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。     

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。     

戊型肝炎及重叠乙型肝炎感染患者丙氨酸转氨酶变化

目的　观察戊型肝炎及重叠乙型肝炎感染患者丙氨酸转氨酶 (ALT)变化。方法　将戊型肝炎抗体阳性及重叠乙型肝炎感染患者 2 73例分为 5组。A组 12 7例 ,为戊型肝炎病毒 (HEV) IgG阳性 ;B组 9例 ,为HEV IgM阳性 ;C组 64例 ,为HEV IgM和HEV IgG均阳性 ;D组 3 2例 ,为HEV IgM和HEV IgG均阳性并重叠乙型肝炎感染 ;E组 41例 ,为HEV IgG阳性并重叠乙型肝炎感染。另选戊型肝炎抗体阴性的非乙型肝炎患者 5 0 0例作为对照组。用速率法测定各组ALT值。结果　各组ALT异常增高百分率及异常增高者ALT值分别为 :A组 2 1例 ( 16.5 %) ,ALT( 183± 89)U /L ;B组 3例 ,ALT( 2 0 3± 112 )U /L ;C组 16例 ( 2 5 .8%) ,ALT( 2 17± 119)U/L ;D组 11例 ( 3 4.4%) ,ALT( 2 3 4± 12 8)U/L ;E组 13例 ( 3 1.7%) ,ALT( 2 10± 98)U/L ;对照组 5 1例 ( 10 .2 %) ,ALT( 112± 68)U/L。戊型肝炎抗体阳性各组ALT异常增高率与对照组间差异有显著性 (P <0 .0 5 ) ,戊型肝炎抗体阳性各组ALT异常增高者ALT值与对照组间差异有显著性 (P <0 .0 5 )。结论　戊型肝炎抗体阳性组ALT异常增高率和增高者ALT值均较对照组有明显增高 ,HEV IgM阳性或重叠乙型肝炎感染较单纯HEV IgG阳性者 ,ALT增高明显     

戊型肝炎病毒感染后自身免疫性肝炎一例

患者 ,男性 ,3 1岁。患者于 1997年 9月无诱因地出现乏力、纳差、厌油 ,尿黄如浓茶色 ,当时查血丙氨酸转氨酶 (ALT )64 0U /L ,门冬氨酸转氨酶 (AST) 5 60U /L ,总胆红素 (TBil) 86.4μmol/L ,直接胆红素 (DBil) 5 1.2 μmol/L ,碱性磷酸酶 (ALP)及r 谷氨酰转肽酶 (GGT)均高于正常 (具体值不详 ) ,乙肝表面抗原 (HBsAg)阴性 ,乙肝病毒 (HBVDNA)阴性 ,甲肝病毒抗体 (抗HAV IgM )阴性 ,丙肝病毒抗体 (抗HCV )阴性 ,戊肝病毒抗体(抗HEV IgM )阳性。诊断为病毒性肝炎 ,戊型急性黄疸型。经保肝、降酶和退黄等治疗 1个月后肝功…     

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。     

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。     

74例慢性乙型肝炎患者急性发作临床特征分析

目的探讨慢性乙型肝炎急性发作临床特点,为诊断、治疗慢性乙型肝炎急性发作提供循证医学证据。方法回顾性分析海口市人民医院2011年1月-2015年10月确诊的74例慢性乙型肝炎急性发作患者的临床资料。将纳入患者分为HBe Ag阳性组(n=51)和阴性组(n=23)。计量资料两组间比较采用t检验,计数资料组间比较采用χ2检验。结果慢性乙型肝炎急性起病,ALT水平为523~2940 U/L,表现为黄疸型肝炎64例(86.49%),4周内临床治愈65例(87.84%)。HBe Ag阳性组与HBe Ag阴性组基线ALT、AST、HBV DNA水平差异均无统计学意义(P值均0.05),但HBe Ag阴性组患者的TBil水平[(141.1±132.9)μmol/L]较阳性组[(80.1±68.8)μmol/L]高,差异有统计学意义(t=2.745,P=0.007)。结论慢性乙型肝炎急性发作发病过程类似于急性乙型肝炎,HBe Ag阴性患者的TBil水平较高,肝细胞损伤较重。     

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。     

血浆透析滤过治疗时间对肝衰竭治疗效果的影响

目的探讨血浆透析滤过(PDF)治疗时间的长短对肝衰竭患者肝功能的影响以及对治疗后肝功能反弹的影响。方法选择2015年1月-2016年12月首都医科大学附属北京佑安医院收治的肝衰竭患者101例,按照治疗时间分为2组,治疗4 h组77例,治疗6 h组24例,均在内科治疗的基础上行人工肝治疗。观察2组治疗前后ALT、AST、TBil、DBil下降幅度及治疗后24 h、治疗后72 h的ALT、AST、TBil、DBil反弹幅度。计量资料2组间比较采用t检验,计数资料组间比较采用χ2检验。结果 2组患者治疗过程中血流动力学稳定,无不良事件发生,部分患者诉平卧时间长,感觉乏力,4 h组5例不耐受,不耐受率6.5%,6 h组10例,不耐受率41.7%,显著高于4 h组(χ2=17.90,P0.01)。PDF治疗后,2组ALT、AST、TBil、DBil下降幅度差异均无统计学意义(t值分别为2.53、-4.48、-1.52、-0.47,P值均0.05)。2组治疗后24 h ALT、AST、TBil、DBil反弹幅度差异均无统计学意义(t值分别为-0.236、-1.251、-1.251、0.943,P值均0.05)。2组治疗后72 h ALT、AST、TBil、DBil反弹幅度差异均无统计学意义(t值分别为-0.7000、0.596、-1.530、1.837,P值均0.05)。结论 PDF治疗不同时间效果相似,安全性相仿,因此常规可采用4 h治疗时间以增加患者耐受性。     

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.     

