散发性急性戊型肝炎血清抗体动态变化和肝脏超微结构的病理观察

为探讨散发性戊型肝炎血清抗体动态变化，应用酶联免疫法（ＥＩＡ）检测了７例急性戊型肝炎患者抗戊型肝炎病毒（ＨＥＶ）ＩｇＧ和ＩｇＭ抗体，并对１例患者进行了肝超微结构病理检测。结果表明，发病后１０天至４５天内抗ＨＥＶ－ＩｇＧ和ＩｇＭ滴度最高，发病第４０天仍有肝细胞肿胀，胞浆空化和线粒体固缩等病理变化。患者血清抗－ＨＥＶＩｇＭ滴度在４５天后逐渐下降，２个月内全部消失，抗－ＨＥＶＩｇＧ消长情况与ＩｇＭ相似，但在７个月时仍有３例（４３％）抗体阳性。     

戊型肝炎患者血清IgG抗—HEV动态变化

应用酶联免疫吸附试验(ELISA)检测80例散发性戊型肝炎病人的系列血清表明,IgG抗-HEV于发病后第3天即可阳转,于发病后3～14天和15～30天,IgG抗-HEV累积阳转率分别为68.75％和93.75％。多数病人IgG抗-HEV持续时间较短,发病后4～6个月和1～2年分别有62.50％和95％的病人阴转。90％的病人IgG抗-HEV水平于30天内达到高峰,多数病人IgG抗-HEV水平在急性期较高,恢复期降至低水平。     

戊型肝炎病人和实验感染戊型肝炎病毒的猕猴血清抗——H…

应用人工合成的戊型肝炎病毒（ＨＥＶ）基因组开放读码框架２（ＯＲＦ２）和３（ＯＲＦ３）两段多肽，分别建立了酶联免疫试验（ＥＩＡ），检测８５份实验感染ＨＥＶ的猕猴和１４３份戊型肝炎（简称戊肝）病人血清，结果两组抗－ＨＥＶ ＯＲＦ２阳性率分别为７０．８９％和６８．５３％，均显著高于抗－ＨＥＶ ＯＲＦ３，且前者阳转时间较早，持续阳性时间也较长。虽然多数（９７．３％）抗－ＨＥＶ ＯＲＦ３阳性血清，抗－ＨＥＶ     

散发性急性肝炎抗甲型和戊型肝炎病毒IgM抗体的检测与分析

目的 了解北京地区散发性急性甲型和戊型肝炎的年龄分布、肝功能损伤和预后。方法 用酶免疫法（EIA）检测1995年1月至2000年6月北京地区散发性急性肝炎患者抗甲型肝炎病毒IgM(HAV-IgM)和抗戊型肝炎病毒IgM(HEV-IgM）。结果 在203例散发性急性肝炎患者中,有112例为甲和戊型肝炎病毒感染,合计阳性率占55.2％,其中甲型肝炎占22.2%,戊型肝炎占33％。甲、成语地炎患者均有不同程度肝脏损伤,约75％的患者有中至重度的肝功能损伤（ALT值＞500－≥3500U／ml）,比较重症甲型和戊型肝炎患者肝功能损伤程度（ALT值≥1000－≥3500U/ml）。甲型肝炎患者高于戊型肝炎。追踪患者系列血清及观察临床症状,患者均在2－3个月恢复,ALT转为正常,黄疸消退,未发现甲型和戊型肝炎慢性化病例。结论 散发性急笥肝炎患者一半以上是由肠道传染的甲型和戊型肝炎病毒感染引起,甲型肝炎发病年龄主要以青年居多,戊型肝炎发病主要以青壮年为主,大多数甲肝炎病毒感染引起,甲型肝炎发病年龄主要以青年居多,戊型肝炎发病主要以青壮年为主。大多数甲型和戊型肝炎患者有中至重度的肝功能损伤。在我国病毒性肝炎的防治策略上,对散发性的甲、戊型肝炎的预防应引起同样高度重视。     

戊型肝炎病毒IgM抗体的检测及临床意义

采用合成多肽抗原建立了检测戊型肝炎病毒－ＩｇＭ的酶联免疫吸附试验方法，成本低，操作简便，快速，重复性好，特异性强。与抗甲型肝炎病毒，乙型肝炎病毒，丙型肝炎病毒的ＩｇＭ抗体无交叉反应，排除了ＲＦ的干扰，且可被β－巯基乙醇抑制而不起反应。     

