乙型肝炎患者胆囊黏膜中病毒抗原表达分析

目的通过对慢性乙型肝炎患者的胆囊组织进行HBsAg、HBcAg的检测,了解乙型肝炎病毒在胆囊黏膜组织中的定位及分布状况以及对胆囊功能的影响,探讨慢性乙型肝炎患者胆囊病变与乙肝病毒（HBV）感染的关系.方法以鼠抗-HBs单克隆抗体、兔抗-HBc多克隆抗体,采用免疫组化S-P（SP）法,检测胆囊黏膜组织中的HBsAg和HBcAg.血清乙型肝炎病毒感染标志物阳性患者石蜡包埋胆囊标本29例为研究对象,血清乙型肝炎病毒感染标志物检测阴性患者的胆囊标本12例为对照组.乙肝病毒血清学检查用ELISA法检测.结果（1）乙型肝炎患者胆囊黏膜中存在HBsAg和HBcAg,29例患者胆囊黏膜组织中HBsAg的检出率为37.9%（11/29）,HBcAg的检出率为20.68%（6/29）.对照组HBsAg和HBcAg各有1例阳性,阳性率为8.3%（1/12）,HBsAg主要呈弥漫胞浆型分布,光镜下呈棕黄色颗粒沉积,主要分布在胆囊黏膜上皮细胞中,HBcAg的分布呈胞浆型和核型两种形态,见于腺上皮细胞和成纤维细胞中;（2）HBV病毒抗原阳性组和阴性组均呈慢性炎症性改变,胆囊黏膜组织的病理改变无明显差异;（3）胆囊息肉与HBV病毒感染的关系密切,肝癌患者的癌旁组织和胆囊黏膜中病毒抗原表达明显.结论乙型肝炎病毒感染者的胆囊黏膜中存在HBV病毒抗原,提示乙型肝炎病毒在肝外组织胆囊黏膜中也存在感染.     

乙型肝炎病毒e抗原阴性重型肝炎病人前C基因信号酶位点变异

为进一步了解乙型肝炎病毒变异所致肝细胞内过度表达乙型肝炎病毒ｅ抗原（ＨＢｅＡｇ）前体对肝细胞可能带来的影响，用聚合酶链反应（ＰＣＲ）产物直接和克隆后序列分析，在中国ＨＢｅＡｇ阴性重型肝炎病人中发现一种新ＨＢＶ变异株：前Ｃ区第１７位密码子由缬氨酸变为苯丙氨酸，变异影响信号酶切功能，导致ＨＢｅＡｇ加工和分泌障碍，ＨＢｅＡｇ前体在肝细胞内过度积聚。认为细胞毒Ｔ淋巴细胞攻击此靶抗原可能是肝细胞严重坏死的原因，但因例数太少尚难肯定。     

Hepatitis B Virus Vaccine for Patients with Hepatitis C Virus Infection

Summary Hepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection. Received: December, 1999 · Revision accepted: July 1, 2000     

当今慢性乙型肝炎治疗实践对HBV核酸检测方法的新需求

乙型肝炎病毒感染引起的慢性乙型肝炎仍是威胁我国人民生命健康的重要问题.当前治疗慢性乙型肝炎以口服恩替卡韦、替诺福韦和丙酚替诺福韦等高耐药屏障的一线核苷(酸)类似物为主,可强效抑制病毒复制,减少肝硬化和肝细胞癌的发生率.然而当前临床实践中,在启动治疗、监测疗效及判定停药等方面,均存在一定困难或争议.实现慢性乙型肝炎的"精...     

Hepatitis B virus in the Arab world: Where do we stand?

The epidemiology of viral hepatitis is of great importance for planning and managing health provision for all the countries in the Arab world. However, data on viral hepatitis are not readily available in a large percentage of Arab countries. Hepatitis B virus (HBV) is considered to be one of the most important causes of chronic hepatitis, cirrhosis and hepatocellular carcinoma. A systematic electronic search of published literature was conducted to extract data on epidemiology and risk factors for the analysis of HBV infection among the countries in the Arab world.The prevalence of chronic HBV infection was found to be decreasing in some Arab countries although it was still unacceptably high. This was particularly evident in the Arabian Gulf region, in Lebanon, Egypt and Libya. The age-specific prevalence varied from country to country with decline in prevalence being noted among children in the Gulf States and among Libyan women. These declines in prevalence are most likely to be related to the Expanded Immunization Programme.The alarmingly high prevalence of chronically infected patients in some areas and the widespread differences in HBV prevalence between Arab nations may be explained by the variation in risk factors involved. This situation calls for targeted approaches to tackle HBV-related mortality and morbidity. Precise HBV infection prevalence data are needed at the national and the sub-national level to estimate the disease burden, guide health intervention programmes and evaluate vaccine efficiency.     

