Hepatitis E virus

Hepatitis E virus (HEV) is responsible for major outbreaks of acute hepatitis in developing countries where it was first described as a waterborne disease, transmitted by drinking water contaminated with feces. Attention was focused on HEV in developed countries and its associated diseases in recent years as a result of increasing reports of autochthonous infections. Hepatitis E is the zoonotic cause of these acute infections, and mainly in men over 50 years of age. The clinical manifestations and laboratory abnormalities of hepatitis E infections in immunocompetent patients cannot be distinguished from those caused by other hepatitis viruses. HEV is a major public health concern in immunocompromised patients because their infections can become chronic. The specific etiology of cases of hepatitis E infection can be diagnosed by serological testing and detecting viral RNA. Ribavirin is currently the reference treatment for HEV infections in immunocompromised patients. Several vaccines have proved safe and effective in clinical trials, but none have been approved for use in Europe yet.     

Endemic hepatitis E infections in South-East Hungary

INTRODUCTION: Hepatitis E virus (HEV) one of the most important infectious agent in acute hepatitis in tropical and subtropical areas. Recently, it has been demonstrated that HEV infection also occur in developed countries without travel history. In these regions, transmission thought to be zoonotic. In this work hepatitis E cases are detected in South East Hungary. AIMS: Aims of the authors were the detection of HEV infection in acute hepatitis patients by enzyme-immunoassay (ELISA), and the introduction of clinical and epidemiological features. METHODS: Between January 2001 and October 2004, acute sera samples were tested by serological methods (enzyme-immunoassay for HEV IgM and IgG antibodies) from patients with acute hepatitis observed in Department of Infectology Hospital of Szeged. Samples from non-A-B-C infections hepatitis were tested. CONCLUSIONS: In the mentioned period the detected HEV infections (27) showed a similar incidence as known in other hepatitis in our region. Based upon our results, hepatitis E virus is one of the etiological agent in acute endemic hepatitis in South East Hungary, with special clinical features, which are not entirely similar, found in available literature. The gained data, with their conclusions may have wilder professional interest.     

Genotype Distribution and Sequence Variation of Hepatitis E Virus, Hong Kong

Most acute cases of infection with hepatitis E virus (HEV) in Hong Kong were autochthonous, sporadic, and occurred in older adults. All except 1 isolate belonged to genotype 4; most were phylogenetically related to swine isolates. The epidemiology is similar to that in industrialized countries, where zoonosis is the major source of HEV infection in humans.     

Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.     

Effect of Hepatitis E Virus RNA Universal Blood Donor Screening,Catalonia, Spain, 2017‒2020

Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA–positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons.     

Protective role of humoral immune responses during an outbreak of hepatitis E in Egypt

Although the seroprevalence of hepatitis E virus (HEV) is approximately 80% in adult Egyptians living in rural areas, symptomatic HEV-caused acute viral hepatitis (AVH) is sporadic and relatively uncommon. To investigate the dichotomy between HEV infection and clinical AVH, HEV-specific immune responses in patients with symptomatic and asymptomatic HEV infection during a waterborne outbreak in Egypt were examined. Of 235 acute hepatitis patients in Assiut hospitals screened for HEV infection, 42 (17.9%) were acute hepatitis patients confirmed as HEV-caused AVH; 37 (88%) of the 42 patients were residents of rural areas, and 14 (33%) were from one village (Kom El-Mansoura). Another 200 contacts of AVH cases in this village were screened for HEV and 14 (7.0%), all of whom were family members of AVH cases, were asymptomatic HEV IgM-positive. HEV infections in this village peaked during the summer. Asymptomatic HEV seroconverters had significantly higher levels of epitope-specific neutralising (p=0.006) and high avidity (p=0.04) anti-HEV antibodies than the corresponding AVH cases. In conclusion, naturally acquired humoral immune responses appear to protect HEV-exposed subjects from AVH during an HEV outbreak in Egypt.     

