献血员戊型肝炎病毒亚临床感染情况调查

目的了解献血员中戊型肝炎病毒(HEV)亚临床感染情况。方法对2002年7～8月向北京市血液中心义务献血的所有人员进行整群抽样，检测抗-HEV IgM和IgG抗体。结果北京献血员中抗-HEV IgM阳性率为1．74％，其丙氨酸氨基转移酶(ALT)异常比例高于抗-HEV IgM阴性献血员。ALT异常与HEV相关的比例为2．68％，与HBV相当，但高于丙型肝炎病毒。结论献血员中存在HEV亚临床感染者，并且是献血员中ALT异常的原因之一。     

Significance of serum IgA in patients with acute hepatitis E virus infection

AIM: To study the significance of serum anti-hepatitis E virus (HEV) IgA in patients with hepatitis E. METHODS: A new method was established to assay anti-HEV IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA. RESULTS: The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20±11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90±15 d and 120±23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA (P <0.05). CONCLUSION: The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.     

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。     

Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions.

AIM: To investigate the prevalence of infection with hepatitis viruses in children with thalassemia receiving multiple blood transfusions. METHODS: Sera from 50 children with thalassemia aged 5-15 years (30 boys), who had each received over 80 units of blood, were evaluated for the presence of markers for hepatitis A virus (HAV; IgG and IgM anti-HAV), hepatitis B virus (HBV; HBsAg, and IgG and IgM anti-HBc), hepatitis C virus (HCV; IgG and IgM anti-HCV, and HCV RNA) and hepatitis E virus (HEV; IgG and IgM anti-HEV). IgM anti-hepatitis D virus (HDV) was looked for only in HBsAg or IgM anti-HBc positive sera. RESULTS: No child had evidence of recent HAV or HDV infection. IgG anti-HAV was positive in 12 children. One patient had acute HBV infection. Nine patients were HBsAg-positive. HCV infection was present in 15 cases; six of them were HCV RNA positive, and three had superinfection with hepatitis B. Recent HEV infection was present in 5 cases. CONCLUSION: Thalassemic patients receiving multiple blood transfusions often acquire hepatitis B (20%) and C (30%) infections. Recent hepatitis E infection was documented in 10% in this one-point study.     

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。     

Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient

Acute hepatitis E virus (HEV) infection is a self-limiting symptomatic or asymptomatic disease. However, as recently observed, it can manifest itself as chronic hepatitis in patients receiving solid organ transplants as well as in patients with HIV infection or severe hematologic disorders. Here, we describe the clinical course of a 73-year-old male patient in whom HEV transmission occurred after receiving a HEV-infected liver from a donor with occult HEV infection, whereby the patient had tested negative for HEV RNA and anti-HEV antibodies shortly before explantation. Anti-HEV IgG, IgM, and HEV RNA were detected in the first tested serum sample of the liver recipient obtained 150 days after liver transplantation and remained positive (earlier samples after OLT were not available). Liver cirrhosis developed within 15 months and the patient died of septic shock. Based on phylogenetic analyses of the donor and recipient's HEV strains, we were able to prove that the occult HEV infection was transmitted via the graft.     

Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area

AIM: To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally. METHODS: We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions. RESULTS: In our retrospective study, markers of acute HEV infection (IgM anti-HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71-54.70]). All 13 HEV-infected patients had been transfused at least once in a 3-month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti-HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti-HEV as well) and two of 25 control patients. Post-transfusion HEV infection developed in three of 22 susceptible (IgG anti-HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti-HEV positive (3/4). In contrast, none of the non-transfused patients developed HEV infection during the follow-up period. CONCLUSION: Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.     

Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E virus

Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern China. However, the evaluation of antibodies to HEV during consecutive time periods after infection has not been reported. We utilized enzyme immunosorbent assay (ELISA) to detect IgM and IgG anti-HEV in consecutive serum specimens from patients with acute hepatitis E and compared that data with detection rates of IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be detected as early as 4 days after onset of disease symptoms in some patients. The detection rate of IgM anti-HEV is significantly higher in specimens collected within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks after onset (67.6%) (P<0.005). IgM anti-HEV had a similar pattern to IgM anti-HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti-HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P<0.005). One should be cautioned against making a diagnosis of HEV infection solely by the currently available assays for IgG anti-HEV. In conclusion, IgM anti-HEV can be used as a reliable and sensitive marker for recent HEV infection, but serum specimens should be collected within 4 weeks after onset of symptoms to avoid false-negative results. In contrast, we should be aware of the failure to develop IgG anti-HEV in some patients. These patients carry the risk of reinfection.     

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.     

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.     

