慢性乙型肝炎病毒感染相关基因多态性的研究进展

乙型肝炎病毒(HBV)感染是人类最常见的感染之一,感染后表现为自身清除病毒或持续感染,结局差异较大.研究表明除了病毒本身影响外,基因多态性决定的个体遗传因素可能成为HBV感染不同结局的主要原因.     

人类白细胞抗原与乙型肝炎病毒感染转归的研究进展北大核心CSCD

人感染HBV可表现为隐性、急性或急性重型HBV感染,之后有的清除病毒表现为自限性HBV感染,而约90％的儿童和10％的成人则转为HBV携带者或慢性乙型肝炎,其中慢性乙型肝炎可进一步发展成肝硬化和肝细胞癌。目前认为,HBV感染转归主要取决于宿主的免疫反应。人类白细胞抗原（human leukocyte antigen, HLA）作为免疫系统的关键组成部分,在HBV感染免疫反应中扮演重要角色。     

激活肝内天然免疫治愈乙型肝炎的进展和新策略

宿主天然免疫和适应性免疫应答对HBV的清除至关重要。慢性HBV感染者体内针对HBV的天然免疫和特异性免疫应答存在缺陷,不能有效清除病毒,导致病毒持续复制和肝脏炎症。除了直接抑制HBV,针对宿主免疫的治疗策略如刺激或重塑抗病毒免疫也是实现慢性乙型肝炎患者功能性治愈的重要手段之一。肝脏是HBV感染的靶器官,因此研究HBV感染对肝内免疫微环境的影响是当前调控肝内抗病毒免疫应答的新药研发热点。主要阐述了HBV感染相关天然免疫应答的研究进展和激活肝内天然免疫应答治愈乙型肝炎的新策略。     

慢性乙型肝炎免疫功能缺陷与抗病毒治疗现状

乙型肝炎病毒(HBV)感染人体后,特异性细胞免疫是发病的关键环节,细胞免疫应答低下是HBV持续感染的关键因素.目前抗病毒治疗存在持续应答率低、疗程长、病毒变异等一系列问题,主要原因是抗病毒药物只能抑制HBV复制,都不能彻底清除共价闭合环状DNA(cccDNA),也与患者免疫缺陷不能得到充分恢复有一定的关系.因此,抗病毒治疗过程中,如何发挥现有药物各自优点,同时提高患者的特异性细胞免疫功能,加强免疫介导的病毒清除,从而达到彻底清除HBVcccDNA 的目的 ,应成为关注的重点.     

中老年乙型肝炎病毒感染患者HBV前S1抗原、ALT与HBV-DNA病毒载量的关系

乙型肝炎病毒(HBV)感染是肝硬化、肝癌发生的重要危险因素,我国HBV病毒携带者达1.2亿[1],血清学标志物两对半是HBV病毒感染的常规检测方法,前S1抗原(PreS1)、HBV-DNA定量也是近年推广较快的反映HBV病毒复制情况的标志物,本文旨在研究HBV感染患者血清PreS1、谷丙转氨酶(ALT)及HBV-DNA之间关系.     

HBV感染慢性化的免疫耐受机制

HBV感染机体后,机体抗病毒免疫强度的高低,能否及时、有效、彻底清除病毒可能成为决定急性自限性感染或慢性感染的标志。HBV作为抗原,欲长期持续存在于宿主体内,必须逃避宿主免疫系统的监视与攻击,即造成免疫耐受环境,免疫耐受是HBV感染慢性化最主要的机制。免疫耐受与机体免疫系统发育成熟程度有关。成人、儿童、幼儿感染HBV后分别有5％、30％、95％的患者成为慢性HBV感染者。表明免疫成熟程度是决定HBV持续感染的重要因素。     

