减毒水痘病毒对乙型肝炎病毒复制的影响

目的观察减毒水痘病毒对乙型肝炎病毒复制的影响。方法分别用减毒水痘病毒接种鸭乙型肝炎模型和HepG22.2.15细胞,以斑点杂交和EIA方法分别检测鸭血清中DHBVDNA和细胞培养上清液中HBsAg、HBeAg的含量。结果减毒水痘病毒两个剂量组均显示鸭血清病毒量下降,200pfu/kg组在给药后第10天和停药5d时,DHBVDNA吸光度（A）平均值分别由给药前1.17±0.29降至0.59±0.45和0.21±0.21,相比差异有显著性（t＝3.51,P＜0.01和t＝7.54,P＜0.001）;400pfu/kg组在给药后第5、10天DHBVDNA无下降,停药5d时DHBVDNAA平均值由给药前0.70±0.25降至0.32±0.17,差异有显著性（t＝3.58,P＜0.01）;减毒水痘病毒对2.2.15细胞分泌HBeAg、HBsAg均有抑制作用,最大抑制率分别为61%和33%,对HBeAg的抑制较HBsAg强。结论减毒水痘病毒在鸭乙型肝炎模型上可以显著降低血清DHBVDNA水平;在体外能够直接抑制2.2.15细胞分泌HBsAg、HBeAg,提示该病毒可能对乙型肝炎病毒复制有干扰或抑制作用。     

乙醇对乙型肝炎病毒转基因小鼠病毒复制和基因表达的影响

乙型肝炎病毒(HBV)在体内的持续感染、复制和基因表达是急、慢性乙型肝炎发病机制的重要环节。嗜酒明显影响乙型肝炎的预后，使其易于重型化、慢性化，且肝癌发生率升高。嗜酒与HBV感染对肝脏损伤有协同作用。本研究旨在通过对HBV转基因小鼠的乙醇干预，探讨它对HBV复制和基因表达的影响及其机制，以利于对乙型肝炎及酒精相关性肝病的防治。     

乙型肝炎病毒基因变异对慢性乙型肝炎患者病情发展及抗病毒治疗的影响

目的 探讨乙型肝炎病毒(HBV)基因变异对慢性乙型肝炎(慢乙肝)患者病情发展、严重程度以及对抗病毒治疗疗效的影响。方法 采用基因芯片技术，对选取的部分乙型肝炎患者进行HBV基因变异位点的检测。结果 α-干扰素治疗24周以上，HBeAg不发生血清转化，或出现HBeAg(-)／抗-HBe( )，但HBV—DNA定量检测仍持续阳性患者与nt1896、nt1814、nt1762、nt1764位点突变有关；拉米夫定治疗后，HBV—DNA先下降或转阴，后又再度反弹患者与aa528、aa552变异(即YMDD变异)造成拉米夫定耐药有关；拉米夫定治疗52周以上的部分患者易发生YMDD变异(26．4％)；在慢性乙肝患者中nt1896位点变异较普遍(68．5％)；慢性重症肝炎、肝硬化失代偿、原发性肝癌与nt1896、nt1762、nt1764位点突变亦有关。结论 HBV基因变异可加重患者病情，影响抗病毒治疗效果。临床上通过对乙肝患者进行HBV常见变异位点进行检测，对判断疾病预后，调整抗病毒治疗方案具有一定的参考价值。     

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     

慢性乙型肝炎病情反复与HBV复制标志含量的关系

本文叙述了慢性乙型肝炎病毒感染病情反复发作与其血清乙型肝炎病毒含量之间的关系。     

庚型肝炎病毒感染对乙型肝炎病毒复制的影响

肝炎病毒的混合感染,常可出现病毒间的干扰现象。庚型肝炎病毒(HGV)是1995年底Simons等、Linnen等首先报道的一种与人类肝炎相关的RNA病毒,病毒学和流行病学研究资料业已表明,HGV与乙型肝炎病毒(HBV)混合感染的现象是十分常见的。然而混合感染时HGV对HBV复制的     

核苷类药物治疗慢性乙型肝炎的新进展

据WHO统计,全球有近20亿人被乙型肝炎病毒(HBV)感染,其中约有3.5亿人为HBV慢性感染者,中国占1/3。每年约有120万HBV感染患者死于HBV相关疾病,所以寻找有效的治疗乙型肝炎药物成为当务之急。慢性乙型肝炎的关键治疗是抗HBV治疗,核苷类药物可以直接抑制HBV复制,它包括嘧啶类的拉米夫定、恩曲他滨、克拉夫定,以及嘌呤类的阿德福韦酯、恩替卡韦等。目前核苷类药物发展迅速,为此就目前进入临床和正在研发的部分核苷类药物的研究进展作一综述。1嘧啶类核苷类似物1.1拉米夫定(lamivudine,LAM)拉米夫定是目前应用范围最广的核苷类抗HBV药…     

