戊型肝炎病毒核酸阳性血浆经输血传播感染恒河猴的研究

目的了解戊型肝炎病毒(HEV)核酸阳性血浆对灵长类动物的感染性和致病性。方法对抗-HEV IgM阳性而IgG阴性志愿献血员血浆进行HEV RNA检测，并将存在病毒血症献血员的10ml血浆静脉输入健康恒河猴，观察其对恒河猴的感染性和致病性。结果从1份抗-HEV IgM阳性而IgG阴性志愿献血员血浆中分离出HEV基因IV型RNA片段。该份血浆输入恒河猴后，恒河猴出现典型急性肝炎生物化学和病理表现，病毒血症，血清抗-HEV IgM和IgG抗体阳转。结论HEV病毒血癌献血员血浆输入可以引起灵长类动物的HEV感染以及急性肝炎，提示HEV经输血传播的可能性。     

秦皇岛地区孕妇戊型肝炎病毒感染的血清学及临床特征

目的调查秦皇岛地区孕妇人群中戊型肝炎病毒(hepatitis E virus, HEV)感染的血清流行率及临床特征。方法选取2016年1月至2017年12月在河北省秦皇岛市第一医院进行定期产检的864例孕妇作为研究对象,随机抽取同期在本院体检的非孕女性836例作为对照组。采用ELISA方法检测血清中抗-HEV IgM、抗-HEV IgG抗体。所有标本均检测肝功能指标。结果孕妇抗-HEV IgM阳性率为3.82%,高于非孕女性(2.03%),差异有统计学意义(P0.05)。急性HEV感染的孕妇ALT、AST、TBil、DBil检测均值高于急性HEV感染的非孕女性,差异有统计学意义(P0.05)。孕晚期抗-HEV IgM(6.49%)和抗-HEV IgG(22.73%)阳性率明显高于孕早、中期(P0.05)。孕晚期急性HEV感染者其ALT、AST、TBA、TBil、DBil检测均值高于孕早、中期(P0.05),Alb检测均值低于孕早、中期(P0.05)。结论秦皇岛地区孕妇人群存在HEV感染,HEV感染可引起孕妇(尤其孕晚期)较严重的肝损害,应高度重视孕妇戊型肝炎的防控。     

重组抗原检测戊型肝炎病毒IgM抗体及其意义

用戊型肝炎病毒(HEV)重组抗原建立酶联免疫吸附试验(ELISA)，检测肝炎患者和健康供血人群血清中抗戊型肝炎病毒IgM类抗体(抗-HEV IgM)，并评价其检测意义。在与合成肽抗原比较检测的77份急性戊型肝炎患者血清中，有54份(70.1%)由重组抗原捡测抗-HEV IgM阳性。其阳性率明显高于台成酞抗原(21/77,27．3％)。15例戊型肝炎患者双份血清用重组抗原ELISA检铡，急性期血清有11份抗-HEV IgM阳性，恢复期血清仅1份阳性。抗-HEV IgG阳性的健康供血者(8人)和甲、乙、丙型肝炎患者(11例)无1例IgM抗体阳性。结果表明，抗-HEV IgM可以作为戊型肝炎病毒新近感染的标志。HEV重组抗原检铡抗-HEV IgM敏感性高，特异性强，有助于戊型肝炎病毒感染的早期诊断。     

孝感地区孕妇感染戊型肝炎病毒流行病特征和母婴HEV IgG传递率调查

目的调查湖北省孝感地区孕妇戊型肝炎病毒感染状况及流行特征、母婴抗-HEV IgG传递率和抗-HEV IgG在婴幼儿体内的消长。方法孕妇446例和相对应年龄的普通健康女性463例,收集其人口统计学数据并采集其血清标本;采集20例抗-HEV IgG阳性孕妇分娩的新生儿血清,并追踪收集25例抗-HEV IgG阳性婴幼儿血清(每两月采集一次,共采集7次),采用ELlSA法检测血清抗-HEV IgG和抗-HEV IgM,对抗-HEV IgM阳性标本进行HEV基因分型。结果对照人群抗-HEV IgG阳性率19.22%(89/463);抗-HEV IgM阳性率1.08%(5/463)),孕妇抗-HEV IgG阳性率为19.73%(88/446),抗-HEV IgM阳性率1.57%(7/446),两组相比差异无统计学意义(P0.05)。孕妇和对照人群随年龄增长抗-HEV IgG阳性率增高,26-30年龄段孕妇抗-HEV IgG阳性率高于对照人群。农民孕妇抗-HEV IgG阳性率高于其他职业孕妇。母婴抗-HEV IgG传递率为80.00%(16/20)。追踪检测婴幼儿抗-HEV IgG体内存在时间为4~12月。孕妇和对照人群中各有1个HEV RNA阳性标本,HEV基因序列同源性为99.34%,基因型为IV d亚型。结论孝感地区孕妇人群存在HEV散发感染,以无症状的隐性感染为主;抗-HEV IgG母婴传递率较高,但该抗体在婴幼儿体中存在的时间较短。     

