乙型肝炎病毒S区基因变异研究进展

乙型肝炎病毒（HBV）为一嗜肝细胞DNA病毒,不仅可以引起隐匿性、急性和慢性病毒性肝炎,还与肝硬化和肝细胞癌的发生发展密切相关。虽然通过对HBV和宿主及其相互作用的研究,已经发展了有效的预防疫苗和多种抗病毒药物,但HBV感染仍是世界范围内的公共健康问题[1-2]。本文针对HBV S基因的结构和功能上,以及目前关注较多的免疫逃逸、隐匿性肝炎和耐药突变引起方面S基因变异的研究进展作一综述。     

乙型肝炎病毒基因分型与肝细胞癌发生发展的研究进展

乙型肝炎病毒(hepatitis B virus,HBV)基因分型与抗病毒治疗的反应及肝脏疾病的进展密切相关.本文就HBV的基因分型、地理分布、传播方式及其与肝细胞癌的发生发展作一综述.综合各项研究发现,HBV基因分型与肝细胞癌的临床病理特征有着广泛的联系,其中感染基因型B的患者与大肝癌、多发肿瘤及血管侵犯密切相关.在治疗上,感染HBV基因型A和B的患者对于干扰素的治疗反应较好,但是对于核苷酸类似物,不同的基因型对其反应差异不大.因此,HBV基因分型可以作为病毒基因标志来预测肝细胞癌的发生发展,同时可以帮助医生在临床工作中选择最佳的治疗方案,指导肝癌的预防.     

乙型肝炎病毒HBx蛋白与原发性肝癌的关系研究进展

乙型肝炎病毒(HBV)感染是一个世界性的健康问题.据估计,全世界目前大约有三亿五千万人感染HBV,而HBV感染与肝细胞性肝癌(HCC)的发生密切相关,尤其在HBV感染高度流行的区域如东南亚和南撒哈拉的非洲地区,HBV感染是HCC的主要病因[1].     

慢性乙型肝炎抗病毒治疗的进展

由于乙肝病毒(HBV)是肝炎发生和发展的基础．因此清除病毒是慢性乙型肝炎治疗的关键。消除病毒的策略有2种：清除感染了HBV的肝细胞和抑制(或杀灭)病毒本身。     

病毒性肝炎最新进展HBV／HCV相关肝细胞癌中，HBV前C基因/C基因的基因型、突变类型及病毒学分析

作研究了肝细胞癌（HCC）患HBV和HCV的复制情况，以及前C基因／C基因的突变类型。研究涉及到38例HCC患，其中18例为HBV／HCV混合感染，20例为HBV单纯感染。还有23例HBV/HCV混合感染但无肝细胞癌的患被定为对照组。通过对HBV和HCV基因组的定性和定量测定来评价病毒复制的活跃性。HBV前C基因／C基因以及与病毒复制相关的前基因组外亮信号用直接测序法来测定。     

慢性HBV感染免疫治疗新进展

慢性HBV感染有发展为肝硬化和肝细胞癌高风险.IFN-α、拉米夫定、阿德福韦、恩替卡韦是目前批准用于HBV感染的治疗药物.这些药物是防止慢性HBV感染者发展为肝硬化和肝细胞癌的唯一策略.然而,以发生HBeAg血清转换、血清丙氨酸转氨酶正常和血清HBVDNA水平转阴作为评价疗效标准,这些药物的治疗效率仅占接受治疗者的20%-30%.应用拉米夫定或阿德福韦长期治疗可能导致药物耐药,从而导致延长了应用其他核苷类似物治疗的期限.目前抗病毒治疗的缺陷使我们有必要寻找更好的治疗策略.而提高慢性HBV感染者病毒特异性T细胞活性的特异性和非特异性免疫治疗策略为抗HBV感染提供了新的治疗方向.这些免疫治疗策略包括,过继性HBV免疫、PEG干扰素和治疗性疫苗等.     