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.     

抗戊型肝炎病毒IgG和IgM抗体对诊断急性戊型肝炎的意义

目的 探讨抗戊型肝炎病毒（ＨＥＶ）ＩｇＧ和ＩｇＭ抗体对诊断急性戊型肝炎（ＨＥ）的意义。方法 应用酶联免疫法（ＥＩＡ）检测我国７个城市共计１４３例散发性ＨＥ病人急性期血清和其中５６例病人的３５９份系列血清,以及４只实验感染ＨＥＶ猕猴的６８份系列血清的抗－ＨＥＶＩｇＭ和ＩｇＧ。结果 ７个城市１４３例散发性ＨＥ病人急性期血清抗－ＨＥＶＩｇＧ阳性率为１００．０％,明显高于抗－ＨＥＶＩｇＭ（７３．４％）,９     

Detection of hepatitis E virus RNA and genotype in Bangladesh

Background/Aims:  Hepatitis E virus (HEV) in Bangladesh has not been adequately documented. We report HEV RNA and genotype detection in Bangladesh.
Methods:  In total, 82 samples were used; 36 sporadic acute hepatitis (AH), 12 fulminant hepatitis (FH), 14 chronic liver disease (CLD) and 20 from an apparently healthy population (HP) positive for both immunoglobulin (Ig) M and IgG specific anti-HEV antibodies (anti-HEV). The male/female ratio was 61/21, ages 12–67 (mean 30.4) years. RNA was extracted, transcribed to cDNA and amplified in nt 6345–6490 (ORF2) of HEV. Nucleic and amino acid sequences were determined. Homology comparison between Bangladesh clones and other representative HEV clones and phylogenetic tree analyses were done. Relations between HEV RNA-positivity and clinical factors were analyzed.
Results:  HEV RNA was positive in 9/36 (25.0%) of AH cases, 4/12 (33.3%) FH, 3/14 (21.4%) CLD and 0/20 (0%) HP samples; total 16/82 (19.5%). Four factors correlated significantly with HEV RNA-positivity (Mann-Whitney U test); alanine aminotransferase (ALT) ( P  = 0.0229), aspartate aminotransferase (AST) ( P  = 0.0448), and titers of IgG ( P  = 0.0208) and IgM ( P  = 0.0095) specific anti-HEV. The 16 HEV clones were divided mainly into two groups, A and B, including six different cDNA sub-groups.
Conclusion:  HEV RNA was found in sporadic AH and FH and sub-clinical CLD cases, but not in HP. HEV RNA-positivity was significantly related to values of ALT and AST and titers of IgG and IgM specific anti-HEV, with IgM specific anti-HEV showing the most significant relationship. All clones were genotype I, which is prevalent in South Asia.     

Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers

Summary.  Infection with the hepatitis E virus (HEV) causes a self-limiting acute hepatitis. However, prolonged viremia and chronic hepatitis has been reported in organ transplant recipients. Vertically transmitted HEV infection is known to cause acute hepatitis in newborn babies. The clinical course and duration of viremia in vertically transmitted HEV infection in neonates in not known. We studied 19 babies born to HEV infected mothers. Babies were studied at birth and on a monthly basis to evaluate clinical profile, pattern of antibody response and duration of viremia in those infected with HEV. Fifteen (78.9%) babies had evidence of vertically transmitted HEV infection at birth (IgM anti-HEV positive in 12 and HEV RNA reactive in 10) and three had short-lasting IgG anti-HEV positivity because of trans-placental antibody transmission. Seven HEV-infected babies had icteric hepatitis, five had anicteric hepatitis and three had high serum bilirubin with normal liver enzymes. Seven babies died in first week of birth (prematurity 1, icteric HEV 3, anicteric HEV 2 and hyperbilirubinemia 1). Nine babies survived and were followed up for clinical, biochemical, serological course and duration of viremia. Five of 9 babies who survived were HEV RNA positive. HEV RNA was not detectable by 4 weeks of birth in three babies, by 8 weeks in one and by 32 weeks in one. All surviving babies had self-limiting disease and none had prolonged viremia. Thus HEV infection is commonly transmitted from mother-to-foetus and causes high neonatal mortality. HEV infection in survivors is self-limiting with short lasting viremia.     

Epidemic of hepatitis E in a military unit in Abbotrabad,Pakistan

An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease), but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to be 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development.     

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。     

International collaborative survey on epidemiology of hepatitis E virus in 11 countries

We conducted seroepidemiological studies on antibody prevalence to hepatitis E virus (HEV) in 5,233 sera from 11 countries to ascertain the present state of HEV infection on a global basis. The prevalence of anti-HEV IgG increased with age in these tested countries, but the rate of antibody positivity was over 20% in the 16-30 year-old group in most of the participating countries, except for Japan, the USA, and Spain. Of patients with acute hepatitis of unknown etiology from Nepal, 56% (14/25) were positive for the IgM class of anti-HEV antibody. In addition, HEV RNAs in the serum from 3 Nepali patients who had the IgM antibody were detected by nested PCR and all of the HEV genes isolated belonged to genotype 1. Our results indicate that HEV is spreading worldwide, not only in developing countries, but also in more industrialized countries than previously thought.