肝移植术后乙型肝炎复发的处理——13例分析

目的总结和探讨乙型肝炎相关终末期肝病肝移植术后乙型肝炎复发的处理方法。方法回顾性分析我院13例肝移植术后患者发生乙型肝炎再感染或复发后的处理措施及疗效。结果13例患者分别采取拉米夫定改为阿德福韦、恩替卡韦或加大乙型肝炎免疫球蛋白用量的方法,其中5例HBsAg经治疗后转阴,5例HBsAg明显下降,总有效率76.9%。结论肝移植术后HBIG、恩替卡韦、阿德福韦能不同程度控制肝移植术后乙型肝炎复发。     

Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B

1. Download : Download high-res image (184KB)
2. Download : Download full-size image

     

Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin's lymphoma

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.     

乙肝患者外周血单个核细胞中乙肝病毒复制中间体RNA与乙肝病毒DNA相关性的研究

采用逆转录－多聚酶链反应（RT－PCR）技术检测乙肝患者外周血单个核细胞（PBMCs）乙肝病毒复制中间体RNA（HBV RNA）,60例乙肝患者5例PBMCs中HBV RNA阳性,26例PBMCs中HBV DNA阳性,27例血清HBVDNA阳性;PBMCs HBVDNA 阳性患者中有4例PBMCs HBV RNA阳性,血清HBV DNA阳性患者中有3例PBMCs HBVRNA阳性;17例血清HBeAg阳性患者中有4例PBMCs HBV RNA阳性。血清HBeAg、HBV DNA及PBMCs中HBV DNA阴性患者,其PBMCs HBV RNA仍可能阳性,其PBMCs可成为乙肝患者肝病复发和传播的来源。     

肝纤维化血清学指标与乙型和丙型肝炎关系的临床流行病学分析

目的评价血清HA,LN,PⅢP,IV-C联检在乙型和丙型肝炎肝纤维化诊断中的价值,分析乙、丙型急性肝炎转为慢性的变化情况。方法157例乙型肝炎和47例丙型肝炎和40例健康成人组采用ELISA法测定4项肝纤维化血清学指标。结果HA,LN,IV-C 3项指标明显高于健康成人组,各组间的检测指标水平随肝病组织炎症程度而增高;慢性丙型肝炎阳性检出率明显高于急性丙型肝炎,慢性乙型肝炎阳性检出率与急性乙型肝炎相近。结论3项指标联合应用对肝纤维化程度的判断有诊断价值;丙型肝炎比乙型肝炎更容易转化为慢性。     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

目的 检测HBV核心启动子区(CP)基因变异方式.方法 自HBV慢性感染患者血清中提取HBV DNA,扩增CP区域序列,克隆入pMD19 T载体,选择阳性克隆进行DNA测序,与已知HBV基因相应序列比较患者体内HBV基因变异位点以及变异形式.结果 自21例患者中共挑选74个克隆测序,54个克隆中病毒基因序列CP区发生大段缺失突变,长度达234个核苷酸,另有1个克隆发生245个核苷酸缺失突变.缺失突变区域包括CP区、HBeAg起始密码子和直接重复序列(DR)Ⅰ区,命名为CP缺失突变,发生CP缺失突变的病毒株同时存在A1585T替换突变,这两个部位的突变具有联动特征.结论 观察到一种导致HBeAg阴性慢性乙型肝炎的新方式,即CP、HBeAg起始密码子缺失突变,并提出一种简明的CP缺失检测方式.     

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   

拉米夫定耐药突变相关慢性重型乙型肝炎27例分析

目的 研究在拉米夫定治疗慢性乙型肝炎的过程中出现拉米夫定耐药突变相关的慢性重型乙型肝炎的临床特点.方法 回顾性分析27例在拉米夫定治疗过程中出现耐药突变的慢性重型乙型肝炎病例,分析其临床特征,用基因芯片法或基因测序法检测YMDD突变类型,对8例施行肝移植术后的离体肝组织分析其病理特点.采用χ2检验进行统计学分析.结果 27例拉米夫定耐药患者的YMDD突变类型分别为:YVDD突变5例,YVDD突变+L180M突变2例,YIDD突变13例,YIDD+L180M突变4例,YVDD突变+YIDD突变1例,YVDD突变+Y1DD突变+L180M突变2例,单独L180M突变未检出.根据治疗前是否存在肝硬化,分为肝硬化组和非肝硬化组.与肝硬化组相比,非肝硬化组慢性重型乙型肝炎的发生率低,预后好,年龄小,HBeAg阳性率高.8例离体肝组织病理分析显示两种主要病理类型,一种主要表现为活动性肝硬化,另一种为大块或亚大块坏死,肝脏显著萎缩.结论 肝硬化为拉米夫定耐药突变相关的慢性重型乙型肝炎的高危因素.拉米夫定耐药突变相关的慢性重型乙型肝炎可能存在两种发病机制.     

Body surface area is an independent factor contributing to the effects of lamivudine treatment

Background:

It has been suggested that lamivudine therapy may be even more effective if administered at higher doses than is dictated by the current standard regimen. We analyzed the correlation between the effects of lamivudine and body surface area (BSA).