替比夫定治疗慢性乙型肝炎的应用

口服核苷(酸)类抗病毒药的研发成功,是慢性乙型肝炎(简称:慢乙肝)治疗上的一个里程碑,激发了众多研究者和制药工业的极大关注。迄今为止,已有4种药物被批准治疗慢乙肝,另外3~4种药物在等待批准。替比夫定(简称:LdT)是最近批准的抗HBV药物,它具有明显抑制HBV复制的活性,为治疗慢     

慢性乙型肝炎患者体内乙型肝炎病毒准种特点的初步研究

一、资料与方法1.血清来源和ＤＮＡ分离 :血清来源 :其一为乙型肝炎肝硬化患者 ,其二为病毒性肝炎患者 ,均为女性 ,临床检测ＨＢｓＡｇ、ＨＢｅＡｇ、抗 ＨＢｃ阳性。其他肝炎病毒标志检测阴性。静脉采血 5ｍｌ,提取血清中的ＤＮＡ。2 .ＰＣＲ扩增目的片段 :以Ｇａｎ等[1] 发表的序列为依据 ,参照其他ａｄｒ亚型[2 4 ] 的基因序列设计引物。ＰＣＲ扩增产物 ,按ＴＡ克隆方法亚克隆目的片段。3 .重组质粒提取和限制片段长度多态性 (ＲＦＬＰ) :将所有阳性菌落重新划线增殖后 ,提取质粒 ,ＥｃｏＲＩ酶切质粒 ,以观察酶切片段长度多态性。4.Ｄ…     

Viral replication in chronic hepatitis B virus infection

Digestive Diseases and Sciences -     

Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Histological inflammatory activity was strongly related to liver HBcAg expression regardless of HDV superinfection, as confirmed by multivariate analysis. Our results confirm previous studies about the concordance between intrahepatic HBV-DNA replicative pattern and liver HBcAg expression and about inhibition by HDV of high-level HBV replication. However, they suggest that low-level HBV replication may have an important role in causing liver damage also among HDV-infected patients, in a population where the spreading of HBV and HDV is a naturally occurring event.     

Treatment of the chronic hepatitis B virus carrier state

Chronic hepatitis B is no longer untreatable. With the advent of powerful antiviral agents such as adenine arabinoside, and, more importantly, with recombinant DNA technology and advanced culture systems able to produce large quantities of interferons, the prospects for treating patients with chronic hepatitis B virus (HBV) infection have changed completely. In the U.K., carriers not infected at birth are currently being treated with an approximately 50% chance of permanently inhibiting viral replication. In some of these, viral markers appear to be completely eliminated.     

The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B

Background  Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver. Purpose  To review the studies published to date regarding the association of HBV genotypes and subgenotypes in the development of adverse sequelae from HBV. Methods  Review of the literature for articles describing studies of HBV genotype/subgenotypes and development of HCC, cirrhosis, and liver-related death. Results  Eight genotypes of HBV (A through H), which differ from each other in viral genome sequence by more than 8%, and multiple subgenotypes, which differ from each other by 4–8% have been identified. Recently, studies investigating the association between the risks of developing HCC and cirrhosis by specific HBV genotypes and subgenotypes have reported marked differences in outcome. Certain HBV genotypes and subgenotypes, including genotype C, B2-5, and F1, appear to be associated with a higher risk of developing HCC, and others, including genotypes B1, B6, and A2, appear to be associated with a lower risk of complications of HBV. Our understanding of the role of HBV genotypes and subgenotypes on the outcome of HBV infection is limited, as few population-based prospective studies have been performed and most studies compare only the outcome in areas where two genotypes predominate whereas others have not examined subgenotypes. Conclusions  Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.     

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。     

乙型肝炎病毒YMDD变异对临床病情的影响

目的　研究拉米夫定治疗乙型肝炎出现YMDD变异后对临床病情及病毒量的影响 ,以及YMDD变异与前C区变异的相关性。方法　对 13 5例曾用过拉米夫定治疗后复发的住院病例 ,按检查结果分为两组 ,YMDD变异组 61例 ,未变异组 74例 ,对两组病情诊断、病毒载量、肝功能指标 ,YMDD变异与HBeAg、前C区变异的关系进行对照分析。结果　YMDD变异与未变异在慢性肝炎 (轻度 )分别为 9.8% ( 6/ 61)与 8.1% ( 6/ 74)、慢性肝炎 (中度 )分别为 44 .3 % ( 2 7/ 61)与 48.6% ( 3 6/ 74)、慢性肝炎 (重度 )分别为 2 6.2 % ( 16/ 61)与 2 9.7% ( 2 2 / 74)、慢性重型肝炎分别为 9.8% ( 6/ 61)与 14 .9%( 11/ 74)、肝硬化分别为 4.9% ( 3 / 61)与 10 .8% ( 8/ 74) ,各组比较均无显著性差异 (P >0 .0 5 )。两组病毒载量 <1×10 4copies/ml者分别为 1.6% ( 1/ 16)与 2 0 .3 % ( 15 / 74,P <0 .0 1)、1× 10 4～ 10 6copies/ml者分别为 9.8% ( 6/ 61)与 2 9.7% ( 2 2 /74,P <0 .0 1)、≥ 1× 10 7copies/ml者分别为 88.5 % ( 5 4/ 61)与 5 0 .0 % ( 3 7/ 74,P <0 .0 1)。肝功能 6项指标中ALT、ALB、A/G、TBIL对比无显著性差异 (P >0 .0 5 ) ,AST、PTA对比差异显著 (P <0 .0 5 )。YMDD变异组中HBeAg阳性率 68.9% ( 4 2 / 61) ,未变异     