安徽省戊型肝炎基因分型及临床特征研究

目的研究安徽省戊型病毒性肝炎的基因型及其分布特点,为预防和控制戊型病毒性肝炎和疫苗的研制提供科学依据。方法按照戊型病毒性肝炎诊断标准及处理原则（GB17011-1997）于2006年12月～2007年12月从安徽省的4家综合性三甲医院收集戊型病毒性肝炎132例,分析临床特征,其中采集血清50份,用RT-nPCR法检测戊型肝炎病毒基因型。结果HEV RNA阳性率为22%（11/50）,经测序证实为戊型肝炎病毒（Hepatitis Evirus,HEV）的基因序列;用DNA STAR软件分析,11例的病毒株中2例为HEVⅠ型,9例为HEVⅣ型。Ⅳ型中又有ⅣA型3例和ⅣD型6例。结论安徽省急性散发性戊型肝炎的病毒基因型以HEVⅣ型为主,Ⅰ型次之,而Ⅳ型又有不同的亚型,主要为ⅣA和ⅣD型。     

734例急性病毒性肝炎的病原学分析研究

目的研究急性病毒性肝炎病原学的特征,制定科学的预防措施。方法对2004年1月～2008年12月收治的734例急性病毒性肝炎患者,进行血清病原学分型及流行病学研究。结果 734例中,甲、乙、丙、戊型病毒性肝炎分别占15.7%、17.0%、2.4%和35.2%,未分型者占29.7%;发病年龄主要集中在30～69岁,占67.4%,甲型肝炎15～49岁为发病高峰期占62.7%,乙型肝炎发病年龄集中在15～69岁占96.0%,丙型肝炎发病年龄在15～69岁占94.5%,戊型肝炎30～69岁为疾病高发年龄段占61.3%,未分型年龄集中在50～69岁,占74.3%;男性患者519例,女性患者215例,男女性患者之比为2.4∶1,每年1～2季度为发病的高峰季节,分别占27.6%和36.4%;临床分型中急性黄疸型肝炎453例(61.7%),急性无黄疸型肝炎264例(36.0%),重型肝炎17例(2.3%)。结论急性病毒性肝炎以戊型和未分型肝炎类型为常见,急性黄疸型肝炎是主要的临床类型;注意个人卫生及改善卫生条件有助于预防甲型肝炎和戊型肝炎传播,接种甲型肝炎和乙型肝炎疫苗是有效的预防措施。     

Hepatitis E Virus Outbreak among Tigray War Refugees from Ethiopia,Sudan

We report hepatitis E virus (HEV) outbreaks among refugees from Ethiopia in Sudan during June 2021–February 2022. We identified 1,589 cases of acute jaundice syndrome and used PCR to confirm HEV infection in 64% of cases. Implementing vaccination, water, sanitation, and hygiene programs might reduce HEV outbreak risk.     

Molecular epidemiology and genetic history of European-type genotype 3 hepatitis E virus indigenized in the central region of Japan

In Mie prefecture in Japan, 12 cases of sporadic hepatitis E occurred from 2004 to 2011. Mie prefecture is located in the central region of Japan, far from the most prevalent regions of hepatitis E virus (HEV) infection in Japan, the north and northeastern part. These 12 cases did not have any common risk factors of HEV infection. We analyzed the molecular epidemiology of the cases in Mie prefecture. We obtained the nucleotide sequences of the HEV strains and analyzed them with the sequences of other HEV strains by phylogenetic and coalescent analyses. Japan-indigenous genotype 3 HEV strains were divided into two major subtypes, namely, 3a and 3b; one minor subtype, 3e; and a few other unassigned lineages. The Japan-indigenous subtype 3e strains were closely related to European subtype 3e HEV strains and were comparatively rare in Japan; however, eight strains of the 12 cases we examined belonged to subtype 3e, indicating a close phylogenetic relationship, despite the lack of common risk factors. Coalescent analyses indicated that the Mie 3e strains seemed to have intruded into Mie prefecture about 10 years ago. Sporadic acute hepatitis E cases caused by the 3e strains occurred consistently from 2004 to 2011 in Mie prefecture. This is the first report of unexpected persistent occurrence of hepatitis by the European-type genotype 3 HEV, subtype 3e, in a country outside of Europe. Phylogenetic and coalescent analyses traced the history of the indigenization of the Mie 3e strains from Europe. Because hepatitis E cases caused by 3e strains are relatively rare in Japan, molecular evolutionary analyses of HEV infection in Mie prefecture is important for preventing a future hepatitis endemic or epidemic by 3e strains in Japan.     

