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.     

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     

Prevalence of enteric hepatitis A and E viruses in the Mekong River delta region of Vietnam

A study of antibody prevalence for hepatitis A virus (HAV) and hepatitis E virus (HEV) was carried out in southwestern Vietnam in an area adjacent to a known focus of epidemic HEV transmission. The purpose of this investigation was first to provide a prevalence measure of hepatitis infections, and second to determine the outbreak potential of HEV as a function of the susceptible population. Blood specimens collected from 646 persons in randomly selected village hamlets were examined by an ELISA for anti-HEV IgG and anti-HAV IgG. The prevalences of anti-HEV IgG and anti-HAV IgG were 9% and 97%, respectively. There was a significant increase (P < 0.01) in age-specific anti-HEV IgG. A notable increase in anti-HAV IgG prevalence (P < 0.0001) occurred between child populations 0-4 (64%) and 5-9 (95%) years of age. No evidence of familial clustering of anti-HEV IgG-positive individuals was detected, and household crowding was not associated with the spread of HEV. Boiling of water was found to be of protective value against HEV transmission. A relatively low prevalence of anti-HEV indicates considerable HEV outbreak potential, against a background of 1) poor, water-related hygiene/sanitation, 2) dependence on a (likely human/animal waste)-contaminated Mekong riverine system, and 3) periodic river flooding.     

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.     

A case of acute hepatitis E with the travel history to an endemic area]

Hepatitis E is a self-limited and enterically transmitted acute viral hepatitis that occurs from epidemic outbreaks of developing countries and sporadic hepatitis in non-endemic areas. In endemic areas, hepatitis E virus (HEV) is one of the most common causes of acute hepatitis and hepatic failure in pregnancy. Its mortality rate has been reported up to 20%. In non-endemic areas, HEV infection without any travel history is very rare. In Korea, only one case of simple hepatitis E without any travel history to endemic areas was reported. Recently, we experienced a case of acute hepatitis. The patient who had a travel history to India, showed watery diarrhea and high fever. Transaminase level and total bilirubin were increased, and prothrombin time was prolonged. It was positive for IgM anti-HEV and IgG anti-HEV, and showed no evidence of other viral infections or drug ingestion history. In spite of absence of useful test such as seroconversion of IgM anti-HEV and HEV RNA PCR, we diagnosed the case as an acute hepatitis E from his symptom, travel history and initial serologic marker. We report this as a case of hepatitis E infected from endemic areas.     

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.     

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.     

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。     

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。     

戊型肝炎IgM和IgG抗体的临床免疫诊断意义

采用标记第二抗体间接ＥＬＩＳＡ发现，ＩｇＧ－抗ＨＥＶ阳性率２３．５％（４６／１９６），其中ＩｇＭ－抗ＨＥＶ阳性１０例（５．１％）。于１９９３年２月～１９９４年１月继续观察ＩｇＭ－抗ＨＥＶ免疫检出率为６．７％（１０１／１５１５），ＩｇＭ－抗ＨＡＶ检出率为１４．２％（３０２／２１３３）。按月和月／年统计阳性率动态，表明戊型与甲型肝炎全年呈双峰型相伴流行。提示ＩｇＭ－抗ＨＥＶ是诊断现患戊型肝炎的主要免疫指标。     

新疆和田地区人群血清抗HEV水平调查

目的 调查新疆维吾尔族自治区(新疆)和田地区在1986-1989年戊型肝炎流行后,目前人群中血清抗戊型肝炎病毒(hepatitis E virus,HEV)特异性抗体水平及当地HEV感染的状态.方法 应用酶联免疫方法检测抗HEV IgG和抗HEVIgM,检测新疆和田地区1～90岁健康人血清3070例,对抗HEV IgM...     

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.     

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。     

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.     

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.     

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.     

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.