慢性肝病患者乙型肝炎病毒BCP变异对HBV DNA复制水平影响的研究

目的探讨乙型肝炎病毒慢性感染中C基因启动子(BCP)变异对HBV DNA复制水平的影响及其临床意义。方法采用PCR微板核酸杂交结合ELISA检测显示技术,检测74例乙型肝炎病毒慢性感染者BCP区核苷酸(nt)1762碱基A→T和1764碱基G→A联合突变。结果在74例乙型肝炎病毒慢性感染者中检出BCP区T1762 A1764突变24例(32.4％),BCP变异阳性组的HBV DNA含量(10~(8.2992±0.8665)拷贝/ml)显著高于BCP变异阴性组的含量(10~(7.1737±1.1539)拷贝/ml ) P<0.001)。结论 BCP变异可引起HBV致病力增强,复制水平提高。     

HBV S基因的反义锁核酸对乙型肝炎转基因小鼠HBV复制和表达的影响

目的: 探讨乙型肝炎病毒(hepatitis B virus,HBV)S基因的反义锁核酸(LNA)对乙型肝炎转基因小鼠HBV复制和表达的影响.方法: 将30只HBV转基因小鼠随机分为5组,每组6只. 第1组为5% GLU液对照组, 第2组为空脂质体对照组, 第3组为单LNA组, 第4组为S-ASODN脂质体组, 第5组LNA脂质体组. 反义LNA经尾静脉注入小鼠体内, 采用ELISA法检测血清HBsAg;PCR定量检测血清HBV DNA含量;免疫组织化学法检测肝细胞HBsAg的表达;自动生化分析仪检测ALB、ALT、BUN、CR、ApoA1、ApoB等指标;小鼠肝脏、肾脏做常规病理切片HE染色, 观察反义LNA对小鼠脏器的影响.结果: 注射反义LNA 1 d、3 d、7 d、14 d后,LNA-脂质体组对血清HBsAg的表达抑制率分别为41.7%、52.8%、57.8%及30.5%. 对HBV DNA的抑制率分别为18.5%、36.1%、52.9%和32.7%, 与对照组比较均有显著性差异(P <0.05);全自动生化分析仪检测血清中ALB、ALT、BUN、CR、ApoA1、ApoB等指标, 各组结果与对照组比较均无显著性差异(P >0.05);小鼠肝细胞HBsAg的表达显著低于对照组. HE染色显示小鼠肝肾功能及组织学未见异常.结论: HBV S基因反义LNA对乙型肝炎病毒转基因鼠HBV复制和表达有显著抑制作用.     

乙型肝炎孕妇HBV血清标志物与HBVDNA载量及ALT的相关性分析

目的 分析乙型肝炎(乙肝)孕妇HBV血清标志物、HBVDNA载量及ALT检测结果,为HBV感染孕妇的诊治提供参考。方法 回顾性分析2016年11月—2017年11月在我区孕检的120例乙肝孕妇的临床资料,应用酶联免疫吸附法检测血清五项HBV标志物,同时采用荧光实时定量PCR技术检测HBVDNA水平,酶速率法检测ALT,并对检测结果进行统计分析。结果 120例孕妇血清中,感染模式Ⅰ(大三阳)HBsAg(+)、HBeAg(+)、HBcAb(+)58例,占48.33%;HBVDNA(+)49例,占84.48%,其中HBVDNA>106IU/ml42例,占72.41%;ALT增高39例,异常率为67.24%。感染模式Ⅱ(小三阳)HBsAg(+)、HBeAb(+)、HBcAb(+)45例,占37.50%;HBVDNA(+)27例,占60.00%,其中HBVDNA>106IU/ml15例,占33.33%;ALT增高20例,异常率为44.44%。感染模式Ⅰ孕妇HBVDNA阳性率、HBVDNA>106IU/ml率和ALT异常率最高,感染模式Ⅱ孕妇次之。结论 HBV血清标志物与HBVDNA高载量和ALT水平密切相关,三者相结合能为孕妇的临床诊断、围产期干预措施以及疗效观察提供参考依据。     

