9%、2.5%和1.6%.未检出A、E、F、G、H基因型.结论 HBV感染以B、C基因型为主,B基因型高于C基因型.少数患者为B+C或B+D混合型感染.B、C基因型分布与性别无关(χ2=0.794,P＞0.05).     

乙型肝炎病毒基因型对干扰素α2b应答的影响

在HBV基因型特异引物下聚合酶链反应(PCR)扩增并检测1020例慢性乙型肝炎患者血清HBVDNA。其中136例接受干扰素α2b治疗,疗程6个月;观察患者乙型肝炎病毒血清标志物、HBVDNA、丙氨酸转氨酶(ALT)。1020例乙型肝炎患者中966例有基因分型结果;136例接受干扰素α2b治疗综合疗效(HBeAg阴转、HB-VDNA阴转、ALT复常)B型患者为40.9%(18/44),优于C型25.8%(16/62)及B/C混合型16.7%(5/30)(P>0.05)。乙型肝炎病毒不同基因型可以对干扰素α2b应答产生影响。     

乙型肝炎病毒基因型对乙型肝炎病毒变异的影响

目的探讨乙型肝炎病毒(HBV)基因型对病毒前核心区(前C区,nt1896)及基本核心启动子(BCP,nt1762/1764)变异的影响.方法416例血清HBsAg阳性、HBV DNA定量大于1.0×104拷贝/ml的患者,采用微流基因芯片检测HBV基因型、前C区及BCP变异.结果416例HBV感染者中406例有基因分型结果:B型20.9%、C型65.9%、BC混合型10.8%,10例患者未分出基因型.302例为HBeAg(-)且HBV DNA( )患者,其中248例(82.12%)有前C区或BCP变异,41.06%为前C区变异,31.12?P变异,2种同时变异为9.94%.B型患者前C区变异率为22.9%(20/87),与C型患者前C区变异率39.4%(108/274)及B、C混合型变异率40.0%相比均有显著差异(P＜0.01).在BCP变异及双变异,C型患者变异率均大于B型患者,但差异无统计学意义(P＞0.05).B、C混合型患者前C区及BCP变异率与C型相似.结论HBV基因型可影响病毒前C区及BCP变异,以C型为著.     

中国慢性HBV感染者基因型分布及其临床意义Meta分析

目的探讨中国乙型肝炎病毒(HBV)基因型分布及其临床意义。方法在万方数据库和NCBI数据库检索有关中国HBV基因型分布的研究论文,将中国分为不同HBV感染流行区,分析不同地区、民族和肝脏疾病类型人群HBV基因A、B、C、B/C、D型和其他基因型(非A~D基因型和非B/C混合型)分布。采用Meta分析基因型分布特点及其临床意义。结果在我国,HBV基因型主要以B基因型和C基因型为主,区域1(北部地区)HBV基因A、B、C、B/C、D型和其他型分别为0.1%、22.2%、69.1%、3.8%、0.5%和1.5%,其中C基因型比例显著高于其它区域(P0.05);区域2(中部地区)HBV基因A、B、C、B/C、D型和其他型分别为0.2%、62.6%、27.4%、3.8%、0.5%和2.4%,其中B基因型比例显著高于其它区域(P0.05);区域3(南部地区)HBV基因A、B、C、B/C、D型和其他型分别为0.6%、36.3%、49.4%、2.8%、2.6%和3.4%,其中C基因型比例显著高于区域2的27.4%(P0.05);区域4(青藏高原)感染HBV B基因型、C基因型、D基因型和其他基因型分别为6.0%、22.5%、11.7%和59.3%,其中C/D混合型比例显著高于其他区域(P0.05);藏族人群C/D混合型比例(49.3%)显著高于其他民族(P0.05),哈萨克族D基因型比例(58.1%)显著高于其他民族(P0.05);C基因型与慢性乙型肝炎、HBV相关性肝硬化和肝癌显著相关(OR=1.979、OR=3.888、OR=4.399,P0.001)。结论不同地区和民族HBV基因型分布显著不同,B基因型可能是中国HBV起源基因,而感染C基因型更有可能引起严重的肝脏疾病。     

Hepatitis B Antigen and Prevention of Post-Transfusion Hepatitis B

Abstract. Screening for hepatitis B antigen (HB_sAg) in the serum of blood donors and exclusion of antigen-positive blood units have reduced the frequency of post-transfusion hepatitis but several cases of hepatitis B still occur in association with transfusions. One explanation for this is probably that HB_sAg is not an indicator of infectivity. Thus healthy carriers of the antigen seem to have low infectivity while carriers with chronic liver disease as well as donors incubating hepatitis B probably present a great risk.     

Hepatitis B

The hepatitis B virus is a hepatotropic virus that can produce a variety of clinical syndromes in patients ranging in age from infants to elderly adults. Worldwide, it is among the leading causes of fulminant hepatic failure, cirrhosis, and hepatocellular carcinoma. Recent advances have led to effective antiviral treatments using interferon and nucleoside analogues. Highly effective vaccinations also are used widely and ultimately may lead to eradication of this life-threatening virus.     

Hepatitis B

Opinion statement  

Hepatitis B

During a 2 1/2-year period, 200 cases of hepatitis B with positive antigen (HB Ag+) were studied. The patients were divided into four major groups according to suspected mode of transmission: blood or blood products (12.0%), needles (36.5%), personal contact (20.5%), and unknown (31%). Many in the group classified as personal contact were couples, and persistent antigenemia in one partner was frequent. Of the 200, 61.5% were male. The incidence of HB reached its peak in the last half of 1971 and has decreased in the first half of 1972. Arthralgias and/or rash occurred in 32.5% of the entire group and were most common in white females. Twelve males and one female had multiple symptomatic episodes of jaundice. Death occurred in 15 patients; 5 deaths were disease related, 3 were from acute hepatic necrosis, 1 from post-necrotic cirrhosis, and 1 from hepatoma.This study was supported in part by Grant No. HL 02254 from the National Institutes of Health, US Public Health Service.     

Hepatitis B vaccination

Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response >36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P <0.05, group I vs III). In those who did not respond, a significant (P < 0.02) lower helper/inducer (T ₄)class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed.This research was funded by the Veterans Administration, Cincinnati, Ohio; and Merck, Sharp and Dohme Laboratories.     

Hepatitis B virus

Recent developments in molecular biology have advanced our understanding of the pathogenesis of HBV-induced disease. New data derived from the molecular analysis of clinical material have begun to bridge the gap between bench research and the clinical arena. In this review, we consider topics that have relevance to clinical management and that have not been summarized in the recent literature. The recent advances that have been made in the areas of HBV variants,in vitro cell culture systems, and extrahepatic infection are discussed in greater detail.Supported by grants from the American College of Gastroenterology (B.Y.), Gulf Coast Regional Blood Center (C.N., B.Y.), and Schering Corporation (B.Y.).     

乙型肝炎疫苗免疫

根据2000年世界卫生组织、联合国儿童基金会/艾滋病基金会和美国疾病控制中心报告,死亡率列世界前10位的传染病顺序为:(1)下呼吸道感染;(2)艾滋病;(3)腹泻病;(4)结核病;(5)疟疾;(6)麻疹;(7)乙型肝炎(简称乙肝);(8)百日咳;(9)新生儿破伤风;(10)肠道寄生虫病。全世界约20亿人有现症或既往乙肝病毒     

Hepatitis B vaccines

Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic dis-ease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.