混合庚型肝炎病毒感染对慢性乙型肝炎患者HBV复制的影响

研究表明 ,庚型肝炎病毒 (ＨＧＶ )与乙型肝炎病毒(ＨＢＶ)混合感染的现象常见。然而混合ＨＧＶ感染对ＨＢＶ复制影响的研究 ,报道较少。我们应用逆转录 聚合酶链反应 (ＲＴ ＰＣＲ)方法对 2 2 3例慢性乙型肝炎 (ＣＨＢ)患者血清进行了ＨＧＶＲＮＡ检测 ,并采用定性、定量ＰＣＲ技术、免疫组织化学 (免疫组化 )技术等对ＨＧＶＲＮＡ阳性与阴性患者进行了对比研究。材料与方法一、研究对象2 2 3例ＣＨＢ均为 1997～ 1999年间收治的住院患者 ,其中男 16 9例 ,女 5 4例 ,平均年龄 33.3岁 ,其中ＨＧＶＲＮＡ阳性患者 37例、阴性患者 186例 ,两…     

乙型肝炎病毒感染、纤溶状态、炎症因子与肝脏疾病进展的关系

HBV感染引起的慢性疾病是我国主要的传染病。5年随访研究表明，慢性乙型肝炎患者肝硬化发生率为2％～20％，代偿性肝硬化发展为失代偿性肝硬化发生率为20％～23％，发展为肝细胞癌者为6％～15％^[1]。肝细胞的代偿能力非常强，肝脏损伤后，肝功能检测一般皆在正常范围，所以肝脏的损伤早期很难发现^[2]。本研究对无肝病史的肝组织进行HBV蛋白和核酸检测，     

乙型肝炎病毒感染对肾移植患者预后的影响

终末期肾功能衰竭(ESRF)患者乙型肝炎病毒(HBV)的高感染率给肾移植(RT)领域带来一系列的临床问题。主要表现在：①HBV导致RT受者肝硬化、肝癌和肾脏损害，影响RT受者人、肾存活率；②免疫抑制剂可以改变HBV感染进程；③HBV阳性供肾应用方面的矛盾等等。本文就近年来这些问题的研究进展作一综述。     

乙型肝炎病毒感染、复制及其清除机制

一、乙型肝炎病毒（HBV）感染、复制与表达 1.HBV感染肝细胞等宿主细胞机制:HBV进入细胞是由其包膜蛋白介导的,该包膜蛋白是由S基因区（分pre-S1、pre—S2和S区）编码的大蛋白（LP）、中蛋白（MP）和小蛋白（SP）按一定的比例和方式装配而成的复合物。HBV包膜蛋白成分与肝细胞等宿主细胞膜上相应的受体特     

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。     

慢性乙型肝炎病毒感染的处理

最近美国著名肝病专家Keeffe教授和Schiff等其他一些教授就慢性乙型肝炎病毒(HBV)感染在临床处理中的检测方法、治疗对象、治疗时机、疗程和方法、治疗过程中如何监测病人等一系列问题提出了指导性建议,简要介绍如下。     

乙型肝炎病毒复制对慢性乙型肝炎病情的影响

研究旨在了解乙型肝炎病毒(HBV)复制对慢性乙型肝炎(简称慢乙肝)患者病情的影响。     

隐匿性乙型肝炎病毒感染研究进展

血清HBs Ag阴性,但肝组织或血清HBV DNA长期存在,这种状态被称为隐匿性HBV感染(OBI)。由于实际HBV流行率和病毒流行株的地域性差异、所选取的研究人群的差异和不同检测方法的敏感性和特异性的差异,不同研究所得到的OBI的流行率有很大的差别。OBI的形成机制尚未完全阐明,可能有多种病毒学因素、宿主因素参与其中。OBI能通过输血、分娩和肝移植等方式进行传播,引起新发感染。当宿主免疫功能下降或应用免疫抑制性药物时,OBI可以复燃,恢复经典的血清学表现。OBI引起的轻微但持续的坏死性炎症可以促进肝脏疾病的进展,并且可以通过直接或者间接的机制增加肿瘤的发生风险。临床上需要建立更敏感的检测方法诊断OBI,以减少OBI相关的潜在威胁,帮助医师合理采取治疗措施,延缓病情进展。     

