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Background & Aims: Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC)., Methods: Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion., Results: In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001)., Conclusions: In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis., Lay Summary: The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%., Objectives: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK., Methods: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%., Results: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses., Conclusions: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.

Hepatitis E virus infection during pregnancy can have severe consequences for mother and child, such as vertical transmission, fulminant hepatic failure, even foetal or maternal mortality. The aim of this systematic review is to describe maternal, foetal and neonatal case-fatality rates as well as the prevalence of adverse outcomes in relation to hepatitis E virus infection during pregnancy. A systematic literature search was performed in Pubmed, Embase, Cochrane and CINAHL. Search terms included Pregnant, Women, Maternal, Infant, Foetal, Neonatal and Hepatitis E virus. Data were extracted using predefined data collection forms. All studies were quality assessed, either by the Newcastle-Ottawa Scale or by an adapted assessment scale for cross-sectional studies. We found 23 eligible studies, all observational, which were included in this systematic review with a total of 1338 cases. The median maternal, foetal and neonatal case-fatality rates were 26% (IQR 17%-41%), 33% (IQR 19%-37%) and 8% (IQR 3%-20%), respectively. Adverse outcomes such as fulminant hepatic failure, preterm labour, postpartum haemorrhage, low birth weight and vertical transmission were reported. The two studies that reported the highest prevalence of fulminant hepatic failure also reported the highest case-fatality rates. The median prevalence of fulminant hepatic failure was 45.3%. This systematic review found a high case-fatality rate among pregnant women infected with hepatitis E virus and a high rate of adverse outcomes among these women and their children. The results from this review mainly apply to hospital settings and symptomatic pregnant women from endemic countries., (© 2019 John Wiley & Sons Ltd.)

Background & Aims: The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation., Methods: We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity., Results: The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%)., Conclusion: Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution., Lay Summary: Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) genotypes 1 and 2 are responsible for the majority of acute viral hepatitis infections in endemic areas in South Asia and sub-Saharan Africa. In addition to frequent sporadic illnesses throughout the year, these viruses often cause large epidemics in association with monsoon rains in Asia or during humanitarian crises in Africa. Clinical hepatitis commonly involves adults more often than young children, with an overall mortality of ∼1%. However, the mortality among pregnant women is often 30% or higher. HEV infection in pregnant women frequently leads to infant mortality or premature delivery. Hepatitis E is an important, yet largely neglected, global public health problem., (Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.)

Hepatitis E virus (HEV) infection in developing countries is associated with poor hygiene, lack of clean drinking water, and inadequate sanitation. In this study, we report the first case investigation and describe the present situation of HEV outbreak within displaced persons camps in the Diffa region, Republic of Niger. The investigation showed the outbreak to be closely linked to unclean water supply, low hygiene, and sanitation facility standards. Between January and September 2017, a total of 1,917 HEV suspect cases were recorded from which 736 (38.4%) have been confirmed positive for HEV by reverse transcription polymerase chain reaction and enzyme linked immunosorbent assay. Overall, 38 (1.9%) deaths were recorded, including 17 (44.7%) pregnant women. The ongoing outbreak highlights poor drinking water quality and sanitation conditions in displaced persons camps in the Diffa region. Disease containment and patient care activities, particularly for pregnant women, may have resulted in decreased transmission of infection and deaths.

Background: The epidemiology of acute hepatitis A and E has been changing over the last 2 decades. The impact of concomitant chronic hepatitis B (CHB) on clinical outcomes remains unclear. We aimed to evaluate the morbidity and mortality of patients with acute hepatitis A or E with and without underlying CHB., Methods: We identified consecutive patients with acute hepatitis A or E based on hepatitis serology from the electronic medical records of the Hospital Authority of Hong Kong from January 2000 to December 2016. Hepatic events, all-cause mortality, and liver-related mortality within 30 days of the diagnosis of acute hepatitis were evaluated., Results: The cohort included 1068 cases of acute hepatitis A and 846 cases of acute hepatitis E. More patients with acute hepatitis E than those with acute hepatitis A had underlying CHB (13.5% vs 8.0%; P < .001). Patients with hepatitis E had more all-cause mortality (3.9% vs 0.6%; P < .001), liver-related mortality (2.0% vs 0.3%; P < .001), and hepatic events (2.8% vs 0.3%; P < .001) within 30 days from diagnosis. In patients with acute hepatitis E, underlying renal failure (adjusted hazard ratio [aHR], 3.90; P < .001) and age ≥50 years (aHR, 3.25; P = .036) were associated with 30-day all-cause mortality, whereas CHB (aHR, 3.34; P = .02) was associated with 30-day liver-related mortality., Conclusions: The mortality is higher in patients with acute hepatitis E than in those with hepatitis A. Coexisting CHB is the independent risk factor for liver-related mortality in patients with acute hepatitis E.