急性戊型肝炎血清抗-HEV IgM、IgG和HEV RNA动态变化及其诊断价值

目的 分析急性戊型肝炎(AHE)患者血清抗-HEV IgM、抗HEV-IgG和HEV RNA变化规律。方法 2016年1月～2018年3月北京佑安医院就诊的AHE患者217例,动态检测血清抗-HEV IgM、抗HEV-IgG和HEV RNA变化。结果 首次检测血清抗-HEV IgM、IgG和HEV RNA均阳性31例(14.3%),抗-HEV IgM和IgG阳性99例(45.5%),抗-HEV IgM阳性8例(3.7%),抗-HEV IgG阳性72例(33.2%),抗-HEV IgM和HEV RNA均阳性3例(1.5%),抗-HEV IgG和HEV RNA均阳性2例(0.9%),抗-HEV IgM、IgG、HEV RNA均阴性2例(0.9%);在75例患者二次检测中,显示血清抗-HEV IgG阳性增多;在138例有准确的发病日期患者,在第1、2、3、4病周和第4病周后,血清HEV RNA阳性检出率分别为49.0%(25/51)、10.2%(6/59)、3.1%(1/32)、4.0%(1/25)和0.0%(0/0);血清抗-HEV IgM阳性检出率分别为70.6%(36/51)、69.5%(41/59)、65.6%(21/32)、48%(12/25)和56.5%(13/23);血清抗-HEV IgG阳性检出率分别为90.2%(46/51)、88.1%(52/59)、96.9%(31/32)、100%(25/25)和100.0%(23/23)。结论 AHE患者血清抗-HEV IgM、IgG和HEV RNA存在一定的变化规律,血清抗-HEV IgG阳性,结合典型的急性肝炎过程和排除其他病因后,可以诊断为AHE。     

应用合成肽检测戊型肝炎病毒抗体的实验研究

本文利用多肽合成技术在戊型肝炎病毒(HEV)基因结构区内的开放读码框(ORF)-2和ORF-3区合成了P1、R2二条具有明确抗原表位的多肽,作为EIA法抗-HEV诊断试剂的固相抗原测定抗-HEV。在急性甲型肝炎中抗-HEV的检出率为7.8％,慢性乙型肝炎的检出率为2.9％,志愿献血员1.4％,急性输血性丙型肝炎为0％。抗-HEV诊断试剂检测的CV值为6.8％-9.1％,经162例血清标本的检测与Genelaps抗-HEV诊断试剂的结果对比,其符合率达98.8％。结果表明:本室抗-HEV诊断试剂的灵敏度、特异性检测结果满意,精密度(precision)检测优于部颁标准。     