Method:

We evaluated 134 patients with chronic hepatitis B who had been treated with lamivudine for more than 12 months. The effect of the treatment was evaluated from the levels of serum alanine aminotransferase (ALT) and HBV-DNA. Several variables that could influence the response to treatment, including ALT, albumin, and bilirubin levels, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed.

Results:

Univariate logistic analysis selected platelet counts, BSA, HBV-DNA and HBeAg in the biological evaluation, and bilirubin, BSA, HBV-DNA and HBeAg in the virological evaluation (χ² > 1.0). Using these factors, multivariate analysis revealed that BSA (χ² = 12.8, p = 0.0004) was the only factor that could contribute significantly to the improvement of ALT levels, and that BSA (χ² = 4.4, p = 0.0354) and HBeAg (χ² = 8.1, p = 0.0044) were independent factors that could influence the suppression of HBV-DNA.

Conclusion:

We revealed that BSA is a significantly predictor of the effect of lamivudine therapy, suggesting that lamivudine dosage should be based on the individual BSA.     

献血员隐匿性乙型肝炎病毒感染的分子流行病学

目的 了解献血员中隐匿性HBV感染的发生率,从S基因变异角度探讨隐匿性HBV感染可能的分子机制.方法 收集经血站筛查HBsAg阴性的合格献血员血浆594份,ELISA法检测HBV血清学标志物,套式PCR检测血清HBV DNA.对筛查出的隐匿性HBV感染者再次用雅培试剂定量检测HBV血清学标志物,并对其S区进行测序,发现可能与HBV隐匿性感染有关的变异位点.随机收集11例HBsAg阳性的HBV感染者作为阳性对照,对其S区进行测序,比较其与隐匿性HBV感染之间的关系.结果 在594例献血员中有15例为隐匿性HBV感染,隐匿性HBV感染的发生率为2.5％.未发现HBV血清学标志物检测结果与隐匿性HBV感染有相关性.15例隐匿性HBV感染者中有10例进行了S区测序,结果HBV均有不同程度的变异,其中3例在“a”决定簇内出现氨基酸突变,分别为1126T(1例)、T140I(2例).与隐匿性HBV感染者相比,阳性对照在“a”决定簇内仅出现了1例T131N变异.结论 常规检测HBsAg阴性的献血员中存在隐匿性HBV感染,且这些病毒可能存在变异.     

未经治疗的慢性乙型肝炎患者乙型肝炎病毒耐药变异、基因型和血清型研究

目的 研究未经核苷(酸)类似物(NA)治疗的慢性乙型肝炎患者HBV耐药变异、基因型、基因亚型和血清型特点.方法 从北京大学附属医院收集97例未经NA治疗的慢性乙型肝炎患者血清,用半巢式聚合酶链反应-直接测序法获得HBV全长逆转录酶区序列,用生物信息学技术筛查该区内11个经典耐药变异位点并鉴定基因型、基因亚型和血清型.用统计分析软件SPSS11.0进行t检验和χ~2检验. 结果 HBV在11个经典耐药变异位点上均为野生型氨基酸;B基因型和C基因型分别占36.1%(35/97)和63.9%(62/97),前者均属B2亚型,后者C2亚型占91.9%(57/62),C1亚型占6.5%(4/62),1例未能分出亚型.已知出生地的患者中,71.9%(23/32) B基因型感染者出生于我国南方地区,81.6%(40/49) C基因型感染者出生于北方地区,基因型地域分布特点明显,χ~2=23.19,P<0.01.血清型为adr者占60.8%(59/97),与C基因型相关;为adw者占38.1%(37/97),与B基因型相关,χ~2=87.83,P<0.01.结论 未经NA治疗的慢性乙型肝炎患者体内野毒株为优势株,其基因型、基因亚型和血清型与患者出生地有关.     

乙型肝炎病毒前S2序列异质性的初步研究

目的 通过对乙型肝炎病毒（HBV）前S2基因序列的研究,证实HBV在慢性感染者中以准种状态存在,并对前S2序列异质性进行初步的阐明。方法 以中国株HBV基因序列为依据,设计特异性PCR引物,自51例慢性HBV感染患者血清中扩增HBV前S2基因序列,采用聚丙烯酰胺凝胶电泳技术展示缺失突变,随机选择克隆测序,确定病毒的变异程度。结果 聚丙烯酰胺凝胶电泳结果发现,52.9%（27／51）患者血清中可获得2或3条扩增条带;测序结果发现前S2基因序列存在缺失突变高发区,氨基酸序列分析示缺失突变主要位于前S2编码蛋白的氨基端。结论 HBV前S2序列内有一缺失高变区,并在患者体内表现为多种变异形式;氨基端附近的变异可能影响中和抗体的识别作用。结果提示HBV慢性携带者体内有HBV准种共存。