戊型肝炎病毒的研究概况及进展

戊型肝炎病毒(HEV)是引起戊型肝炎(HE)的病原体。HE呈全球性分布,主要侵犯青壮年,其中孕妇死亡率高达20%。近些年来包括美国、中国、日本、印度在内的一些发达及发展中国家和地区,HE人群感染率呈上升趋势,控制该病刻不容缓。文中针对HEV的研究现状,从HEV的生物学特征、基因分型、细胞模型和动物模型、疫苗及诊断试剂的研究等方面进行综述。     

上海市部分地区散发性戊型肝炎病毒基因型别和发病危险因素研究

目的探讨上海市部分地区急性散发性戊型肝炎（戊肝）病毒（HEV）型别和发病危险因素.方法用巢式RT-PCR方法检测HEV序列,并进行序列的同源性比较分析;同时采取1：2病例对照研究的方法,选取上海市3个区2003-2004年急性散发性确诊戊肝86例住院病例,分别配以本区和其他区健康人群对照组,用单因素和多因素logistlc回归模型进行分析.结果病毒序列分析表明戊肝病例中的HEV病毒序列属于Ⅳ型;单因素分析结果显示居住条件、外出就餐、有海鲜河鲜食用史等均为戊肝发病的危险因素;多因素分析结果显示海鲜（生、炝）食用史（OR=7.048）是戊肝感染 的危险因素.结论上海市部分地区散发性HEV流行株以Ⅳ型病毒株为主,海鲜（生、炝）食用史等是戊肝发病的危险因素.     

杭州地区妊娠晚期孕妇病毒性肝炎感染的调查研究

目的:调查杭州市2958例妊娠晚期孕妇乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)、丁型肝炎病毒(HDV)、戊型肝炎病毒(HEV)的感染状况。方法:对杭州市2958例妊娠晚期孕妇的血清乙型肝炎标志物、HCV抗体、HDV抗体、HEV抗体的检测结果进行统计分析。结果:2958例妊娠晚期孕妇中乙型肝炎总感染率40.16%,HCV抗体阳性率0.40%,HDV抗体阳性率0.20%,HEV抗体阳性率2.60%。结论:杭州地区妊娠晚期孕妇病毒性肝炎的感染以乙型肝炎位居第一、戊型肝炎次之,丙型肝炎及丁型肝炎感染率较低。应加强育龄女性易感人群乙肝疫苗的预防接种,开展和实施有效的预防措施来防止病毒性肝炎的感染,提高新生人口的素质。     

Hepatitis E virus infection in HIV-infected persons

To determine whether hepatitis E virus (HEV) is a cause of hepatitis among HIV-infected persons, we evaluated 1985-2009 data for US military beneficiaries. Evidence of acute or prior HEV infection was detected for 7 (4%) and 5 (3%) of 194 HIV-infected persons, respectively. HEV might be a cause of acute hepatitis among HIV-infected persons.     

Hepatitis E: An emerging disease

Currently, the infection with the hepatitis E virus represents the most frequent cause for acute hepatitis and jaundice in the world. According to WHO estimations, around two billion people, representing one third of the world’s population, live in endemic areas for HEV and, therefore, are at risk of infection. In developed countries, the circulation of the virus in both human and animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate is low compared to that of developing countries where outbreaks of acute hepatitis transmitted via the fecal-oral route are originated, more frequently in the flooding season or after natural disasters, combined with deficient sanitary conditions.There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are isolated in all human epidemic outbreaks in developing countries, while genotypes 3 and 4 are isolated not only in humans but also in animals, in both developing and industrialized countries. These data support genotypes 3 and 4 having zoonotic nature. The diagnosis of this disease is based in the detection of anti-HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods. However, the method that best confirms the diagnosis is the RT-PCR, which detects HEV RNA in blood serum and also provides the genotype. The clinical course is generally that of an acute hepatitis which in some cases may require hospitalization and that, in transplant patients or HIV infected individuals can become a chronic hepatitis. Furthermore, the virus constitutes an important risk for pregnant women. The hepatitis E can present a wide range of symptoms, from a subclinical case to chronic liver disease with extrahepatic manifestations. For this reason, the diagnostic is challenging if no differential diagnosis is included. There is no specific antiviral drug for hepatitis E, but satisfactory results have been observed in some patients treated with pegylated interferon alfa2a and/or ribavirin.This revision is an update of all the molecular, epidemiological, clinic and preventive knowledge on this emergent disease up to date.     

