成年树Qu实验感染丁型肝炎病毒的初步研究

在证实成年树Ｑｕ可感染人乙型肝炎病毒的基础上，进行了丁型肝炎病毒－乙型肝炎病毒实验感染的探索。ＨＤＶ／ＨＢＶ阳性人血清经同时和重叠感染方式接种于成年树Ｑｕ后，定期留取感染树Ｑｕ血清及肝组织，检测血清中ＨＢｓＡｇ、ＨＤＡｇ、抗－ＤＥ、ＨＢＶＤＮＡ及ＨＤＶＲＮＡ，初步探讨成年树Ｑｕ实验感染ＨＤＶ的可能性。     

乙型慢性肝炎重叠感染丙型和丁型肝炎病毒的临床分析

乙型慢性肝炎重叠感染丙型和丁型肝炎病毒的临床分析姚桢，刘茂才，王朝栋报道２６７例乙型慢性肝炎（含慢迁肝１８７例，慢活肝８０例）的丙型肝炎病毒（ＨＣＶ）和丁型肝炎病毒（ＨＤＶ）重叠感染情况并作临床简要分析。调查患者血清ＨＢｓＡｇ、抗－ＨＢｓ、ＨＢｅＡｇ...     

检测丁型肝炎病毒RNA打点杂交法的建立及其应用

经缺口平移法以ａ－３２Ｐ－ｄＣＴＰ标记１．０ｋｂ的丁型肝炎病毒（ＨＤＶ）ｃＤＮＡ片段为探针，采用蛋白酶Ｋ直接从血清中提取ＨＤＶＲＮＡ，建立了检测血清中ＨＤＶＲＮＡ的打点杂交法，其灵敏性可达１ｐｇ水平，与乙型肝炎病毒（ＨＢＶ）ＤＮＡ无交叉杂交反应；并应用于检测我国５９４９份ＨＢｓＡｇ阳性血清中的ＨＤＶＲＮＡ，共检出１７６份ＨＤＶＲＮＡ阳性，检出率为２．９５％。     

我国九个地区丁型肝炎病毒感染状况及其与乙型肝炎病毒复制指标关系的研究

对１５４５例各类乙型肝炎病毒表面抗原（ＨＢｓＡｇ）阳性肝病和无症状ＨＢｓＡｇ携带者的血清进行了乙型肝炎病毒（ＨＢＶ）与丁型肝炎病毒（ＨＤＶ）感染标记物的测定。结果表明，ＨＤＶ感染率为１３．０１％，其中ＨＤＡｇ和抗－ＨＤ阳性率分别为２．９１％和１０．０９％。而且在全国九个地区均有ＨＤＶ感染者存在，说明其分布是较为广泛的。同时还表现出，男性高于女性，慢性肝炎、重型肝炎及原发性肝癌高于急性肝炎和无症状ＨＢｓＡｇ携带者。提示ＨＢＶ与ＨＤＶ合并感染或重叠感染可能导致病情加重和感染的慢性化。本项研究结果还揭示，在ＨＢＶ与ＨＤＶ合并或重叠感染时，可能对ＨＢＶ的复制指标（ＨＢｅＡｇ·ＨＢＶＤＮＡ）有一定的抑制现象。     

中国丁型肝炎病毒抗原编码区基因异质性与乙型肝炎 …

为了研究乙型肝炎病毒（ＨＢＶ）与丁型肝炎病毒（ＨＤＶ）的协同作用，阐明在我国不同地区与民族中ＨＤＶ感染率与ＨＢＶ亚型的关系，我们经筛选获得西藏、内蒙、河南、四川等地藏、蒙、汉族共８份血清，ＨＢｓＡｇ和ＨＤＶ ＲＮＡ皆为阳性。ＨＢｓＡｇ亚型经反相间接血凝法测定，经逆转录－聚合酶链反应获得ＨＤＶ的ｃＤＮＡ片段，将其克隆到载体ｐＧＥＭ－３ｚｆ（－）或ｐＧＥＭ－Ｔ上，进行序列分析，确定其基因亚型。经比较研     

我国九个地区丁型肝炎病毒感染状况及其与乙型肝炎…

对１５４５例各类乙型肝炎病毒表面抗原（ＨＢｓＡｇ）阳性肝病和无症状ＨｓＡｇ携带者的血清进行了乙型肘炎病毒（ＨＢＶ）与丁型肝炎病毒（ＨＤＶ）感染标记物的测定。结果表明，ＨＤＶ感染率为１３．０１％，其中ＨＤＡｇ和抗－ＨＤ阳性率分别为２．９１％和１０．０９％。而且在全国九个地区均有ＨＤＶ感染者存在，说明其分布是较为广泛的。同时还表现出，男性高于女性，慢性肝炎、重型肝炎及原发性肝癌高于急性肝炎和无症状ＨＢ     