慢性乙型肝炎抗病毒治疗进展

据统计，全世界范围内大约有4亿乙型肝炎病毒(HBsAg)感染者，我国是高发区，据最新统计资料显示，HBsAg阳性者占人口总数的9．75％，约1．3亿。慢性乙型肝炎患者大约为3000万，其中10％-20%可以演变为肝硬化，1％～5%可发展为肝癌。HBV虽然对肝细胞无直接致病变作用，但是病毒可以通过诱发免疫反应而引发细胞水肿、坏死或凋亡等多种机制介导对肝细胞的损伤。HBV的长期持续性复制，     

Viral replication in chronic hepatitis B virus infection

Digestive Diseases and Sciences -     

Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication.

Serum and liver HBsAg bear an inverse relation to each other during the evolution of chronic hepatitis B virus infection and the quantity of HBsAg in tissue rises gradually with time. In this study, intracellular and extracellular levels of HBsAg were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis B virus infection to determine a possible relationship with hepatitis B virus replication. Serum levels of HBsAg correlated with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.005, and tissue HBcAg, p less than 0.02) but inversely with tissue HBsAg (p less than 0.05). In similar fashion, in vitro export of HBsAg was also related to the presence of active viral replication markers (serum hepatitis B virus DNA, p less than 0.02, and tissue HBcAg, p less than 0.05) and negatively with tissue HBsAg (p less than 0.001). Export of HBeAg also correlated positively with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.05 and tissue HBcAg, p less than 0.05). Further experiments indicated that intrahepatic pre-S1 and pre-S2 correlated closely with intrahepatic HBsAg, indicating that a failure to export HBsAg was unlikely to be attributable to deficient intracellular expression of pre-S1 or pre-S2. These data indicate that in vitro primary hepatocyte culture of hepatitis B virus-infected cells provides an accurate reflection of in vivo export of HBsAg and that this is closely related to the presence of active viral replication.     

Virus replication and liver disease in chronic hepatitis B virus infection

Recent studies on the natural history of chronic hepatitis B virus infection have provided evidence for a close temporal relationship between the phase of active virus replication and development of liver lesions. To assess the role that virus replication plays in this phase in determining the severity of the liver disease, we studied serum levels of virus-specific DNA-polymerase activity and hepatitis B_e antigen/antibody status in 48 chronic carriers of the hepatitis B surface antigen found positive for the hepatitis B core antigen in the liver. There was a remarkably evident inverse correlation between virus replication activity and liver disease activity, patients with minimal histological changes having the highest DNA-polymerase levels (mean±sd: 3879±2557 cpm) and those with severe chronic active hepatitis the lowest enzyme levels (419±246 cpm), while cases of chronic persistent hepatitis and of mild chronic active hepatitis had intermediate levels. Serum hepatitis B_e antigen was detected in 31/32 patients with milder liver lesions and in 11/16 with severe liver lesions; the remaining five cases were anti-HB_e-positive despite the presence of the core antigen in the liver. Serum levels of virus replication markers closely correlated with the distribution pattern of the core antigen in the liver. These findings indicate that in chronic hepatitis B the severity of liver disease is not directly related to levels of virus replication, thus suggesting a predominant role of host immune mechanisms.     

HBsAg/PRE-S2 expression of viral replication and hepatic inflammation in chronic hepatitis B virus infection

A close relationship (r = 0.186, P less than 0.025) was found between the serologic level of HBsAg/pre-S2, an envelope protein of hepatitis B virus, and the level of viral replication expressed by HBeAg. The rate of co-appearance and co-absence of both pre-S2 and HBeAg was 75.0%. Among HBeAg-positive cases, the prevalence of pre-S2 and its serologic level were significantly higher during exacerbation than resolution of chronic active hepatitis (73.3 vs 33.3%, 111.4 vs 1.4 ng/ml), and also higher than those among HBeAg-negative cases. Those the prevalence and the level were also higher in chronic active hepatitis than in chronic asymptomatic carriers (26.9 vs 11.5%, 2.95 vs 0.49 ng/ml). Pre-S2 prevalence in the group with highest scoring of histological activity was significantly higher than that in the groups with lower scoring (88.9 vs 40.0 and 36.4%) and the serologic level of pre-S2 also increased along with the scoring. Those data suggest that pre-S2 was associated with hepatic inflammatory activity as well.     

Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection

Approximately 20% of patients with hepatitis B virus (HBV) infection may experience extrahepatic disease. These manifestations include a viral prodrome with a serum sickness-like syndrome, polyarteritis nodosa, glomerulonephritis, as well as various neurological and dermatologic diseases amongst other manifestations. The viral pathogenesis is not well understood and has been difficult to study due to the lack of an animal model of HBV-related extrahepatic disease. Deposition of immune complexes and activation of the complement cascade has been most widely studied. However, circulating immune complexes are physiologic and occur more frequently than extrahepatic disease. Also, HBV-related extrahepatic syndromes occur in the absence of immune complex formation. Several studies support the notion that HBV replication in extrahepatic tissues may also precipitate disease but extrahepatic replication has commonly been observed without any apparent cytopathic or immune related tissue damage. It is clear that suppression of viral replication with antiviral therapy or spontaneous viral clearance positively correlates with resolution of extrahepatic disease. The use of continuous immunosuppressive therapy has largely been abandoned with the advent of robust antiviral strategies to manage disease. These data support the notion that a combination of factors including inadequate clearance immune complexes and viral replication in extrahepatic tissues play an important role in the pathogenesis. This conceptual framework is potentially significant as it emphasizes the importance of antiviral treatment in the management of extrahepatic disease.     

Detection of hepatitis B virus antigens in liver tissue. A relation to viral replication and histology in chronic hepatitis B infection

The expression of hepatitis B virus antigens was studied by double staining liver tissue with appropriate antisera and correlated with serum hepatitis B viral DNA and histology in 28 patients with disease related to chronic hepatitis B virus infection. The cellular localization of hepatitis B core and hepatitis B e antigens generally coincided, but there were important differences at a subcellular level. Thus, hepatitis B e antigen was detected in nuclei and/or cytoplasm but strong cytoplasmic hepatitis B e antigen was associated with a high serum hepatitis B viral DNA (P = 0.0017) but not with active liver disease. Hepatitis B core antigen could also be detected in nuclei and/or cytoplasm, but strong cytoplasmic hepatitis B core antigen expression, exceeding that of hepatitis B e antigen, was associated with active liver disease (P = 0.041) and not with serum hepatitis B virus DNA. The proportion of hepatocytes expressing hepatitis B surface antigen correlated inversely with the serum titer (P = 0.0017), whereas hepatitis B surface and nucleocapsid antigens were usually expressed independently. The data support the hypothesis that cytoplasmic hepatitis B core antigen and not hepatitis B e antigen is the target for immune system-mediated cytolysis of hepatocytes. Cytoplasmic hepatitis B e antigen is not associated with liver damage but is instead associated with high levels of hepatitis B virus replication.     

乙型肝炎病毒前S1蛋白在血清学诊断乙肝病毒复制中的研究

目的：探讨前S1蛋白（Pre—S1）在血清学诊断乙肝病毒复制中的意义。方法：选择慢性乙型肝炎患者血清250例。分别测定每份患者血清中HBV标志物、前S1蛋白和HBV DNA。结果：HBeAg（＋）组中前S1蛋白阳性率97．2％（70／72）,HBV DNA阳性率100％（72／72）。HBeAg（-）组中前S1蛋白阳性率60．1％（107／178）,HBV DNA阳性率63．5％（113／178）。前S1蛋白和HBV DNA的总符合率为89．6%（224／250）,2者差异无统计学意义（P〉0．05）。HBeAg和HBV DNA的总符合率为54．8％（137／250）,2者差异有统计学意义（P〈0．01）。HBsAg（-）中检出前S1蛋白阳性2例。结论：前S1蛋白比HBeAg更敏感地反映HBV复制情况,且可弥补由于HBsAg基因编码区突变造成的漏诊。     

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.