The effect of indomethacin on hepatitis B virus replication in chronic healthy carriers

BACKGROUND: A chronic HBsAg carrier state, a major cause of viral spread in a community, is one of the consequences of hepatitis B virus (HBV) infection. Although successful immunization programs have been initiated to eliminate the virus, there is still a large number of people with HBV infection worldwide. This study was designed to investigate the effect of indomethacin treatment on HBV markers in humans, in comparison with a control group. METHODS: In total, 65 chronic 'healthy' HBV carriers were involved in the study. Patients were divided randomly into two groups. Group I (n = 42) received oral indomethacin 75 mg daily for 6 months. Group II (n = 23) acted as control. Patients in both groups were followed up for 6 months, during which laboratory tests, including viral parameters, were performed periodically. Liver biopsy was done in 17 patients (11/42 of the indomethacin group and 6/23 of the control group). RESULTS: All liver biopsies showed grade 0-2 and stage 0-1 HBV in both groups (P > 0.05). HBsAg positivity did not change in any patient in either group. Five patients who had positive HBeAg in group I became negative 4 months later, while patients in group II continued to be positive at 6 months (P < 0.001). Similarly, all patients receiving indomethacin exhibited a total anti-HBeAg immunoglobulin response at 6 months, while the control group remained the same during this period (P < 0.05). HBV DNA, as detected by polymerase chain reaction in 20/22 (91%), was negative in group I at the end of 6 months. No change was observed in group II (P = 0.007). CONCLUSIONS: Although no biochemical analyses were performed on prostaglandins in the present study, the results suggest that the prostaglandin pathway may be involved in the pathogenesis of the immune response against HBV, and that the suppression of viral replication is achieved as indicated by the disappearance of HBeAg and HBV DNA in healthy chronic HBV carriers.     

Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D

Hepatitis D virus and hepatitis B virus nucleic acids were detected by Northern and Southern blot hybridization in the sera and livers of 85 chronic carriers of HBsAg and anti-hepatitis D followed up for a mean of 10 yr. We identified three subsets of patients: 13 with hepatitis D virus and hepatitis B virus viremia, 53 with serum hepatitis D virus RNA, but without hepatitis B virus DNA and 19 negative for both nucleic acids. Genomic and subgenomic forms of hepatitis D virus RNA were detected only in patients with hepatitis D virus and hepatitis B virus viremia. Histological findings and disease activity at admission were comparable in the three groups of patients, but the outcome was significantly worse in patients with active replication of both viruses; two of them died of terminal liver failure and hepatocellular carcinoma developed in two; the remaining patients had an uneventful course. These results suggest that active hepatitis B virus replication represents an important previously unrecognized determinant of severe liver damage in patients with chronic hepatitis D virus infection. Since hepatitis B virus provides the means for hepatitis D virus secretion and release from infected cells, active hepatitis B virus multiplication favoring the spread of hepatitis D virus from cell to cell may increase the pathogenetic potential of the defective agent.     

Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers

Delta antigen is currently thought to reflect superinfection of the liver with a defective RNA virus (delta agent), requiring helper function from hepatitis B virus for its replication. To assess the influence of delta agent on hepatitis B virus replication in patients persistently infected with both viruses and showing chronic liver disease, we measured serum and liver hepatitis B virus DNA in HBsAg-positive chronic liver disease patients who were either positive or negative for delta antigen in the liver. Hepatitis B virus DNA was assayed in the serum of 21 patients with delta antigen-positive/HBsAg-positive chronic liver disease and in 21 patients with delta antigen-negative/HBsAg-positive chronic liver disease matched for HBeAg/anti-HBe status and underlying liver histology. HBcAg and delta antigen in liver was determined by immunofluorescence or immunoperoxidase staining. In delta antigen-positive/HBsAg-positive chronic liver disease, serum hepatitis B virus DNA was detected transiently in 4 of 21 cases (19%) and was present in these patients at low levels (trace to 2+). In contrast, 9 of 21 (43%) delta antigen-negative/HBsAg-positive chronic liver disease patients were serum hepatitis B virus DNA positive, and five of these had high serum hepatitis B virus DNA levels (3+ to 4+). Serum HBsAg and anti-HBc titers were significantly lower in delta antigen-positive cases and correlated with reduced amount of HBcAg in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)