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.     

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.     

Hepatitis E virus infection after haploidentical haematopoietic stem cell transplantation: incidence and clinical course

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6–55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0–5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.     

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.     

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.     

Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil

A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV) infection. All participants answered the questionnaire regarding the sociodemographic characteristics. Serum samples were tested for IgG antibodies to HEV (anti-HEV) by an enzyme linked immunoassay (ELISA). All serum samples positive for anti-HEV IgG and 237 serum samples negative for anti-HEV were also assayed for IgG anti-HAV antibodies by ELISA. Anti-HEV IgG was confirmed in 23/996 samples, resulting in a seroprevalence of 2.3% for HEV infection, similar to previous results obtained in developed countries. No significant association was found between the presence of anti-HEV IgG antibodies and the sociodemographic variables including gender, age, educational level, rural or urban areas, source of water, and sewer system (p > 0.05). Also, no association with seropositivity for anti-HAV IgG antibodies was observed (p > 0.05). Although this study revealed a low seroprevalence of HEV infection in the population evaluated, the results showed that this virus is circulating among the population from Londrina, South Brazil, and point out the need of further studies to define the clinical and epidemiological importance of HEV infection and to identify additional risk factors involved in the epidemiology and pathogenesis of this infection in this population.     

Hepatitis E virus genotype 3 is associated with gallstone-related disease

Abstract

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.

Materials and methods: During 2016–2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.

Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.

Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing 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.     

Epidemic hepatitis E: serological evidence for lack of intrafamilial spread.

INTRODUCTION: Hepatitis E presents as epidemic as well as sporadic disease. Fecal contamination of drinking water results in epidemics of hepatitis E. The extent of intrafamilial spread needs to be assessed employing serological assays. AIMS: To understand the dynamics of intrafamilial spread of the disease. METHODS: The study was conducted using blood samples collected during the 1988 and 1989 epidemics of viral hepatitis in Kudal and Atit villages of Maharashtra state; the epidemics were subsequently shown to be due to hepatitis E virus (HEV). The one-time collection carried out at the end of the Kudal epidemic was from 184 apparently healthy individuals irrespective of family history of jaundice during the epidemic. In the Atit epidemic, 153 family contacts of 49 IgM anti-HEV positive patients were bled. An additional 151 blood samples were collected from apparently healthy individuals irrespective of family history of jaundice during the epidemic. One month later, blood samples were collected from 64 of the 153 family contacts. Relevant history was recorded each time. All serum samples were tested for ALT levels and for IgM and IgG antibodies to hepatitis E virus employing ELISA. RESULTS: IgM anti-HEV positivity among persons with family history of jaundice was not different from those without such a history (8/62 [12.9%] and 11/122 [9%] at Kudal; 9/57 [15.8%] and 22/94 [23.4%] at Atit; p > 0.1). Excluding IgG anti-HEV positive samples from the analysis also yielded non-significant results. Of the 32 follow-up samples collected from family contacts without IgG or IgM antibodies to HEV in the initial blood sample, 31 remained IgM and IgG anti-HEV negative at the end of 1 month. One of the family contacts was found to be IgG anti-HEV positive in the second blood sample. The disease was not related to the index case. CONCLUSION: Intrafamilial spread of HEV is negligible.     

IL-18 discriminates highly frequent hepatitis E virus positive from negative blood donors in Mexico

Introduction and ObjectivesHepatitis E virus (HEV) is not routinely screened in blood banks in low- and middle-income countries, and no specific biomarkers of exposure to this virus have yet been identified. We aimed to identify HEV seropositivity and detect virus RNA among blood donors from Mexico to further correlate risk factors related to infection and levels of interleukin-18 (IL-18) and interferon-gamma (IFN-γ) as potential biomarkers.Materials and MethodsThis cross-sectional, single-center study included 691 serum samples of blood donors obtained in 2019. Anti-HEV IgG and IgM antibodies were detected in sera and the viral genome was screened in pooled samples. A statistical comparison of risk factors for infection, demographic and clinical features was performed; IL-18 and IFN- γ values were tested in sera.ResultsOf all the individuals, 9.4% were positive for anti-HEV antibodies and viral RNA detection was confirmed in one of the pools positive for anti-HEV. From the analysis of risk factors, age and having pets were statistically significant for anti-HEV antibody detection. Seropositive samples showed significantly higher IL-18 concentrations relative to samples from seronegative donors. Interestingly, IL-18 values were similar when HEV seropositive samples were compared to samples from clinically acute previously confirmed HEV patients.ConclusionsOur findings highlight the need to follow up on HEV in blood banks in Mexico and underscore that IL-18 could represent a biomarker of HEV exposure.     