反义寡脱氧核苷酸在鸭体内抑制鸭乙型肝炎病毒复制与 …

目的 研究反义核酸的抗病毒作用。方法 设计合成了针对鸭乙型肝炎病毒（ＤＨＢＶ）前Ｓ（ＰｒｅＳ）基因区第９５１－９６８位核苷酸的硫代反义寡脱氧核苷酸（ＡＳ－ＯＤＮ），以２０μｇ／ｇ体重／日剂量对３只腹腔感染ＤＨＢＶ５．２毒株后，血清ＤＨＢｓＡｇ及ＤＨＢＶ ＤＮＡ阳性鸭连续静脉注射１０天，同时以等体积生理盐水注射另３只感染鸭作为对照。结果 对照鸭注射生理盐水后，血清ＤＨＢｓＡｇ及ＤＨＢＶ ＤＮＡ阳性未     

乙肝张黄曲霉毒素B1诱发树Qu肝癌的病理变化

目的：对人乙型肝炎病毒（ＨＢＶ）和黄曲霉毒素Ｂ１（ＡＦＢ１）引起的树Ｑｕ肝脏病变进行动态比较观察。方法：成年树Ｑｕ按不同处理分为Ａ（ＨＢＶ＋ＡＦＢ１）、Ｂ（ＨＢＶ）、Ｃ（ＡＦＢ１）、Ｄ（空白对照）４组。全部动物定期肝活检,并于１６０周结束实验时处理所有存活者。各次活检及尸检肝组织均作常规病理组织学检查,部分同时作ＨＢｓＡｇ及ＨＢｓＡｇ免疫组织化学、ＨＢＶＤＮＡ原位杂交,以及ＰＡＳＤ、网状纤维染色等     

新生儿乙型肝炎疫苗免疫失败同孕妇血清乙型肝炎…

以ＨＢｓＡｇ，ＨＢｅＡｇ阳性孕妇作为研究对象，用病例－对照研究方法，比较婴儿乙型肝炎疫苗免疫失败和婴儿疫苗免疫成功两组孕妇分娩时血清乙型肝炎病毒ＨＢＶ－ＤＮＡ含量进一步用定群方法研究母亲ＨＢＶ－ＤＮＡ含量与其婴儿免疫后ＨＢｓＡｇ持续携带 关系，证实孕妇血清ＨＢＶ－ＤＮＡ高含量是婴儿免疫失败的主要原因。     

丁型肝炎病人肝组织HDVRNA与 HBVDNA的表达及关系

目的 探讨丁型肝炎病人肝组织中ＨＤＡｇ、ＨＤＶＲＮＡ与ＨＢＶＤＮＡＧ表达及关系。方法 应用免疫组化和原位杂交技术检测了７９全丁型肝炎病人肝组织ＨＤＡｇ、ＨＤＶＲＡＮ～ＨＢＶＤＮＡ表达,以５２例型肝炎病人肝组织作对照。结果 丁型肝炎ＨＢＶＤＮＡ检出率（２７％）低于乙型肝炎（４４％）（Ｐ〈０．０５）。在坏死灶边缘肝细胞和气球样变肝细胞浆内有大量的ＨＤＶＲＮＡ蓄积或ＨＤＡｇ呈强型强表达,ＨＤＶＲＮＡ表达     

重型病毒性肝炎中丁型肝炎病毒的检测

为了探讨丁型肝炎病毒（ＨＤＶ）感染在重型病毒性肝炎中的作用，对北京佑安医院１９８０年至１９８９年收治的５４例急性和亚急性重型肝炎和３８例急性乙肝患者血清，应用国产ＨＤＶＥＬＩＳＡ试剂测定抗－ＨＤ、抗－ＨＤＩｇＭ和ＨＤＡｇ，应用斑点杂交技术测定ＨＤＶＲＮＡ。结果发现重型肝炎组ＨＯＶ－Ｍ检出率明显高于急性乙肝组（２７．８％比５．３％．Ｐ＜０．０５）。单独ＨＢＶ感染和ＨＤＶ／ＨＢＶ混合感染的重型肝炎患者均有较高的病死率。提示ＨＤＶ感染是重型肝炎中重要的病原学因素之一，ＨＤＶ与ＨＢＶ具有协同作用加重肝损害，导致肝衰竭。     

Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.     