乙型肝炎病毒全S蛋白结合蛋白基因的筛选

HBV与肝硬化、肝细胞癌的发生发展密切相关[1],通过其表达的病毒蛋白与肝细胞蛋白相互作用导致疾病进展.本研究中,我们对全S基因编码产物功能进行了探讨,并以其为靶蛋白,利用酵母双杂交技术寻找其与肝细胞相互作用的蛋白质,以进一步探讨HBV致病机制.     

羧基末端截短型乙型肝炎病毒表面抗原中蛋白反式激活作用的研究

0 引言乙型肝炎病毒(HBV)的感染,不仅引起急、慢性病毒性肝炎,而且与肝纤维化、肝细胞癌的发生、发展过程密切相关。病毒进入到肝细胞之后,肝炎病毒蛋白在肝细胞内不是孤立存在的,病毒基因组在肝细胞     

乙肝病毒的基因分型对患者治疗有临床意义吗？

世界上有20亿人曾感染过乙肝病毒（HBV）且3．5亿人成为慢性携带者。从无症状携带状态到致死的严重肝病，HBV感染的临床过程变化各异：暴发性肝炎及与肝硬化和肝细胞癌相关的慢性肝炎。基本上，病毒和宿主的特性可解释病毒感染的临床结果。关于HBV，有研究已发现该病毒的血清学异质性，这导致近期HBV基因型的划分，可能也影响了临床病程。     

乙型和丙型肝炎病毒蛋白反式激活作用机制及其意义的研究进展

编者按乙型肝炎病毒(HBV)和丙肝炎病毒(HCV)感染不仅引起急性、慢性病毒性肝炎,而且与肝纤维化(LF)、肝细胞癌(HCC)的发生、发展密切相关.     

The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B

Background  Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver. Purpose  To review the studies published to date regarding the association of HBV genotypes and subgenotypes in the development of adverse sequelae from HBV. Methods  Review of the literature for articles describing studies of HBV genotype/subgenotypes and development of HCC, cirrhosis, and liver-related death. Results  Eight genotypes of HBV (A through H), which differ from each other in viral genome sequence by more than 8%, and multiple subgenotypes, which differ from each other by 4–8% have been identified. Recently, studies investigating the association between the risks of developing HCC and cirrhosis by specific HBV genotypes and subgenotypes have reported marked differences in outcome. Certain HBV genotypes and subgenotypes, including genotype C, B2-5, and F1, appear to be associated with a higher risk of developing HCC, and others, including genotypes B1, B6, and A2, appear to be associated with a lower risk of complications of HBV. Our understanding of the role of HBV genotypes and subgenotypes on the outcome of HBV infection is limited, as few population-based prospective studies have been performed and most studies compare only the outcome in areas where two genotypes predominate whereas others have not examined subgenotypes. Conclusions  Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.     

Geographical and genetic diversity of the human hepatitis B virus

Hepatitis B virus (HBV) is one of the most widely distributed viruses that infect humankind. Distinct clinical and virological characteristics of the HBV-infection have been reported in different geographical parts of the world and are increasingly associated with genetic diversity of the infecting virus. HBV is classified into genotypes and subgenotypes that are associated with ethnicity and geography. The genetic diversity of HBV in its various aspects has been the subject of extensive investigations during the last few decades. Since molecular epidemiology research tools have become widely available, the number of new publications in this field has grown exponentially. This review summarises the recent publications on the geographical distribution of genetic variants of HBV, and proposes updated criteria for the identification of new genotypes and subgenotypes of the virus.     

Hepatitis B virus: origin and evolution

Summary. The pathogenesis of hepatitis B virus (HBV) is complex and it appears that molecular variants play a role in this process. HBV undergoes numerous rounds of error prone production within an infected host. The resulting quasispecies are heterogeneous and in the absence of archaeological records of past infection, the evolution of HBV can only be inferred indirectly from its epidemiology and by genetic analysis. This review gathered the controversies about the HBV origin and factors influencing its quasispecies. Also, it provided some evidence on how HBV genotypes correlated with human history and patterns of migration. It is our belief that this topic deserves further attention and thus it is likely that more critical research work will be performed to elucidate the unknown mechanisms and processes in this area.     