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     

Clinical Significance of Anti-HEV IgA in Diagnosis of Acute Genotype 4 Hepatitis E Virus Infection Negative for Anti-HEV IgM

Anti-HEV IgM is a diagnostic for recent or ongoing HEV infection. However, some patients with acute hepatitis E (AHE) negative for anti-HEV IgM in acute period were often observed in clinical practice. In this study, we constructed the anti-HEV IgA indirect ELISA assay to evaluate the significance of anti-HEV IgA. The specificity of anti-HEV IgA was 99.6%. Among 245 AHE patients, 84 samples from 84 patients were positive for HEV RNA. The positive rate of anti-HEV IgA, anti-HEV IgM and anti-HEV IgG in 84 samples positive for HEV RNA was 96.3, 97.6, and 88.1%, respectively, and no sample was negative for anti-HEV IgA and anti-HEV IgM simultaneously. Among 245 AHE patients, we found nine samples collected from nine patients in acute period were negative for anti-HEV IgM but positive for anti-HEV IgA and two samples were positive for HEV RNA. Detection of anti-HEV IgA can be a useful supplement for diagnosis of acute HEV infection especially in patients negative for anti-HEV IgM.     

Prevalence of hepatitis E virus in Egyptian children presented with minor hepatic disorders

Hepatitis E virus (HEV) is considered as one of the common causes of particular hepatitis in developing countries. It is transmitted in a fecal-oral manner. It causes sporadic infections and large epidemics. To estimate the prevalence of anti-HEV IgG and IgM antibodies to ORF3 peptide of Hepatitis E virus genome in an age of children, study subjects (100 children) between 6 months and 10 years with minor, hepatic illnesses were recruited for the study during the period from September 2004 to September 2005. Serum anti-HEV IgG and anti-HEV IgM antibodies were screened in all subjects, anti-HEV IgM antibodies were assayed as an indicator of recent infection. Serum transaminases (AST and ALT) were estimated in positive subjects. Out of 100 subjects recruited, 26 subjects (26%) demonstrated anti-HEV IgG and 6 (6 %) were anti-HEV IgM and IgG positive. Anti-HEV IgG were present since the first year of age till 10 years of age and increased with advancing age. Serum transaminases were raised in one (17%) of subjects with anti-HEV IgM antibodies. CONCLUSIONS: Children are susceptible to HEV infection since early infancy. Seropositivity to HEV antibodies increased by over 2 times beyond 4 years of age as compared to younger age.     

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution.     

Seroepidemiology and genetic characterization of hepatitis E virus in western Yunnan Province

Objective:To investigate the seroepidemiology and genetic characterization of hepatitis E virus(HEV) in western Yunnan Province.Methods:Questionnaire survey was conducted among1638 residents in western Yunnan Province using stratified sampling method.Enzyme-linked immunosorbent assay was used to detect serum anti-HEV IgG and IgM.HEV RNA was extracted from patients with serum anti-HEV IgM positive.The open reading flame 2(ORF2) of HEV that was amplified by nested RT-PCR was sequenced and compared with standard HEV genotypes 1-4.Results:Serum anti-HEV positive was found in 13.929(228/1638) residents.The HEV infection rate in males was significantly higher than that in females with a ratio of 1.47(P0.01).20-30 and30-40 years old young men showed the highest incidence.20.57%and 20.78%.respectively.While10-20 and 20-30 years old young women exhibited the highest infection rate,11.85%and 15.60%,respectively.According to occupation,the highest HEV infection rate was observed in farmers(20.35%) and migrants(16.50%).We isolated 10 individual HEV isolates from 31 patients with serum anti-HEV IgM positive.Homology analysis and phylogenetic analysis indicated that these10 HEV isolates belonged to HEV genotype 4 with the homology of 78.65%-94.71%.Conclusions:The HEV infection rate is high in western Yunnan Province.HEV genotype 4 is the leading cause of HEV infection and young farmers and migrants are the main infected population.     

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.     

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.     

Etiology of endemic viral hepatitis in urban North India

This study was carried out to determine the presence of markers of hepatitis viruses in patients with acute liver disease. Coinfection of HAV, HBV, HCV, and HEV was studied. Sera from 306 patients with a clinical diagnosis of acute liver disease were tested for the presence of anti-HAV antibody, HBsAg, anti-HBc antibody, anti-HBs antibody, anti-HCV antibody and IgM anti-HEV antibody by ELISA. Liver function tests were correlated with the presence of infection. Of the 306 cases, 7 (2.3%) had IgM anti-HAV, 9 (2.9%) had IgM anti-HBc, 37 (12.1%) had HBsAg, 84 (27.4%) had anti-HBs, 10 (3.3%) were HCV infected and 63 (20.6%) had IgM anti-HEV. There was no significant difference in the clinical and liver function profiles of infected and uninfected patients. Similarly, no difference was observed in cases coinfected with more than one virus compared with those infected with a single pathogen. HEV had the highest prevalence amongst our cases. There was no difference in the clinical profiles of patients with non-A, non-B, non-C, non-E hepatitis by antibody assays and testing for viremia could be helpful in making the correct diagnosis.