HBV诱导的髓源性抑制细胞亚群及其在慢性HBV感染中的作用

HBV是一种嗜肝性DNA病毒,HBV感染不会引起直接的肝细胞病变,宿主免疫应答决定了病毒能否被清除,同时也是导致HBV相关肝脏疾病的主要原因。髓源性抑制细胞(MDSC)是一群起源于骨髓的非淋巴免疫抑制性细胞,多种病理条件下调节固有和获得性免疫应答。研究发现慢性乙型肝炎患者外周血中MDSC明显高于健康人群,主要介绍了HBV诱导的MDSC亚群在HBV持续感染和肝脏病理学机制中的作用。     

慢性乙型肝炎病毒感染患者血清 preS1 Ag水平变化及意义

目的：探讨慢性乙型肝炎病毒（ HBV）感染患者血清表面抗原蛋白前S1抗原（ preS1Ag）水平变化及意义。方法选择确诊HBsAg阳性患者2545例（ HBV感染组）、HBsAg阴性即健康体检者172例（对照组）,均同步检测外周静脉血HBsAg、HBeAg、preS1Ag及HBV DNA。结果 HBV感染组中preS1Ag阳性1845例（72．50％）, HBeAg阳性808例（31．75％）,HBV DNA阳性1173例（46．09％）;对照组preS1Ag阳性4例（2．33％）;两组间preS1Ag阳性率比较差异有统计学意义（P＜0．05）。 HBV感染组preS1Ag阳性患者中HBsAg＞250 ng／mL、HbeAg阳性、HBV DNA≥103 copy／mL的比例均大于preS1Ag阴性患者（P均＜0．05）。 HBV感染组HBV DNA≥103 copy／mL的患者中,preS1Ag阳性组与preS1Ag阴性组间不同HBV DNA病毒载量差异无统计学意义（ P均＞0．05）。结论 preS1Ag能较好地反映HBV的感染状态及病毒复制情况。     

促进细胞免疫学应答——慢性乙型肝炎中医药治疗的机制

<正>慢性乙型肝炎(Chronic hepatitis B,CHB)是世界范围的重大传染病,其发生发展受病毒因素(如病毒基因型、病毒变异、病毒复制等)与机体因素(如生物遗传特征、免疫状态、细胞凋亡、细胞坏死等)[1]两方面因素及其相互作用的影响。持续乙型肝炎病毒(Hepatitis B Virus,HBV)复制和宿主抗HBV免疫功能低下是CHB两个重要的临床特征。HBV感染后形成对HBV特异性免疫耐受,导致病毒持续复制不能被清除是HBV感染慢性化、疾病迁延不愈的     

乙型肝炎病毒变异与重症肝炎关系探讨

乙型肝炎病毒(HBV)是一种高度变异的病毒,由于病毒变异后往往引起抗原性和致病性改变,所以认为HBV感染在临床上出现的不同疾病谱与病毒变异有关。乙型病毒性肝炎病情轻重由宿主和病毒两方面决定,随着HBV变异研究的不断深入,变异所引起的生物学意义也不断被人们所认识,它既可使肝病加重,又可使病毒逃避机体免疫而持续感染[1 ] 。本文就重型肝炎(重肝)相关的HBV变异,并对HBV变异引起重肝的机制作如下综述。一、前C区终止密码子突变HBV前C区1896G→A突变,产生一终止密码子TAG ,使HBeAg不能转录合成。在日本、以色列和南欧一些地区…     

Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion

In high endemic areas of hepatitis B virus (HBV) infection, the vast majority of infection is acquired perinatally or during early childhood. The age of the patient is, therefore, almost equivalent to the duration of HBV infection. The natural history of chronic HBV infection consists of three chronological phases: immune tolerance, immune clearance and low replicative phases. The prevalence of hepatitis B e antigen (HBeAg) in asymptomatic HBV carriers is around 90% before 15 years of age, and decreases remarkably to less than 10% after 40 years of age. The immune clearance phase is characterized by a series of hepatitis flares and remissions. These will be followed eventually by HBeAg seroconversion, which is usually accompanied by remission of liver disease and confers favourable outcome. However, patients with persistent HBeAg seropositivity over 40 years of age are associated with a significantly higher risk for progression to cirrhosis than those with HBeAg seroconversion before 40 years of age, and thus should be considered as patients with 'delayed' HBeAg seroconversion. Antiviral or immunomodulatory therapy should be considered seriously for these patients.     