一起戊型肝炎暴发的血清抗体比较研究

目的评价戊型肝炎(戊肝)抗体E2-IgM(抗-HEV E2-IgM)酶联免疫试剂(捕获法)在反映戊肝流行特征和对戊肝早期诊断中的作用.方法在首发病例26 d后对某单位戊肝暴发人群和相邻单位对照人群进行血清抗-HEV E2-IgM、IgG检测;部分人群进行美国Genelabs抗-HEV IgM、IgG的平行检测.结果抗-HEV E2-IgM试剂捕获法在对照人群中仅检出1例阳性(0.11%),且阳性和阴性之间可明显区分,其特异度为99.89%;在暴发流行人群中检出145例阳性(8.66%),显著高于对照人群(P＜0.001);暴发人群中戊肝患者的血清学动态变化为抗-HEV E2-IgM在暴露时间为30～60d时保持较高吸光度(A值),随着时间的延长A值呈明显下降趋势;抗-HEV E2-IgM阳性在该组人群中与性别和年龄无关;在暴发人群抗-HEV E2-IgM(+)的115例患者中,Genelabs抗-HEV IgG检测出88份阳性,检出率为76.52%,漏检27例,漏检率为23.48%.对照人群随机抽样179例患者中有20例Genelabs抗-HEVI IgG(+),阳性率为11.17%.在110份抗-HEV E2-IgM(+)的血样中,Genelabs抗-HEVIgM只检测出76份,检出率为69.09%;有16例患者Genelabs抗-HEV IgG、IgM均未能检出;Genelabs抗-HEV IgG和IgM的不一致率为25.45%.结论抗-HEV E2-IgM具有99%左右的特异度,与在正常人群中检出较高阳性率的Genelabs抗-HEV IgG试剂相比,减少了假阳性;抗-HEV E2-IgM与Genelabs抗-HEV IgM、IgG相比,对急性戊肝感染诊断的灵敏度提高了25%～30%,减少了漏诊;抗-HEV E2-IgM试剂盒操作简单、快速,本底较好,不存在酶结合物不足的问题.     

一起戊型肝炎暴发的血清流行病学调查

目的 了解一起戊型肝炎暴发的血清学特点。方法 对某单位在10d内先后发病的5例急性黄疸性肝炎患者、在该单位食堂就餐的1675人(暴发人群)及未就餐的邻近单位883人(对照人群)的血清在首发病例26d后进行抗-HEV IgM和IgG检测，数据进行统计学分析。结果 5例患者抗-HEV IgM和IgG均为阳性。暴发人群抗-HEV IgM和IgG的阳性率分别为8．7％和38．4％，而对照人群仅分别为0．1％和28．6％，差别均有非常显著意义。暴发人群145例抗-HEV IgM( )中，ALT增高32例，明显高于IgM(-)及对照；而抗-HEV IgM(-)的ALT增高比例并不高于对照人群。4例患者系列血清检测见抗-HEV IgM逐渐下降，感染后4个月多数转阴，而IgG在感染后第2～3个月达高峰，随后缓慢下降。暴发人群中抗-HEV IgM( )的IgG平均水平最高，IgM(-)而IgG( )的IgG平均水平亦明显高于对照，提示暴发人群中既往感染者受到了免疫加强。暴发人群中抗-HEV IgM( )者在性别及年龄组间差异无显著意义，但其中ALT增高男性的比例显著高于女性，而与年龄无关。结论 本次急性黄疸性肝炎的暴发由戊型肝炎病毒引起，与食源有关；抗-HEV IgM和IgG不仅可用于临床病例诊断，也可用于人群调查；感染危险性与年龄及性别无关，但男性ALT增高更常见。     

戊型肝炎患者血清戊型肝炎病毒RNA的动态观察及意义

目前 ,国内外对戊型肝炎 (ＨＥ)患者病毒血症已有研究 ,各家报道有明显不同 ,我们采用逆转录 聚合酶链反应方法检测 32例ＨＥ患者系列血清 ,探明ＨＥ患者病毒血症持续时间和消长规律。检测对象为中国医大二院传染科1995年 1月至 1996年 10月期间住院患者 32例 ,临床诊断为戊型肝炎。分别收集患者病后 0～ 7ｄ、8～ 14ｄ、15～ 12ｄ、2 2～ 2 8ｄ系列血清共 12 5份 ,用异硫氰酸胍一步法抽提ＨＥＶＲＮＡ。引入一对外引物序列为 :外正向引物 (4 45 9 44 78) 5′ ＧＣＡＴＴＡＴＧＧＡＧＧＡＧＴＧＴＧＧ 3′,外反向引物 (4 877 485 8) 5′ Ｃ…     

散发性戊型肝炎病毒感染的诊断

用基因工程重组的戊型肝炎病毒基因结构区第二码框架和第二读码框架具有免疫表位的嵌合抗原，建立了间接酶联免疫法，检测散发性急性肝炎病人血清中抗－ＨＥＶＩｇＧ和ＩｇＭ抗体。在４６例急性肝炎病人中出抗－ＨＥＶＩｇＧ抗体阳性７例，阳性率为１５．２２％，７例ＩｇＧ抗体阳性中，有５例ＩｇＭ抗体也阳性，占７１．４％。     

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.     

