世居藏族患者乙肝病毒基因型及其临床特点分析

目的对世居藏族乙肝病毒(HBV)的基因型及其临床特点进行分析。方法对78例世居藏族患者的乙肝病毒基因分型、乙肝病毒DNA定量及其肝功能、两对半、肝纤维化指标、AFP、CEA、腹部B超等进行了检测,并对其临床特点进行分析。结果世居藏族乙肝患者乙肝病毒基因型主要以B型和C型为主,78例患者中B型41例,C型37例,B型和C型构成无统计学差异。C型患者HBVDNA定量、肝功能各指标、肝纤维化指标、AFP、HBe-Ag阳性率、CEA阳性率、肝硬化发生率、肝癌发生率、脾大发生率均显著高于B型患者(P<0.05～0.01)。结论世居藏族乙肝病毒基因型以B型及C型为主,C型患者肝硬化、肝癌发生率及肝纤维化和肝功能损害程度明显要高于B型患者,故在临床对C型世居藏族乙肝患者应加强针对性的防治。     

Genotype E: The neglected genotype of hepatitis B virus

Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.     

乙型肝炎病毒标志物临床意义的新认识

随着生物学技术的发展,人类对感染性疾病的认识也在不断深入.HBV DNA定量分析从最初的对HBV感染的诊断,到对疾病状况及长期预后的判断,近年来,又在抗病毒治疗疗效的评估、治疗方案的改变等方面具有关键的作用.血清中HBsAg的检测是40多年前发现HBV的关键,至今仍是诊断HBV感染的最基本标志物[1].目前认为HBsAg的清除最接近慢性乙型肝炎治愈,反映感染的免疫控制,如出现在肝硬化之前,则预后极佳[2].HBsAg定量技术的发展,使人们对乙型肝炎的自然史及抗病毒治疗应答都有了进一步的认识.这些“古老”的指标,焕发出新的生命.     

Subgenotype reclassification of genotype B hepatitis B virus

ABSTRACT: BACKGROUND: Nine subgenotypes from genotype B have been identified for hepatitis B virus (HBV). However, these subgenotypes were less conclusive as they were often designated based on a few representative strains. In addition, subgenotype B6 was designated twice for viruses of different origin. METHODS: All complete genome sequences of genotype B HBV were phylogenetically analyzed. Sequence divergences between different potential subgenotypes were also assessed. RESULTS: Both phylogenetic and sequence divergence analyses supported the designation of subgenotypes B1, B2, B4, and B6 (from Arctic). However, sequence divergences between previously designated B3, B5, B7, B8, B9 and another B6 (from China) were mostly less than 4%. In addition, subgenotype B3 did not form a monophyly. CONCLUSION: Current evidence failed to classify original B5, B7, B8, B9, and B6 (from China) as subgenotypes. Instead, they could be considered as a quasi-subgenotype B3 of Southeast Asian and Chinese origin. In addition, previously designated B6 (from Arctic) should be renamed as B5 for continuous numbering. This novel classification is well supported by both the phylogeny and sequence divergence of > 4%.     

Occult hepatitis B virus infection and its clinical implications

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Serum HBV level is usually less than 10⁴ copies/mL in these patients. Diagnosis of occult HBV infection requires sensitive HBV-DNA PCR assay. Several possibilities have been hypothesized as the mechanisms of occult HBV infection. These include: (i) mutations of HBV-DNA sequence; (ii) integration of HBV-DNA into host's chromosomes; (iii) infection of peripheral blood mononuclear cells by HBV; (iv) formation of HBV-containing immune complex; (v) altered host immune response; and (vi) interference of HBV by other viruses. The precise prevalence of occult HBV infection remains to be defined. The clinical implications of occult HBV infection involve different clinical aspects. First of all, occult HBV infection harbours potential risk of HBV transmission through blood transfusion, haemodialysis, and organ transplantation. Second, it may serve as the cause of cryptogenic liver disease, contribute to acute exacerbation of chronic hepatitis B, or even fulminant hepatitis. Third, it is associated with development of hepatocellular carcinoma. Fourth, it may affect disease progression and treatment response of chronic hepatitis C. Most of the previous studies utilized retrospective observation without control groups, and lacked direct association of occult HBV infection with specific pathological changes and disease progression. Highly sensitive, quantitative, and functional molecular analyses of HBV, combined with a well-designed prospective clinical assessment will provide the best approach for the future study of occult HBV infection.     