Role of hepatitis E and other hepatotropic virus in aetiology of sporadic acute viral hepatitis: A hospital based study from urban Delhi

Major hepatotropic virus continues to be an important cause of acute viral hepatitis (AVH) in developing countries like India. While epidemics of AVH have been well studied few serious sporadic cases from developing countries have been reviewed. We studied prospectively 75 cases of sporadic AVH who reported to our hospital and were evaluated for the presence of various hepatotropic viruses. The seroprevalence of IgG anti-HEV antibodies was studied in the general population as a control. We found 53.3% (40/75) of sporadic AVH cases were due to hepatitis E virus while 11% (8/75) were due to hepatitis B virus. Hepatitis C virus was responsible for 8% (6/75) of the sporadic AVH cases and hepatitis A was found in 5% (4/75) of the cases. No causative agent was found in 23% (17/75) of the sporadic AVH cases. The sporadic AVH cases due to HEV were not clinically or biochemically not different from AVH due to other viruses. We found a high prevalence of IgG anti-HEV in 35.6% (178/500) among the general population of urban Delhi. The study suggested that hepatitis E was the most common cause of sporadic AVH in urban Delhi. High seroprevalence of IgG anti-HEV antibodies in the general population and amongst the sporadic AVH cases suggests that it is unlikely to be protective antibody. IgM anti-HEV positive serology is considered diagnostic of acute hepatitis E infection in India, where hepatitis E is endemic.     

HEV Infection as an Aetiologic Factor for Acute Hepatitis: Experience from a Tertiary Hospital in Bangladesh

Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004–December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 μmol/L, raised serum transaminases, and prothrombin time ≥3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in cirrhotics in Bangladesh. Sewerage contamination of piped water following floods may contribute to the higher incidence of HEV infection.Key words: Hepatitis, Hepatitis E infections, Hepatitis E virus, Retrospective studies, Bangladesh     

3种戊型肝炎病毒抗原检测血清抗—HEV IgG的比例研究

目的：用3种抗原检测国家戊型肝炎参比血清和急性戊型肝炎病人血清抗－HEV IgG。方法：人工合成戊型肝炎病毒（HEV）ORF2和ORF3多肽抗原（BMU抗原）检测参比血清的灵敏度（90．0％），特异度（100．0％）和符合率（97．5％）均高于杆状病毒表达的HEV重组蛋白空粒子抗原（JP抗原）（分别为70．0％，93．3％和87．5％）及大肠杆菌表达的重组蛋白抗原（HKU抗原）（分别为70．0％，90．0％和85．0％），检测84例急性戊型肝炎病人血清抗－HEV IgG，用BMU抗在检测抗－HEV IgG的阳性率为1000％（84／84），高于JP抗原（83／84，98．8％）和HKU抗原（71．84，84．5％）。结果：不同HEV抗原检测国家参比血清和急性戊型肝炎病人血清抗－HEV IgG的灵敏度和特异性不同，其差异主要与编码该3种抗原的HEV基因片段不同有关，ORF3抗原在检测急性HE病人中具有重要意义。联合应用ORF2和ORF3抗原可提高抗－HEVIgG检出率，结论：抗－HEV IgG ELISA诊断试剂至少应包括ORF2和ORF3 2种抗原。     

Hepatitis E virus and neurologic disorders

Information about the spectrum of disease caused by hepatitis E virus (HEV) genotype 3 is emerging. During 2004-2009, at 2 hospitals in the United Kingdom and France, among 126 patients with locally acquired acute and chronic HEV genotype 3 infection, neurologic complications developed in 7 (5.5%): inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Three cases occurred in nonimmunocompromised patients with acute HEV infection, and 4 were in immunocompromised patients with chronic HEV infection. HEV RNA was detected in cerebrospinal fluid of all 4 patients with chronic HEV infection but not in that of 2 patients with acute HEV infection. Neurologic outcomes were complete resolution (n = 3), improvement with residual neurologic deficit (n = 3), and no improvement (n = 1). Neurologic disorders are an emerging extrahepatic manifestation of HEV infection.