乙型肝炎病毒感染的免疫反应

乙型肝炎病毒 (HBV)在成年人感染后大多被清除 ,而母亲通过垂直传染途径 ,常导致儿童HBV持续性感染。HBV感染的预后取决于宿主与病毒间的相互作用。本文阐述了急性自限性肝炎及慢性肝炎的免疫反应 ;不同免疫反应对病毒复制及肝损伤产生的不同影响及免疫学治疗的有关展望。一、急性自限性肝炎的免疫反应及发病肝脏内包含NK细胞 ,自然杀伤T细胞 (NKT) ,库普弗细胞等天然免疫细胞。这些细胞能快速分泌一系列抗炎细胞因子 ,它们有抗病毒的效果 ,活化和维持先天免疫反应 ,启动抗原特异性的免疫反应等。任何病毒感染 ,被感染细胞本身在抵御…     

慢性乙型肝炎病毒感染及其防治

慢性乙型肝炎病毒(HBV)感染一般是指血清乙型肝炎表面抗原(HBsAg)持续阳性6个月以上。2000年美国国立卫生研究院慢性乙型肝炎防治研讨会将慢性HBV感染分为3期，即免疫耐受期、慢性乙型肝炎期和非活动性或无症状HBV携带期。     

慢性乙型肝炎重叠戊肝病毒感染41例临床分析

乙型、戊型肝炎病毒重叠感染的临床表现及转归与其单一乙型或戊型肝炎病毒感染不同.我们回顾性分析了近年收治的41例该病患者的流行病学、临床特点及转归等资料,现报道如下.     

胸腺肽治疗慢性乙型肝炎病毒感染疗效评价

[ChanHL ,TangJL ,TamW ,etal .TheefficacyofthymosininthetreatmentofchronichepatitisBvirusinfection :ameta analysis .AlimentPharmacolTher,2 0 0 1,15 ( 12 )∶1899～90 5 ]胸腺肽治疗慢性乙型肝炎病毒感染的试验规模小且结果不一致。为评估胸腺肽在慢性乙型肝炎病毒感染治疗中的确切功效,从MEDLINE ,EMBASE及Cochrane临床试验记录中选取持续2 4周使用胸腺肽和安慰剂(或普通治疗)比较治疗慢性乙型肝炎病毒感染的随机对照试验。采取intention to treat的方法分析生化(转氨酶正常化)和病毒学(乙型肝炎病毒DNA和乙型肝炎e…     

TT病毒感染对慢性乙型肝炎的影响

探讨TT病毒感染对慢性乙型肝炎病情的影响。采用巢式聚合酶链反应检测血清中的TTV-DNA和HBV-DNA。用ELISA法检测血清中HBV标志物。在125例慢性乙型肝炎患者中,检测出TTV-DNA阳性者15例,占总检测血清的12.O％。重叠感染者中,慢性轻度2例(13.33％),慢性中度6例(40.00％),慢性重度7例(46.47％)。未重叠TTV感染的110例慢性乙肝中,轻度84例(76.36％),中度12例(10.91％),重度14例(12.73％)。两组比较均有显著性差异(P相似文献   

乙型肝炎病毒感染与冠心病的关系研究

动脉粥样硬化 (AS)是冠心病 (CHD)的主要病理改变。近 1 0年来 ,众多的临床病理与流行病学研究结果表明 ,除了传统的CHD的致病因素如吸烟、高血压、高脂血症、糖尿病等外 ,感染与AS及CHD的发生发展有关。近年的研究表明 ,幽门螺杆菌、肺炎衣原体、巨细胞病毒、单纯疱疹病毒在内的多种病原微生物可能是致AS与CHD的感染因素〔1〕。乙型肝炎病毒 (HBV)作为一种病原微生物 ,其与AS及CHD的相关性所知甚少 ,曾有报道乙型肝炎病毒表面抗原 (HBsAg)阳性的患者颈动脉粥样斑块的检出率明显增高〔2〕,但其与CHD的相关性笔者尚未见报道。阐…     