慢性乙型肝炎病毒基因型和亚型分布及与临床关系的探讨

目的了解乙型肝炎病毒(HBV)基因型和亚型分布情况,探讨其与临床的关系。方法采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对2006年1月至4月邯郸市传染病医院收集的108份HBV感染者的血清进行乙型肝炎病毒基因型和亚型分型,分析乙型肝炎病毒基因型与患者临床特点的相关性。结果108例慢性乙型肝炎患者感染的HBV主要以C基因型为主,占93.5%,B基因型占6.5%;B基因型中均为Ba型,C基因型中C2亚型为主,占C基因型的88.1%。不同性别感染基因型和C1、C2亚型分布差异无显著性意义。肝生化指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)比较提示C基因型患者的肝脏炎症较B基因型患者重,但差异无显著性意义。C基因型患者血清乙型肝炎病毒e抗原(HBeAg)阳性率显著高于B基因型患者。C基因型患者血清HBV-DNA略高于B基因型,但差异无显著性意义。C1、C2亚型间在肝功能、HBeAg阳性率和血清HBV-DNA载量方面差异均无显著性意义。结论慢性乙型肝炎患者感染的HBV主要以C基因型(C2亚型)为主。C基因型的患者血清HBeAg阳性率高于B基因型,C基因型患者与B基因型相比肝脏炎症程度、HBV-DNA载量差异无显著性意义。C1和C2亚型患者的临床特点相似。     

乙型肝炎病毒B基因型亚型的检测

目的:建立乙型肝炎病毒(hepatitis B virus,HBV)B基因型亚型的检测方法,并对其进行临床研究.方法:根据GenBank中20株Ba亚型,10株Bi亚型以及25株C型全长基因组序列设计Ba、Bj亚型特异探针以及巢式PCR引物.采用反向杂交技术将B亚型特异探针固定在芯片上,通过与地高辛标记的扩增产物杂交检测B型HBV亚型.对镇江地区200例B基因型HBV血清样本进行亚型分析并对患者HBVDNA YMDD变异进行检测.通过对部分血清中的HBV DNA进行序列分析验证该方法的准确性.结果:200例B基因型HBV患者中,Ba亚型184例(92%),Bj亚型16例(8%).在持续使用拉米呋啶的80例患者中,Bj亚型6(0%)例,均无YMDD变异,Ba亚型74例,YMDD变异21(28.4%)例.结论:镇江地区B基因型HBV以Ba亚型为主.Ba、Bj亚型在服用拉米呋啶1年后发生YMDD变异的几率并无统计学上的显著差异.     

徐州地区乙型肝炎病毒基因型分布及其意义

研究徐州地区乙型肝炎病毒的基因型分布及其与肝功能损伤、病毒复制水平的关系。采用PCR微板杂交-ELISA技术进行HBVDNA基因分型,并结合其HBVDNA定量值和丙氨酸转氨酶结果,分析乙肝病毒基因型的临床意义。徐州地区乙肝病毒基因型B、C和D型分别占26.7%、44.0%和17.3%,在急性乙型肝炎、慢性乙型肝炎和肝硬化中C基因型的HBVDNA定量值显著高于B型者(t=2.45,2.53和2.36,P=0.027,0.018和0.029)。D型和与D型相关的基因型发生重型肝炎的百分率为51.7%。C基因型是徐州地区的优势基因型,并与较重的肝损伤有关,而B型与较轻的肝损伤有关,D型可能与重型肝炎有关。     

Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

Hepatitis B virus(HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed nonresponders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.     

Recent advances in DNA vaccine of hepatitis virus

Nucleic acid vaccine or DNA vaccine is a hopeful vaccine to prevent and treat viral hepatitis. Problems exist in different DNA vaccines for HBV or HCV. Optimal animal model should be established study vaccine against hepatitis. Apart from the strategy to enhance the efficiency of DNA vaccine, combined use of cytokines or chemokines, different routes of inoculation, design of optimal vector, ISS insertion in the plasmid vectors, etc to enhance the efficiency of DNA vaccine are reviewed.     

Persistent occult hepatitis B virus infection： Experimental findings and clinical implications

Hepatitis B virus （HBV） is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection （SOI）. The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection （POI） where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.     

Recent advances in hepatitis C virus cell entry

More than 170 million patients worldwide are chronically infected with hepatitis C virus (HCV). Prevalence rates range from 0.5% in Northern European countries to 28% in some areas of Egypt. HCV is hepatotropic, and in many countries chronic hepatitis C is a leading cause of liver disease including fibrosis, cirrhosis and hepatocellular carcinoma. HCV persists in 50-85% of infected patients, and once chronic infection is established, spontaneous clearance is rare. HCV is a member of the Flaviviridae family, in which it forms its own genus. Many lines of evidence suggest that the HCV life cycle displays many differences to that of other Flaviviridae family members. Some of these differences may be due to the close interaction of HCV with its host's lipid and particular triglyceride metabolism in the liver, which may explain why the virus can be found in association with lipoproteins in serum of infected patients. This review focuses on the molecular events underlying the HCV cell entry process and the respective roles of cellular co-factors that have been implied in these events. These include, among others, the lipoprotein receptors low density lipoprotein receptor and scavenger receptor BI, the tight junction factors occludin and claudin-1 as well as the tetraspanin CD81. We discuss the roles of these cellular factors in HCV cell entry and how association of HCV with lipoproteins may modulate the cell entry process.     

Molecular analysis of hepatitis B virus isolates in Mexico： Predominant circulation of hepatitis B virus genotype H

INTRODUCTIONHepatitis B virus(HBV)is an important cause of morbidity and mortality worldwide.It is estimated that2billion people are infected with HBV and350million individuals suffer from chronic HBV infection in the world[1,2].Chronic HBV infection may …