Persistent delta antigenaemia in chronic delta hepatitis and its relation with human immunodeficiency virus infection.

The prevalence of persistent hepatitis delta (HD) antigenaemia and associated factors in patients with chronic infection with the hepatitis delta virus (HDV) were investigated. Among 157 consecutive patients known to be carriers of hepatitis B surface antigen (HBsAg), 36 (23%) had one serum marker of HDV infection (anti-HD and/or HDAg). Nine of the patients with an HDV marker were HDAg positive, including three who were anti-HD negative. A follow-up over a mean period of 13 months showed that five of five patients had a persistent HD antigenaemia. This serological profile was associated with the presence of antibody to the human immunodeficiency virus (anti-HIV) (P < 0.01), serum HIV antigen (HIVAg) (P < 0.2), and the female sex (P < 0.05). Persistent HD antigenaemia could be the consequence of the suppression of T cell cytotoxic activity against hepatocytes expressing HDAg, a lower humoral response, and/or hormonal factors.     

The serology of delta hepatitis and the detection of IgM anti-HD by EIA using serum derived delta antigen

A sensitive and specific capture assay for IgM antibody to hepatitis D virus (HDV) was developed employing serum-derived delta antigen (HDAg). In a retrospective and prospective study of an outbreak of hepatitis B (HB), 135 hepatitis B surface antigen (HBsAg) positive drug-abusers with acute hepatitis and 18 HBsAg carriers, attending various hospitals and clinics in Dublin, were found to be infected with HDV. Serological follow-up was available from 24 of those with acute hepatitis allowing a comparison of the duration and level of IgM anti-HD with the more commonly used markers, HDAg and anti-delta (anti-HD), and an assessment of the usefulness of each. HDV and HB serology was grossly altered by human immunodeficiency virus (HIV) in two patients, with severe clinical manifestation in one. All 135 patients with HDV co-infection had delta antigenaemia. In co-infections with optimum sampling times, the mean duration of delta antigenaemia was 21 days. IgM anti-HD was always found between HDAg and sero-conversion to anti-delta and was the only 'window' marker present in five cases. The mean duration of IgM anti-HD was four weeks (optimum at 2.8 weeks) and was of moderate or low titre and occurred simultaneously with HDAg in 78%. In HDV-infected HBsAg carriers, high-titre IgM anti-HD (greater than 1/10,000) persisted for the duration of the study and is a useful indicator of chronic HDV infection. IgM anti-HD was not found in 202 random blood donors nor in 205 patients with non-B hepatitis or other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-S1 and Pre-S2 gene-encoded proteins in liver and serum in chronic hepatitis delta infection

Frozen cryostat sections and sera from 30 patients with chronic delta infection were examined for pre-S1 and pre-S2 gene-encoded proteins, and the results were compared to markers in liver and serum HBV and HDV replication. Pre-S1 and pre-S2 were detected by indirect immunofluorescence (IF) in the liver in all 26 patients with histochemically demonstrable HBsAg. Pre-S peptides were found by double IF to have a predominantly cytoplasmic expression and to be located in the same hepatocytes expressing HBsAg. Liver cells expressing hepatitis delta antigen (HDAg) were frequently negative or very weakly positive for HBsAg and pre-S peptides, but occasional HDAg positive hepatocytes were also strongly positive for HBsAg and for pre-S peptides, particularly pre-S2. Circulating pre-S1 was detected in 24 patients (80%) and pre-S2 in 27 (90%). Detection of pre-S peptides in liver and serum was independent of HBV and HDV replication and of the HBV-DNA integration state. There was no correlation between the amount of circulating pre-S peptides and serum HBV-DNA and HDV-RNA. These results indicate that in chronic HDV infection, formation and secretion of pre-S peptides and of HBsAg occur independently of HBV and HDV replication and secretion. They further indicate that in the acquisition by replicating HDV of an HBV-derived envelope in the liver, both HBsAg and pre-S peptides are concomitantly available but circulating HDV-RNA is not invariably associated with the presence of these peptides in serum.     