我国急性散发性戊型肝炎病毒部分核苷酸序列分析

用逆转录套式聚合酶链反应（ＲＴ－ｎＰＣＲ）自深圳、长春、杭州等地４１份急性散发性戊型肝炎病人血清中获得２８株ＨＥＶｃＤＮＡ，对其中３株ＨＥＶｃＤＮＡ的ＯＲＦ２基因片段，用荧光法直接测定其核苷酸序列，并与戊型肝炎病毒墨西哥株（Ｍ）、缅甸株（Ｂ）和新疆流行株（ＣＨ１·１）进行了比较，结果该３株散发性ＨＥＶ与Ｍ株的核苷酸序列同源性分别为８０．２％、７９．９％和７９．４％；与Ｂ流行株的同源性为９５．５％、９３．９％和９５．１％；与散发株的同源性为９３．４％、９２．３％和９３．８％；与ＣＨ１·１的同源性为９７．０％、９６．５％和９５．９；表明该３株散发性ＨＥＶ与ＨＥＶ（Ｂ）和ＣＨ１·１的核酸序列同源性较高，可能属同一亚型。     

Presence of viral replicative intermediates in the liver and serum of patients infected with hepatitis C virus

Hemophilic patients may present immunological dysfunctions resulting from either human immunodeficiency virus (HIV) infection, or other factors like impure factor VIII concentrate and other viral infections. We evaluated prospectively the serologic response to polio vaccination of Israeli hemophilic patients who were vaccinated during an outbreak of poliomyelitis. Eighty-two hemophilic patients, 43 seronegative and 39 seropositive for human immunodeficiency virus (HIV), were vaccinated with enhanced inactivated poliovirus (elPV). Titers of antibodies for poliovirus types 1–3 were determined before and 4 weeks after immunization. T helper and suppressor lymphocytes (T4 and T8), B and T lymphocyte mitogenic response, and natural killer cells were tested and correlated with the response to vaccination. Both groups responded to vaccination with increased titers of antibodies to the three viral types, 4 weeks after immunization. HIV-seronegative patients, however, exhibited higher titers than the HIV-seropositive group. The same pattern was found when 21 patients were tested 1 year after the exposure to elPV. HIV seropositive patients were grouped according to their T4 count (between 16/μ and 500/μ). There was no statistically significant difference in the response of these different groups to vaccination. No correlation was found between the response to vaccination and other immune parameters. These results suggest that asymptomatic HIV-seropositive hemophilic patients respond well to elPV, irrespective of their T4 count. © 1993 Wiley-Liss, Inc.     

Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.

A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen.     

Gene expression profiles of T cells from hepatitis E virus infected patients in acute and resolving phase

Background and Aims  

Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury.     

Autoimmune liver disease-associated serologic profiling in Chinese patients with acute hepatitis E virus infection

The association between hepatitis E virus (HEV) and autoimmune liver diseases has been well-researched; however, the focus has been on autoimmune hepatitis (AIH) and not primary biliary cholangitis (PBC). Therefore, we aimed to investigate the prevalence and evolution of AIH- and PBC-related autoantibodies in Chinese patients with HEV infection. In this retrospective study, 164 patients with acute HEV were included, specifically those whose liver autoantibody results were available and who had no pre-existing liver disease at the time of HEV diagnosis. Positive liver autoimmune serology was present in 69 (42.1%) patients and 21 (12.8%) had at least two autoantibodies at diagnosis. Greater age and alkaline phosphatase levels were independent risk factors for autoantibody positivity. Follow-up serologic tests, which were available for 27 of the 69 autoantibody-positive patients, showed that although antinuclear antibodies disappeared in 11/20 (55.0%) and antimitochondrial antibodies disappeared in 4/5 (80%) patients, 16 still remained positive for autoantibodies and two of them even developed new PBC-related antibodies, as described below. One patient developed a rim-like ANA pattern, accompanied by an enhancement of anti-gp210 positivity; and the other was diagnosed as PBC, based on chronic elevation of cholestatic enzymes and presentation with de novo AMA-M2, 18 months after HEV clearance. In conclusion, AIH- and PBC-related autoantibodies are frequently present during acute HEV infection, indicating that HEV should be excluded before diagnosing AIH and/or PBC. Importantly, some cases maintained or developed autoantibodies after viral clearance, and one patient subsequently developed PBC, highlighting that these individuals warrant long-term follow-up.