乙型肝炎病毒感染模型研究新进展

病毒性肝炎抗病毒药物的开发和评价中的重要环节之一就是建立一种方便有效的体内外模型。现就乙型肝炎的感染模型新进展作一简要综述。 一、体外模型 乙型肝炎病毒(hepatitis B virus,HBV)感染有高度的种属和组织特异性,它只感染人和类人猿。其原因是病毒黏附以及病毒DNA转录及复制对细胞有严格的要求。体外培养的     

乙型肝炎病毒感染基因治疗的进展

利用基因技术治疗慢性乙型肝炎病毒感染的研究进展迅速,如反义寡核苷酸、核糖核酸酶及显性失活突变体等。本文就这些技术近年来在抗HBV方面的研究进展进行综述。     

女性慢性乙型肝炎病毒感染的临床特点

通常认为慢性乙型肝炎病毒（HBV）感染是一个发病率存在性别差异的疾病,更多见于男性。梁晓峰等报道HBsAg阳性率在男性为8．12％,而在女性约6．85％。为了解我国现阶段慢性HBV感染者中女性的比例及其临床特点,我们调查了我院2005年住院的慢性HBV感染2381例。     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点

目的探讨新疆维吾尔族慢性乙型肝炎患者HBV基因型分布及其特点。方法采用型特异性引物巢式PCR法对127例维吾尔族慢性乙型肝炎患者进行基因分型,并测序验证。结果基因D型占39．4%（50/127）,基因B型占22．0%（28/127）,基因C型占16．5%（21/127）,基因BD混合型占9．4%（12/127）,基因CD混合型占8．7%（11/127）,基因BCD混合型占3．9%（5/127）; HBeAg阳性与HBeAg阴性的维吾尔族慢性乙型肝炎患者基因型分布,差异无统计学意义（x^2= 6．033,P＞0．05）;不同年龄维吾尔族慢性乙型肝炎患者HBV基因型分布差异无统计学意义（x^2= 3．137,P＞0．05）;不同性别维吾尔族慢性乙型肝炎患者HBV基因型分布差异亦无统计学意义（x^2= 8．058,P＞0．05）。结论新疆维吾尔族慢性乙型肝炎患者HBV基因型以D型占优势,其次可见B、C型及BD、CD、BCD混合型。同一疾病谱的慢性HBV感染者基因型分布可能与宿主HBeAg状态、年龄、性别无明显关系。     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

Clinical profile of hepatitis B virus chronic infection in patients of Brazilian liver reference units

Purpose  

To assess data about chronic forms of hepatitis B virus (HBV) infection in Brazilian reference units, the Brazilian Society of Hepatology (SBH) performed a survey, with its associates spread throughout the country.     

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

Occult hepatitis B infection(OBI), is characterized by low level hepatitis B virus(HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen(HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.     

Measurement of hepatitis B virus core-related antigen as predicting factor for relapse after cessation of lamivudine therapy for chronic hepatitis B virus infection

Background

Prolonged lamivudine therapy has two major problems: breakthrough hepatitis during treatment and relapse of aminotransferase (ALT) after cessation of the therapy. The aim of this study was to examine factors that could predict ALT flare after stopping lamivudine therapy.

Methods

We analyzed 22 Japanese patients with chronic hepatitis B infection, in whom lamivudine therapy was stopped after HBV DNA level had been gone undetectable (<3.7 LGE/ml) during at least six consecutive months. The post-treatment followed up was carried for 28 months in median (range 9–41). HBV core-related antigen (HBcrAg) assay was assessed using newly developed assay.

Results

After cessation of lamivudine therapy, 11 patients (50%) had relapsed (reactivation of serum ALT >80 IU/l, relapsers) and remaining 11 (50%) did not relapse (non-relapsers). In the univariate comparison of relapsers versus non-relapsers, HBcrAg level at lamivudine cessation point (4.5 ± 1.0 versus 3.4 ± 0.9; p = 0.0145) has been shown as a significant predictive factor for non-relapse. All patients with HBcrAg <3.0 log U/ml at the cessation point had no ALT flares. Multivariate analysis on effects of 10 factors (age, sex, cirrhosis, pretreatment ALT level, HBV DNA level, HBcrAg level, mean months till undetectable HBV DNA, duration of undetectable HBV DNA and HBcrAg level at lamivudine cessation point), indicated that HBcrAg level at lamivudine cessation point <3.4 log U/ml was the only independent predictive factor for absence of the post-treatment relapse.