抗戊型肝炎病毒E2 IgM诊断急性戊型肝炎的敏感性和特异性

目的评价抗戊型肝炎病毒（HEV）衣壳蛋白重组抗原E2 IgM（抗-E2 IgM）诊断急性散发性戊型肝炎的敏感性和特异性。方法用酶联免疫吸附法检测176份急性散发性戊型肝炎和191份急性散发性非甲～非戊型肝炎患者血清中抗-E2 IgM，与国产传统试剂和新加坡Genelabs试剂检测的IgM（GL—IgM）作比较；对抗-E2 IgM阳性血清检测血清中HEV RNA，采用logistic回归分析检测抗-E2 IgM和HEV RNA的相关因素。结果在176份急性戊型肝炎患者血清中，抗-E2 IgM的检出率为68．75％，国产传统试剂抗-HEV IgM检出率为56．25％，x^2IgM=6．49，P〈0．05。在191份急性非甲～非戊型肝炎血清中有37例（19．37％）抗-E2 IgM阳性，其中11例GL—IgM同时阳性；在158份抗-E2 IgM阳性血清中，有81例HEV RNA阳性（51．27％），其中急性戊型肝炎的阳性率为57．02％，急性非甲～非戊型肝炎的阳性率为32．43％，23例抗-E2 IgM阴性的急性戊型肝炎患者的血清，无一例检测到HEV RNA。Logistic多因素回归分析发现，抗-E2 IgM的检出率与发病至人院时间、年龄、血清胆红素、血清氨基转移酶水平无关，血清丙氨酸氨基转移酶水平与HEV RNA水平呈正相关（P=0．024）。结论抗-E2 IgM是HEV急性期感染敏感性和特异性强的血清学指标；HEV感染仍是部分临床诊断为急性非甲～非戊型肝炎的病因；持续HEV病毒血症可能是影响急性戊型肝炎病情的重要因素。     

各型肝炎病毒单纯及重叠感染的研究

目的 探讨病毒性肝炎患者甲～戊，庚型肝炎病毒(HAV-HEV，HGV)单纯感染及重叠感染情况。方法 采用EIA法检测病毒性肝炎患者血清抗-HAV IgM，HBV标志物、抗-HCV IgM、抗-HDV IgM、抗-HEV IgM、抗-HGV IgM。结果 共检测210例病毒性肝炎患者HAV-HEV、HGV血清标志物，20例未检出(9．5％)，190例患者检出标志物阳性(90．5％)。HBV感染率89，5％(188／210，其中有34例为既往感染，占16．2％，现症感染154例，占73．3％)；HAV感染率29．0％(61／210)，HCV、HDV感染率均为8．1％(17／210)、HEV、HGV感染率依次为10．0％(21／210)、7．1％(15／210)。各临床类型中单纯感染占61．4％(129／210)，二重感染占32．4％(68／210)，以HAV HBV、HBV HDV、HBV HEV感染模式最常见，三重感染占6．2％(13／210)，以HAV HBV HDV感染模式最常见；临床上以肝炎肝硬化、重型肝炎重叠感染常见，急性肝炎最少见。结论 病毒性肝炎中HBV感染最常见，其次为HAV感染；单纯感染、二重感染多见，三重感染少见；重叠感染发生率随病情加重而增加。     

用不同基因型戊型肝炎病毒重组蛋白建立酶联免疫吸附测定一步法

目的 以7种不同基因型和亚型的HEV重组蛋白作为包被抗原,建立HEV抗体检测ELISA一步法.方法 通过方阵滴定法确定包被抗原浓度,确定临界值,并进行敏感度、特异度和热稳定性试验.结果 7种重组抗原混合物(Mix166)最佳包被浓度为1.5 mg/L.抗-HEV IgG检测试剂的批内、批间变异系数分别为8.67%和10.85%,抗-HEV IgM检测试剂的批内、批间变异系数分别为4.56%和5.99%.一步法检测50份HEV RNA阳性血清的HEV IgG和HEV IgM抗体,阳性率均为94%.一步法检测674份健康者血清,52份抗-HEV IgG阳性,3份抗-HEV IgM阳性.一步法检测HEV墨西哥株攻击黑猩猩后收集的系列血清发现,病毒攻击后1～6周抗-HEVIgM阳性,2～76周抗-HEV IgG阳性,而进口试剂盒缺乏对抗-HEV墨西哥株IgG、IgM的反应性.结论 Mix166作为包被抗原建立的HEV抗体ELISA一步法具有较好的敏感性和特异性,可用于HEV感染的诊断.     