Recognition of HBV antigens and HBV DNA by dendritic cells

BACKGROUND:Hepatitis B virus(HBV)is a hepatotropic, noncytopathic,DNA virus which can cause acute and chronic infection.Viral persistence is associated with a weak or absent specific immune responses to HBV,particularly the cellular immune response.Dendritic cells(DCs)are professional antigen-presenting cells with a unique T cell stimulatory aptitude that play a crucial role in the instruction of adaptive immune responses upon infection.An impaired function of DCs was suggested by recent studies to account for the T and B cell hyporesponsiveness in chronic HBV infection.This review summarizes recent insights into the recognition of HBV antigens by DCs. DATA SOURCES:Studies were identified by searching MEDLINE and/or PubMed for articles using the key words"hepatitis B virus (HBV)","dendritic cells","C-type lectins","mannose receptor", "toll-like receptor",and"dendritic cell-specific intercellular-adhesion-molecule-3 grabbing nonintegrin(DC-SIGN)"up to December 2009.Additional papers were identified by a manual search of the references from the key articles. RESULTS:DCs play an important role in the progress of hepatitis B,especially in the recognition of HBV.There are three main ways of recognition of HBV antigens by DCs. First,HBV DNA can be recognized by DCs through toll-like receptor 9(TLR9)which activates the NF-κB signal pathway and p38 MAPK to up-regulate the expression of interferon (IFN)regulatory factor 7(IRF-7)in a manner independent of type I IFN signaling,resulting in secretion of type I IFN and inflammatory cytokines,and induction of DC maturation and the adaptive immune response.Second,HBc/HBeAg cannot be recognized by DCs,but DNA or ssRNA encapsulated within HBcAg can be internalized by DCs through TLRs.Third,HBsAg can be internalized by DCs through the mannose receptor,which lacks the ability to induce DC maturation without the assistance of DC-SIGN.Meanwhile,there is some cross-talk among the three mechanisms,which induces an effective anti-viral response or HBV persistence. CONCLUSIONS:On the basis of these recognition processes, methods have been used to enhance the efficacy of DC-based vaccine against HBV and have been useful in the clinical application of HBV vaccine therapy.But the interactions between HBV antigens/HBV DNA and DCs are not clear, and cross-talk between TLRs and various ligands makes HBV antigen recognition by DCs more complicated.More efforts should be made to define the mechanisms and develop effective vaccines and therapies.     

Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection

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Distribution of HBV genotypes among HBV carriers in Benin： phylogenetic analysis and virological characteristics of HBV genotype E

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype. METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing. RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E. The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic diversity (nucleotide homology 96.7-99.2%). Based on the sequences in the basic core promoter (BCP) to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E. CONCLUSION: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics, is observed in HBV/E.     

HBV感染者胎盘组织HBV ccc DNA检测

目的建立HBV ccc DNA在胎盘组织中定性及定位检测方法,了解慢性HBV感染者胎盘组织中HBV ccc DNA的存在状况,进一步探讨其意义及乙型肝炎病毒母婴传播机制。方法选取首都医科大学北京地坛医院慢性乙型肝炎病毒感染者孕晚期胎盘组织40例,阳性对照肝组织标本3例,阴性对照为健康足月妊娠产妇胎盘标本,共5例。所有胎盘标本均分两份,分别于-80℃冷冻和福尔马林室温浸泡保存。冷冻标本采用质粒抽提法提取胎盘组织中HBV ccc DNA,液相PCR定性检测;福尔马林处理标本作石蜡切片,用于原位PCR定位检测。结果 40例标本中,液相PCR检测出HBV ccc DNA阳性者8例,其相应的血清HBV DNA均>105拷贝/ml。取该8例及另2例乙型肝炎患者孕晚期胎盘石蜡切片经HBV ccc DNA原位扩增,7例检测出HBV ccc DNA阳性,胎盘绒毛毛细血管内皮细胞、绒毛合体滋养层细胞、PBMC等多种细胞均存在HBV ccc DNA阳性信号。结论研究表明,胎盘组织HBV感染与孕妇血液中HBV DNA含量显著相关。胎盘组织的HBV ccc DNA原位PCR检测显示,HBV可感染胎盘各层细胞。羊膜上皮细胞中也发现HBV ccc DNA阳性信号。胎盘组织感染的HBV及其在这些细胞中的复制是否直接与HBV宫内感染相关尚需进一步研究。     

HBV plus HCV, HCV plus HIV, HBV plus HIV

Coinfection of hepatitis C virus (HCV), hepatitis B virus (HBV), and HIV is common due to shared modes of transmission. These coinfections accelerate the course of chronic liver disease and facilitate progression to cirrhosis and hepatocellular carcinoma. The viral interactions between these viruses are complex, and their treatment may be challenging for clinicians.     

慢性HBV携带者YMDD自然变异的追踪研究

目的 探讨慢性HBV携带者YMDD自然变异随时间的推移发生变化的情况.方法 随机选择未经抗病毒治疗的慢性HBV携带者103例,分别在开始、1年、2年时观察血清HBV DNA、HBV血清学标志物、肝功能、YMDD变异的变化情况.结果 在开始检测的103例慢性HBV携带者中,YMDD阳性27例,观察2年后4例转为非活动性H...     