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses).The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field,updates several recent reviews on HBV genotypes and subgenotypes.     

HBV/HDV co‐infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co‐infection in this region. We studied 92 patients HBsAg⁺/anti‐HDV IgG⁺ followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV‐3) was found in all of the HBV/HDV‐infected patients that could be genotyped for HDV, confirming that HDV‐3 can associate with non‐F HBV genotypes. However, a HDV‐3 mutant was found in 29.3% of patients and was more frequently associated with non‐F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV‐3 with non‐F HBV genotypes.     

乙型肝炎病毒基因型

乙型肝炎病毒(hepatitis B virus,HBV)是嗜肝DNA病毒家族的重要成员,所引起的慢性乙型病毒性肝炎及肝衰竭、肝硬化、肝癌等是严重危害人民健康的疾病.据统计,目前我国有慢性乙型肝炎患者2000万人,是我国现阶段最为突出的公共卫生问题之一.HBV遗传变异率很高,有8个基因型,由于独特的流行病学特性,多数又可以分为不同的基因亚型.另外DNA基因型的高度异质性使重组基因型也增加了.有研究证实HBV基因型与疾病进展关系密切.不同基因型HBV的流行病学特征不同,同时其临床感染特点和致病性也有差异.本文综述了本领域研究进展,包括HBV生物学特性、基因型与基因亚型、重组基因型、HBV基因型的流行病学特点以及HBV基因型与临床等方面.     

HBV epidemiology and genetic diversity in an area of high prevalence of hepatitis B in southern Brazil

Background

Hepatitis B virus (HBV) infection is a major public health problem in Brazil. HBV endemicity is usually moderate to low according to geographic regions, and high prevalence of this virus has been reported in people of some specific Brazilian counties, including those with a strong influence of Italian colonization in southern Brazil. Analysis of HBV diversity and identification of the main risk factors to HBV infection are necessary to understand hepatitis B epidemiology in these high prevalence regions in southern Brazil.

新疆维吾尔族慢性乙型肝炎病毒感染者病毒基因型及亚型分布特点

目的 了解新疆维吾尔自治区(简称新疆)维吾尔族慢性HBV感染者基因型、基因亚型分布情况及其与预后的关系.方法 采用聚合酶链反应限制性片段长度多态性分析方法,分析109例新疆维吾尔族慢性HBV感染者感染病毒的基因型及基因亚型.多标本均数比较采用单向方差分析.结果 109例新疆维吾尔族慢性HBV感染者,其中慢性乙型肝炎88例,乙型肝炎肝硬化17例,肝癌4例.13基因型HBV感染者9例,占8.3%,C基因型感染者50例,占45.9%,C/D基因型重组体32例,占29.4%,D基因型感染者18例,占16.5%,C基因型、C/D基因型重组体为主要基因型.经过聚合酶链反应限制性片段长度多态性分析及测序检测,鉴定9份B基因型HBV,均为Ba亚型.50例C基因型HBV感染者病毒基因亚型分布情况:Cl亚型27例,占54%,C2亚型23例,Cl亚型比C2亚型感染者多.在慢性乙型肝炎、乙型肝炎肝硬化、肝癌患者中,HBV Ba基因亚型感染者分别为8例(9.1%)、1例(5.8%)和0例;C2基因亚型感染者分别为17例(19.3%)、8例(47.5%)和2例(50%);C/D基因型感染者分别为29例(33.0%)、2例(11.9%)和1例(25%),随着病情加重,Ba基因亚型和C/D基因型感染者所占比例呈下降趋势,C2基因亚型感染者所占比例增加.结论 新疆地区维吾尔族慢性HBV感染者以Cl基因亚型为主,新疆维吾尔族慢性HBV感染者存在C/D基因型重组体.C2基因亚型HBV感染预示病情严重,预后差.