Hepatitis B and D virus infection among drug abusers in Taiwan

Approximately 15 to 20% of the general population in Taiwan are chronic hepatitis B surface antigen (HBsAg) carriers. However, the incidence of hepatitis D virus (HDV) infection is low (5-8%) in patients with HBsAg-positive chronic liver diseases in this area. To evaluate the prevalence of hepatitis B virus (HBV) and HDV infection among drug abusers in Taiwan, serum samples were collected from 152 drug abusers at the Taipei Municipal Anti-Narcotic Institute and test for HBV and HDV markers. Of these, 24 (15.8%) were HBsAg positive, and only 15 (9.9%) were seronegative for all HBV markers. Of the 115 intravenous drug abusers, serum antibody to hepatitis D antigen (anti-HD) was positive in 78.9% of 19 persons who were HBsAg positive, and in 7.5% of 80 persons who were positive for antibody to HBsAg (anti-HBs). Anti-HD was not detected in the sera from all 37 nonintravenous drug abusers regardless of the status of their HBV markers. Also, none of 63 asymptomatic HBsAg carrier pregnant women or 23 patients with acute type B viral hepatitis had measurable anti-HD in their sera. Thus, the high frequency of HDV detected among Chinese HBsAg carrier intravenous drug abusers in Taiwan is similar to that reported in Western countries.     

Diagnostic significance of IgM antibody to hepatitis delta virus in fulminant hepatitis B

The prevalence of hepatitis delta virus (HDV) infection was studied in 25 adult patients with fulminant hepatitis who were admitted consecutively to our unit from February, 1986, to September, 1988. Enzyme and radioimmunoassays were used for the detection of serological markers of HAV, HBV, and HDV (HDAg, IgM anti-HD, total [IgG] anti-HD) infections. Two hundred twenty-nine serum samples (three to 19 samples/patient) were tested for serological markers of HDV infection. Of the 25 patients, 17 (68%) were HBsAg-positive, and the remaining eight (32%) were HBsAg-negative on admission to the hospital. All patients were seropositive for IgM anti-HBc. Serological markers of HDV infection were detected in 13 (52%) of the 25 patients. In particular, HDV infection was observed in nine (53%) of the 17 HBsAg-positive and in four (50%) of the eight HBsAg-negative patients with type B fulminant hepatitis. Survival was 16.7% for patients with hepatitis B and 57.8% for patients with B and D coinfection. Coinfections were responsible for fulminant hepatitis in 100% of drug addicts and 40% in patients who were not drug addicts. All patients with HBV/HDV coinfections became seropositive for IgM anti-HD. The results show that HDV infection has a significant role (52%) in type B fulminant hepatitis in an area with a moderate prevalence of HBV infections, that it should be tested in cases with early clearance of HBsAg, and that it does not seem to be accompanied by a high fatality rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

血清抗—HD—IgM方法的建立及初步应用

本文采用国产试剂建立抗-HD-IgM的EIA检测方法,开采用不同血清稀释度进行研究。结果表明最适宜血清稀释度为10~(-2),按10~(-2)作血清稀释,对45份HDV/HBV感染的患者血清进行抗-HD-IgM检测,阳性23例(51.11％),17份单纯HBV感染者及9份正常人标本均为阴性,表明本方法具有较好的特异性和敏感性。45例HDV/HBV感染者中,血清HDAg(+)32例(71.11％),抗-HD(+)18例(40％)。     

Immune response to synthetic peptides of hepatitis delta antigen.

Hepatitis delta antigen (HDAg) is the only viral protein known to be expressed during hepatitis delta virus (HDV) infection. Detection of antibody to HDAg (anti-HD) is the usual method for diagnosis of HDV infection since viremia lasts only a few weeks. In an effort to identify the major epitopes recognized by humans during natural infection, four oligopeptides including residues 2 to 17 (SP1), 155 to 172 (SP2), 168 to 182 (SP3), and 189 to 211 (SP4) of the HDAg molecule were synthesized and probed by enzyme-linked immunosorbent assay with a panel of 80 serum specimens from 45 patients suffering from either HDV-hepatitis B virus coinfections (n = 17) or HDV superinfections (n = 28). Sera from infected patients recognized these relatively short peptides. Peptide SP2 was the most antigenic; 71% of serum specimens reacted. Antibody to SP2 was also the commonest in sera taken early in the course of the disease. Peptide SP2 corresponds to one of the two regions which is highly conserved between different isolates. Among the 63 serum specimens which scored anti-HD positive by a commercial assay, all but 3 reacted to at least one of the peptides (95% agreement). Peptide assays appeared to be significantly more sensitive than the commercial assay with native HDAg early in the course of HDV infection since 14 of 17 (82%) serum specimens which scored anti-HD negative in the commercial assay reacted to one or more peptides. All serum specimens giving one or more positive results with the various peptides were confirmed as being HDV positive by an inhibition assay with free peptide in solution. The immune response to HDAg peptides vared greatly between individuals. No specific reactivity profile could be assigned to those with either HDV-hepatitis B virus coinfections or HDV superinfections. Overall, HDAg peptides appeared to be convenient reagents in addition to native antigen for the development of new and improved diagnostic tests for HDV infection.