HBV endemicity in Mexico is associated with HBV genotypes H and G

Hepatitis B virus(HBV)genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics,progression,severity of disease and antiviral response.Herein,we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico.HBV genotype H is predominant among the Mexican population,but not in Central America.Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence,apparently due to a rapid resolution of the infection,low viral loads and a high prevalence of occult B infection.During chronic infections,genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities,such as obesity,alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus.Hepatocellular carcinoma prevalence is low.Thus,antiviral therapy may differ significantly from the standard guidelines established worldwide.The high prevalence of HBV genotype G in the Americas,especially among the Mexican population,raises new questions regarding its geographic origin that will require further investigation.     

不同HBV标志物模式的乙型肝炎患者HBV表面大蛋白的检测及与HBVDNA水平的相关性

目的通过检测乙型肝炎病毒标志物（HBVM：HBsAg／抗-HBs、HBeAg／抗一HBe、抗一HBc）不同模式的乙型肝炎患者血清中乙型肝炎病毒外膜大蛋白（HBV—LP）、乙型肝炎病毒前s1抗原（HBVpreSl）、HBVDNA,探讨HBV—LP与HBVDNA及HBVM模式间的关系,研究HBV—LP用于乙型肝炎患者临床诊治的意义。方法采用酶联免疫吸附试验（ELISA）对HBV—LP、HBVpreS1和HBVM进行检测;采用荧光定量PCR方法对HBVDNA进行检测。结果乙型肝炎患者大蛋白检测结果与HBVDNA检测结果差异无统计学意义（X^2=1．97,P〉0．05）。HBV—LPA值随HBVDNA拷贝数的增加呈上升趋势,二者之间存在良好的相关性（r=0．565,P〈0．01）,在不同HBVDNA拷贝数组别间,HBV—LPA值差异有统计学意义（F=9．23,P〈0．01）。结论HBV—LP是反应HBV感染者体内病毒复制程度的良好的血清免疫学指标,血清中的HBV—LP与HBVDNA具有较好的相关性,特别是可作为HBeAg阴性患者体内监测病毒复制及预后判断的良好的血清学指标。     

168例慢性HBV感染者HBV基因型分布调查分析

目的 探讨HBV基因型与乙肝的临床转归关系.方法 应用PCR微板核酸分子杂交ELISA法检测168例慢性HBV感染者的HBV基因型,了解在各临床类型中HBV基因型的分布情况,阐明HBV基因型与HBeAg的关系;HBV基因型与乙肝临床转归的关系;HBV基因型与年龄性别的关系.结果 168例慢性HBV感染者中B基因型有78例占46.4396,C基因型有90例占53.57%.在肝硬化与肝癌病人中C基因型(73.17%)明显多于B基因型(26.83%),统计学分析有明显差异(P<0.05).90例C基因型病人HBeAg阳性62例,HBeAg阴性28例,两者比较有显著性差别(P<0.05).在高年龄组病人中以C基因型为主.结论 HBV基因型与乙肝临床转归有密切关系,C基因型是导致HBeAg持续阳性,引起肝硬化、肝癌的主要因素之一.     

肝癌患者血清中乙型肝炎病毒基因分型及临床意义

目的:探讨血清中乙型肝炎病毒(HBV)基因型及HBV DNA水平与肝细胞癌的关系。方法:应用巢式聚合酶链反应扩增乙型肝炎病毒与基因,用末端标记方法对PCR产物标记并直接测序,测序结果和GenBank中登录的标准基因型序列相比较,应用荧光定量PCR法检测HBV DNA水平。对61例肝癌、65例慢性乙型肝炎、10例乙型肝炎病毒携带者进行了检测。结果:136例中B基因型59例(43.4%)、C基因型77例(56.6%),随着病情加重,C基因型比例逐渐增高;不同基因型HBV感染的肝癌患者间HBV DNA水平差异有显著意义,P<0.05;在慢性乙型肝炎患者中,HBV DNA水平差异无显著性意义。结论:本地区乙型肝炎病毒以B、C基因型为主,乙型肝炎病毒C基因型及高水平的HBV DNA感染与肝癌的发生相关。     

乙型肝炎患者检测肝组织HBV-DNA的意义

为了探讨提高乙型肝炎病毒微量检出率的有效途径。采用PCR分别检测血清及肝穿刺组织HBVD-NA，血清检出总阳性率为41.7%，肝组织检出总阳性率为72.9%。在血清HBsAg阴性的病例中PCR血清检出阳性率为26.7%。肝组织检出阳性率为66.7%。早此可见PCR检测灵敏。准确、特别对血清HBVM难以检测的微量HBVDNA更有价值。两种标本来源相比肝组织较血清为优。