广州地区无偿献血者戊型肝炎病毒感染流行病学调查

目的 调查广州地区无偿献血者的戊型肝炎病毒(hepatitis E virus, HEV)感染情况。方法 2017年4月-2018年4月间收集了5 552名广州血液中心无偿献血者的血液样本,采用酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)检测抗-HEV IgG抗体(HEV IgG)、抗-HEV IgM抗体(HEV IgM)和HEV抗原(HEV Ag),采用χ²检验分析年龄、性别、民族、职业和ALT等因素分别与HEV IgG和IgM抗体阳性的相关性,采用多因素Logistic回归分析判辨HEV感染的独立风险因素。结果 HEV IgG、IgM和HEV Ag的阳性率分别为20.05%(1 113/5 552)、0.76%(42/5 552)和0.04%(2/5 552)。年龄和民族是HEV IgG和HEV IgM阳性率的独立风险因素:HEV阳性率随着年龄增长而增大(IgG OR=1.089, 95%CI: 1.080-1.098, P<0.001; IgM OR=1.055,95%CI: 1.028-1.084, P<0.001);壮族的HEV IgG和IgM阳性率(32.69%, 7.69%)高于汉族(19.89%, 0.70%),差异有统计学意义(IgG OR=2.052, 95%CI: 1.103-3.819, P=0.023; IgM OR=12.029, 95%CI: 4.067-35.580, P<0.001)。此外,我们还发现职业是HEV IgG阳性率的独立风险因素,学生是阳性率最低的人群。结论 广州地区无偿献血者中HEV抗体阳性率较高,且在不同人群中感染情况不同,为输血传播HEV的风险评估提供基础数据。     

福建省不同人群中戊型肝炎病毒感染的血清流行病学调查分析

目的了解福建省不同人群中戊型肝炎病毒的感染情况。方法收集普通人群血清2209份,职业危险人群血清1722份,应用双抗原夹心ELISA法检测抗HEV抗体。普通人群由健康体检人员和健康献血者组成,职业危险人群由养鸡场或养猪场的饲养员、屠宰工、兽医、厨师或从事鸡鸭批发者组成,使用SPSS软件比较不同人群的感染率。结果普通人群HEV的阳性率为23.3%,职业危险人群HEV阳性率为33.3%(χ2=48.51,P<0.001)。在职业危险人群中与鸡密切接触者HEV的阳性率显著高于与猪密切接触者。HEV阳性率有随年龄的增长而上升的趋势,在普通人群中男、女性HEV阳性率无显著性差异(P>0.05)。在职业危险人群中男性HEV阳性率显著高于女性。结论普通人群HEV的感染率较高,提示HEV亚临床感染的存在。与猪、鸡密切接触者HEV阳性率高于普通人群,这些数据进一步证明了HEV可能是一种人兽共患病的假设。     

High prevalence of hepatitis E virus antibodies in Sao Paulo,Southeastern Brazil: analysis of a group of blood donors representative of the general population

Brazil is a non-endemic country for hepatitis E virus (HEV) infection with seroprevalence from 1% to 4% in blood donors and the general population. However, data on seroprevalence of HEV in the country are still limited. This study evaluated the prevalence of past or present HEV infection in a group of blood donors representative of the general population of the city of Sao Paulo, Southeastern Brazil. Serum samples from 500 blood donors were tested from July to September 2014 by serological and molecular methods. Anti-HEV IgG antibodies were detected in 49 (9.8%) subjects and categorized age groups revealed an age-dependent increase of HEV seroprevalence. Among the anti-HEV IgG positive subjects, only 1 had anti-HEV IgM while none tested positive for HEV-RNA. The present data demonstrate a higher seroprevalence of anti-HEV IgG than previously reported in the region.     

The Risk of Transfusion-Transmitted Hepatitis E Virus: Evidence from Seroprevalence Screening of Blood Donations

Throughout the world, there has been growing concern over the risk of hepatitis E virus (HEV) transmission via blood transfusion. The present study screened blood donor samples for anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG). The prevalence of HEV infection was assessed on a total of 1,003 archived serum samples obtained from the National Blood Centre, Malaysia. The samples were collected from healthy blood donor from Klang Valley between 2017 and 2018. All samples were tested for IgM and IgG antibodies to HEV using enzyme-linked immunosorbent assays (ELISA). HEV-specific IgG antibodies were detected in 31/1003 (3.1%; 95% confidence interval [CI] 2.1%–4.4%) and IgM in 9/1003 (0.9%; 95% CI 0.4%–1.7%) samples. In bivariate analysis, there was no significant difference in the prevalence of anti-HEV IgG with respect to gender and district of origin. Although not statistically significant, males had higher odds of having anti-HEV IgG than females (odds ratio [OR] = 2.86; 95% CI 0.95–8.64). All anti-HEV IgG positive individuals were people of Chinese descent. Anti-HEV IgG increased significantly with age, from 0.6% (95% CI 0.1%–2.6%) of 18–30-year-old donors to 7.4% (95% CI 2.7%–17.0%) of donors older than 50 years and was highest among non-professional workers (5.3%; 95% CI 2.5%–10.5%). Increasing age and a non-professional occupation remained significant predictors for anti-HEV IgG in the multivariable analysis. Screening of blood donations for HEV in Malaysia is important to safeguard the health of transfusion recipients. The higher rates of HEV infection in blood from older donors and donors who are non-professional workers may provide insights into targeted groups for blood screening.     