Conclusions

HBcrAg level at lamivudine cessation point might be useful as a prognostic predictor of response to lamivudine therapy cessation. The measurement of HBcrAg is a useful additional test for monitoring chronic HBV infection.     

一种新的免疫活性细胞(IPCs)在慢性乙型肝炎患者中的检测

目的近年来研究发现了一种在人的外周血中专职产生α/β干扰素的免疫活性细胞,即“干扰素产生细胞(IPCs)。IPCs在外周血中产生干扰素的量是其他产生干扰素细胞的200～1000倍。因此可以说IPCs是体内IFN的专职产生细胞。 IPCs在慢性乙型肝炎患者体内数量的多少和功能的强弱,决定着患者体内IFN的产量,并直接影响着HBV的清除和病程的转归。本文初步检测了干扰素产生细胞(IPCs)在慢性乙型肝炎患者体内的变化特点,以期进一步明确HBV持续感染的患者中是否存在着IPCs数量和功能的缺失及其对慢性肝炎发病机制的影响。方法随机选取了解放军第三○二医院2001年7月～8月住院的25例慢性乙型肝炎患者,男性19例,女性6例,年龄12～49岁。对照组14例为健康供血员。新鲜分离的抗凝外周全血3ml,用PBS等倍稀释,混合均匀后轻轻加在淋巴细胞分离液面上,血液与淋巴细胞分离液的体积比为2:3,2 500rpm离心25min,轻轻吸界面细胞到一干净离心管中,加PBS(含2％胎牛血清和0.5mMEDTA)悬浮细胞,以1500rpm、1 000rpm离心洗涤细胞2次,洗尽血小板。1×10~6PBMC用荧光标记鼠抗人CD_4-FITC,CD3,CD14,CD16,CD20和CD11c—PE单抗染色25min,1％的多聚甲醛固定,上流式细胞仪检测。按照国外Liu YJ(Blood2001,98(4):906-912)所采用的方法,在前向角和侧向角散点图中找出所有可见的PBMC,先设门R1,记数10~5个PBMC。再以PE标记的CD3,CD14,CD16,CD20,CD11c为横轴,以FITC标记的CD4为纵轴作散点图,设门2,门2内的细胞即我们所要检测的IPCs。记数门2内所有的细胞所占10~5个PBMC的百分数,然后比较慢性乙型肝炎患者和健康人外周血中IPCs数量的变化。结果 25例慢性乙型肝炎患者外周血中IPCs的百分数为0.093±0.078,较正常人(0.326±0.092)明显降低,两者相差3.5倍,有显著差异(P<0.001)。同时发现在HBV DNA(+)的患者中其IPCs的百分数为0.081±0.054,明显高于HBV DNA(-)患者(0.040±0.031),差异显著(P<0.01)。IPCs数量与慢性乙型肝炎患者ALT水平无相关性。结论本文通过检测25例慢性乙型肝炎患者和14例正常人外周血IPCs的数量发现,在慢性肝炎患者外周血中存在着明显的IPCs数量的降低,平均只占其外周血PBMC的0.093％,而明显低于正常人的0.326％(P<0.001)。因此,在临床中我们观察到慢性肝炎患者体内HBV病毒总是在潜伏或增殖,导致病情迁延反复以及在实验研究中发现患者体内IFN的量低于正常人等现象,这些现象最直接的原因可能是其体内IPCs数量的下降所致。同时我们也观察到,虽然在慢性乙型肝炎患者体内存在着IPCs数量的降低,机体的免疫反应受到抑制,但并不是机体处于无反应状态。因为在有HBV复制的病例中,其IPCs为0.081±0.054,与无HBV复制的病例组相比(0.040±0.031),P<0.05。由此可见在病毒的刺激作用下,机体自身的细胞免疫应答也是增强的,但可能由于数量上的不足而不足以抑制病毒的复制,因而HBV DNA呈阳性。本研究只是初步检测了慢性肝炎患者IPCs的数量及其临床意义,有关IPCs的研究还存在着许多待阐明的问题,例如IPCs数量和T细胞亚群变化之间的关系;IPCs水平的高低与患者HBV病毒载量动态变化以及IPCs与慢性肝炎病程之间的关系等问题,有待我们去进一步探讨。     