New insights into the natural history of hepatitis E virus infection through a longitudinal study of multitransfused immunocompetent patients in France

Little is known about the natural history of Hepatitis E virus (HEV) infection in immunocompetent individuals. The prevalence, the course of infection and the occurrence of transmission by transfusion were investigated in multitransfused immunocompetent patients/blood donor pairs included in a longitudinal sample repository collection and followed up between 1988 and 2010. Ninety‐eight subjects aged 6–89 years and suffering from acquired haemoglobinopathies were tested for HEV markers (IgM, IgG and RNA) in serial samples collected every 2 or 3 years. Eighteen patients (18.4%) were positive for HEV‐IgG at baseline with a prevalence increasing from 12.5% below 26 years to 32% above 56 years. Nine patients remained IgG positive along the study and nine lost their antibodies after a mean follow‐up of 7.4 years (1–22 years). One seropositive patient showed an increase of IgG level and RNA‐HEV reappearance 1 year after inclusion, suggesting a reinfection and one seroconversion, probably acquired through blood transfusion was observed. This first longitudinal study including immunocompetent individuals confirms that HEV infection is common in Western Europe and that transfusion transmission occurs probably less frequently than expected. In addition, seroreversion and reinfection seem to be common. This suggests that the anti‐HEV may not persist overtime naturally. However, repeat exposure to the virus related to the high prevalence of HEV infection may result in a sustainable specific IgG response.     

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。     

生猪屠宰销售职业人群戊型肝炎病毒感染的危险因素研究

目的　生猪屠宰销售职业人群戊型肝炎病毒的感染情况 ,流行特征及研究工作时间长短与戊型肝炎病毒感染的关系。方法　 2 0 0 3年在浙江省北部地区采用横断面调查方法 ,调查 2 1- 6 1岁生猪屠宰销售人员 189人 ,用ELISA法检测该人群中HEV -IgG和HEV -IgM抗体水平 ,同时调查相关的职业危险因素。 结果　在调查的 189名与生猪屠宰销售相关的职业人群中 ,抗HEV -IgG和抗HEV -IgM阳性者分别为 14 6例和 5例 ,人群总感染率分别为 77 2 5 %和 2 6 5 %。在 189例抗HEV -IgG阳性者中有男性 139例 ,女性为 7例 ,男女的感染率分别为 77 6 5 %和 70 0 0 % ,戊肝感染和性别没有关系。 5例HEV -IgM阳性者都为男性。戊肝感染可见于各个年龄段 ,但流行率分布不平衡 ,差异有显著性 (χ2 =11 2 2 ,P =0 0 11) ,随着年龄的增长感染率有上升的趋势 ,但是到 4 5岁以后戊肝感染率保持在一个相对稳定水平。戊肝感染随着职业人群和猪接触的年限增加而呈现上升趋势 (χ2 =9 5 74 ,P =0 0 0 2 )。结论　浙江省生猪屠宰销售人员的感染率高于当地人群。和密切猪接触是戊型肝炎感染的危险因素之一 ,同时与猪接触的工作年限也是戊肝感染的危险因素。戊肝感染随着年龄的增加而感染率上升 ,4 5岁以后维持一个相对稳定状态。     

Hepatitis Agents with Enteric Transmission – An Epidemiological Analysis

Background: Viral hepatitis is characterized by special clinical, biochemical and serological findings. This study was planned to determine the seroprevalence, epidemiological characteristics and clinical and biochemical findings of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections during an outbreak of jaundice. Materials and Methods: 340 children aged 5–16 years were included. Clinical findings and alanine aminotransferase (ALT) levels were documented. Anti-HAV IgG and IgM in addition to anti-HEV IgG and IgM were determined by microELISA. Results: Clinical findings, high levels of ALT, anti-HAV IgM and IgG, anti-HEV IgM and IgG were present in 6%, 23%, 17%, 100%, 7% and 9% of cases, respectively. The relationship between ALT levels and anti-HAV or anti-HEV IgM seropositivity was significant (p ≤ 0.0001). Conclusion: HAV and HEV infection were both caused by a contaminated water supply. Received: September 21, 2001 · Revision accepted: April 23, 2002 RID="*" ID="*"This study was presented as a poster at 11th European Congress of Clinical Microbiology and Infectious Diseases, Istanbul, Turkey, April 1–4, 2001. A. R. ?rmeci (corresponding author)