Relationships among viral diagnostic markers and markers of liver function in acute hepatitis E

Background  Diagnosis of acute hepatitis E has been based in many clinics predominantly on detection of anti-HEV (hepatitis E virus) antibody. Now, new assays have been developed to detect other HEV markers. Our aim was to investigate the relationships among HEV diagnostic markers and liver function markers in acute hepatitis E. Methods  Seventy serum samples were collected from non-A, non-B, non-C acute hepatitis patients and tested for HEV markers (HEV antigen and RNA and anti-HEV IgM) and markers of liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total iron binding capacity (TBA), γ-glutamyl transferase (GGT), total bilirubin (TBIL), and direct bilirubin (DBIL)]. Partial open reading frame (ORF) 2 sequences from HEV RNA-positive samples were cloned and analyzed. Results  The concordances between HEV antigen and HEV RNA and between HEV antigen and anti-HEV IgM were 77.1% and 72.9%, respectively, with significant correlations, while that between HEV RNA and anti-HEV IgM was 61.4% with no significant correlation. Eleven of 25 samples negative for anti-HEV IgM were positive for HEV antigen. The ALT, AST, ALP, TBA, GGT, TBIL, and DBIL levels did not differ significantly between the anti-HEV IgM-positive and -negative groups. However, the ALT, AST, ALP, TBA, and GGT levels were significantly higher in the HEV antigen-positive group than in the HEV antigennegative group. All of the HEV isolates cloned belonged to genotype 4. Conclusions  HEV antigen was highly correlated with HEV RNA and elevated ALT, AST, ALP, TBA, and GGT levels. Testing for HEV antigen in combination with anti-HEV IgM is useful for the diagnosis of HEV infection.     

Unexpected high prevalence of IgG-antibodies to hepatitis E virus in Swedish pig farmers and controls

Hepatitis E virus (HEV) infections are responsible for large waterborne outbreaks in developing countries. Sporadic cases in the developed world are mainly imported via immigrants and travellers from endemic areas. HEV has been suggested to be a zoonotic infection where pigs may be an important reservoir for the disease and specific swine strains of HEV have been identified which can infect also humans. The aim of this study was to analyse if Swedish pig farmers are more exposed to HEV than persons with other occupations. A total of 115 male pig farmers aged 40-60 y and 108 age- and geographically- matched control subjects were tested for IgG anti-HEV antibodies. No statistical difference in anti-HEV prevalence was noted between pig farmers (13.0%) and control subjects (9.3%). The prevalence of anti-HEV antibodies in the pig farmers and controls was higher than that previously reported among other populations in Europe (<1-9%). Further studies are needed to elucidate the routes for infection of indigenous HEV and if sub-clinical infections with pig associated HEV strains occur in Sweden.     

Seroprevalence of hepatitis E virus in blood donors in Khuzestan Province, Southwest Iran.

OBJECTIVE: To determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors in Khuzestan Province, Iran. Khuzestan is a war stricken area in the southwest of Iran, which shares a land, river, and sea border with Iraq. This region has suffered the heaviest public health system damage of all the Iranian provinces during a 25-year period of war and conflict. METHODS: A cross-sectional study was carried out among 400 urban volunteer blood donors of the regional blood banks, from May to December 2005. Serum samples from healthy blood donors were tested for IgG anti-HEV antibody using a specific enzyme linked immunoassay (ELISA) kit. RESULTS: The prevalence of HEV infection was found to be 11.5% (46/400). All patients were negative for anti-HIV, anti-HBV, and anti-HCV antibodies. The data indicate that 14.6% (38/260) of HEV positive subjects were male, compared to 5.7% (8/140) of females; this difference is statistically significant (risk ratio=2.6, p<0.008). CONCLUSIONS: These findings demonstrate the high prevalence rate of anti-HEV among blood donors, particularly males.