YMDD耐药变异与HLA等位基因多态性的相关性

目的：初步探讨慢性乙型肝炎(CHB)患者拉米夫定治疗中YMDD变异与HLA-A,B,DRB1各位点等位基因分布频率的相关性．方法：对142例CHB患者,采用荧光标记杂交双探针PCR融解曲线法(FH-PCR-MC)检测血浆HBV YMDD变异；对其中56例患者的外周血白细胞,采用序列特异性引物/聚合酶链式反应(PCR-SSP)技术检测人类白细胞表面抗原等位基因(HLA-A-B,DRB1)分型．结果：在用拉米夫定治疗的142例CHB患者中,YMDD变异率为56．3％．HLA-B~*58和DRB1~*03等位基因分布频率在YMDD变异组与YMDD野生组比较有显著性降低(0．013 vs 0．094,P=0．036；0．000 vs 0．063,P=0．024)；HLA-A~*30等位基因分布频率在YIDD组明显增高,与YVDD组比较差异显著(0．158 vs 0．024,P=0．034)；HLA-A~*33等位基因分布频率在YVDD变异组明显增高,与YIDD变异组比较差异显著(0．119 vs 0．000,P=0．028)．结论：YMDD耐药变异与HLA等位基因多态性有一定相关性．携有HLA-B~*58和DRB1~*03等位基因的个体感染的HBV可能不易发生YMDD变异；携有HLA-A~*30等位基因的个体感染的HBV可能易发生YIDD变异：携有HLA-A~*33等位基因的个体感染的HBV可能易发生YVDD变异．     

二十岁以下慢性HBV感染者HBVDNA与HBeAg的定量关系

目的:探讨20岁以下慢性乙型肝炎病毒(HBV)感染者血清中HBV DNA、乙型肝炎病毒e抗原(HBeAg)定量之间关系.方法:用实时荧光定量聚合酶链反应(FQ-PCR)及时间分辩荧光免疫分析(TRFIA)技术检测339例(1-20岁)慢性HBV感染者血清中HBVDNA、HBeAg含量,用速率法检测ALT水平.结果:HBeAg定量＞0.3 NCU/mL、HBV DNA定量＞105 copies/mL、而ALT水平正常者占总检测病例的92.3%;HBV DNA定量(对数值)与HBeAg定量之间存在正相关关系(r=0.769,P＜0.001)和线性回归关系(b=0.32,R2=0.59,P＜0.001).结论:20岁以下慢性HBV感染者血清中HBVDNA水平与HBeAg水平存在同时消长的关系,但是有极少患者例外.HBV DNA定量与HBeAg定量两种检测方法相结合应能够更客观地反映患者HBV感染状况,二者具有互补性.     

慢性乙型肝炎患者中庚型肝炎病毒检测

目的了解慢性乙型肝炎中庚型肝炎病毒（ＨＧＶ）的感染率及其对病变程度和ＨＢＶ复制的影响。方法逆转录聚合酶链反应（ＲＴＰＣＲ）检测６５例经肝活检证实的慢性乙型肝炎患者血清中ＨＧＶＲＮＡ。结果有８例（１２．３％）慢性乙型肝炎患者合并ＨＧＶ感染,轻度、中度和重度患者中的ＨＧＶ检出率统计学处理差异无显著性,ＨＧＶ混合感染与其临床表现无相关性,ＨＧＶ阳性组与阴性组患者的肝功能改变相近。ＨＢｅＡｇ阳性组和ＨＢｅＡｇ阴性组患者的ＨＧＶ检出率亦相当。结论在慢性乙型肝炎患者中,ＨＧＶ混合感染对慢性乙型肝炎的病变程度及病毒复制无明显影响