Favorable outcome of liver transplantation despite a high hepatitis B virus replication: beyond the limits?

Patients with end-stage liver disease due to chronic hepatitis B virus (HBV) infection with a persistent viral replication are generally denied liver transplantation (LT). We report the case of a patient who presented with the emergence of a YMDD escape mutant virus under lamivudine treatment, and developed terminal liver failure requiring LT. Pre-LT introduction of adefovir led to only a mild decrease in replication. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) that was started perioperatively, and also continued lamivudine and adefovir after LT. One year after LT, there was no evidence of HBV infection recurrence. This observation suggests that persistent high HBV replication might not be a contra-indication to LT, providing adequate and effective prophylaxis is given, using HBIG and antiviral drug combination therapy.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.     

Occult Hepatitis B Infection and its Possible Impact on Chronic Hepatitis C Virus Infection

As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV) replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV) related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.     

慢性肝病患者HCV与HBV重叠感染与预后

目的探讨ＨＣＶ与ＨＢＶ重叠感染对慢性肝病过程、预后及对乙型肝炎病毒复制的影响。方法应用第二代抗＿ＨＣＶＥＬＩＳＡ及ＲＴ＿ＰＣＲ法测定１８７例ＨＢｓＡｇ阳性慢性肝病患者抗＿ＨＣＶ及ＨＣＶ＿ＲＮＡ，并对ＨＣＶ与ＨＢＶ重叠感染者的肝损害，ＨＣＶ，ＨＢＶ间的相互作用及预后进行分析。结果抗＿ＨＣＶ，ＨＣＶ＿ＲＮＡ的阳性率在慢性肝炎（轻度）１３．３％，慢性肝炎（中～重度）１６．１％，肝硬变２２．７％，慢性重型肝炎６３．６％，肝细胞癌１３．３％。平均阳性率１８．２％，慢性重型肝炎抗＿ＨＣＶ，ＨＣＶ＿ＲＮＡ的检出率最高，明显高于肝脏损害的其他肝病（Ｐ＜０．０５），近半数以上ＨＣＶ慢性感染已与ＨＢＶ重叠感染。结论ＨＣＶ与ＨＢＶ重叠感染的慢性肝病患者预后较差。但并未发现ＨＣＶ对ＨＢＶ复制具有阻遏作用。     

Hepatitis B virus infection:defective surface antigen expression and pathogenesis

Hepatitis B virus(HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.     

Association of single nucleotide polymorphisms in microRNAs with susceptibility to hepatitis B virus infection and HBV‐related liver complications: A study in a Saudi Arabian population

The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV‐cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR‐based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV‐induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.     

40岁以上HBeAg阳性和阴性慢性乙型肝炎病毒感染者的临床特点比较

目的探讨40岁以上HBeAg阳性和HBeAg阴性慢性HBV感染者的临床特点。方法收集40岁以上慢性HBV感染者共186例,其中HBeAg阳性组93例,HBeAg阴性组93例。结果 40岁以上HBeAg阳性慢性HBV感染者男性为多(76.34%),并且多有乙型肝炎家族聚集现象(78.49%);40岁以上HBeAg阳性慢性HBV感染者的HBV DNA水平与ALT水平均高于HBeAg阴性慢性HBV感染者;40岁以上乙型肝炎肝硬化患者中,HBeAg阳性者占少数;40岁以上乙型肝炎肝硬化失代偿期患者中,HBeAg阳性者多合并腹水形成,而HBeAg阴性者既可见腹水形成,又可见上消化道出血。结论 40岁以上HBeAg阳性慢性HBV感染者多见于男性,多具有家族聚集现象,HBeAg阳性肝硬化患者所占比率较低,但HBV DNA水平较高,肝脏的炎症活动明显,病情进展可能较快。     

Diagnostic strategy for occult hepatitis B virus infection

In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as thepresence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays.Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this ...