Background: Hepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination., Methods: We analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007-2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies., Results: Under baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively. Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16-65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%., Conclusions: HEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women., Competing Interests: The authors have declared that no competing interests exist.

Introduction and Aim: Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and King's College Hospital Criteria (KCH) for predicting outcome in ALF., Materials and Methods: All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported., Results: Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score ≥ 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality., Conclusions: Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis- related ALF.

Hepatitis E infection (HEV) in pregnant females, especially in the third trimester is associated with poor foetomaternal outcomes. However, the mechanisms of severe liver injury remain obscure. In a recent HEV outbreak in North India, six pregnant females were detected to be positive for HEV infection with concomitant hepatitis A infection in three pregnant females. None of the pregnant females were positive for hepatitis B or hepatitis C infection. The mortality was 50% in pregnant females. In an outbreak, besides, testing for hepatitis markers and understanding the pathogenesis of HEV infection in pregnancy, improving basic hygienic standards is of utmost importance., Competing Interests: There are no conflicts of interest

Hepatitis E virus (HEV) is endemic in Pakistan. Although otherwise asymptomatic, HEV infection becomes fatal in pregnancy, with considerable maternal and fetal morbidity and mortality. We conducted a descriptive study from April to October 2015 in 10 tertiary care hospitals throughout Pakistan to determine maternal and fetal morbidity and mortality in HEV-positive pregnant women with acute jaundice or raised liver function tests. Twenty-one of 135 women were HEV positive and in 3rd trimester except for 1 in 1st trimester. Overall prevalence of HEV in pregnancy was 0.19%. Ten women were artificially induced, 3 had premature labour, 4 delivered spontaneously (full term), 3 died and there was 1 intrauterine death. One woman had a home abortion before coming to hospital. There were 7 perinatal infant deaths: 4 intrauterine, 3 stillbirths and 1 abortion. Maternal mortality was significantly associated with delivery, as 17 mothers who lived went into labour spontaneously or were artificially induced, whereas 3 women who continued their pregnancy and did not deliver, died. Case fatality rate of HEV infection in pregnancy was 14.2%.

Purpose of Review: The purpose of this chapter is to review the literature published in the past 10 years with focus to the best literatures published since 2015 regarding chronic hepatitis E virus (HEV) infection in patients who received solid organ transplantation., Recent Findings: Diagnosis of this disease relies primarily on identification of HEV RNA in serum and more recently in stool as way of predicting relapse and guide therapy duration. Current management focuses primarily on primary prevention and supportive care, because additional research is needed to identify efficacious pharmacologic therapy, though use of ribavirin has shown promise in case series in treatment of some genotypes., Summary: Infection with HEV is a rare but significant infection in organ transplant recipients. Though initially thought to be a primarily self-limiting infection, cases of chronic and persistent infection are increasing, being recognized both in developing and developed nations as a cause of cirrhosis, and, in some cases, of fulminant hepatic failure. Clinical manifestations of this infection, including evidence of hepatocellular liver injury, are mostly indistinguishable from alternative diagnoses.

Hepatitis E virus (HEV) is a globally important pathogen of acute and chronic hepatitis in humans. The HEV ORF1 gene encodes a nonstructural polyprotein, essential for RNA replication and virus infectivity. Expression and processing of ORF1 polyprotein are shown in prokaryotic and eukaryotic systems, however, its proteolysis into individual proteins is still debated. While molecular or biochemical characterization of methyltransferase, protease, hypervariable region, helicase and RNA polymerase domains in ORF1 has been achieved, the role of the X and Y domains in the HEV life cycle has only been demonstrated very recently. Clinically, detection of a number of ORF1 mutants in infected patients is implicated in disease severity, mortality and drug nonresponse. Moreover, several artificial lethal mutations in ORF1 offer a potential basis for developing live-attenuated vaccines for HEV. This article intends to present the molecular and clinical updates on the HEV ORF1 polyprotein.

Background: The Hepatitis E virus (HEV) has been responsible for major outbreaks in the developing countries affecting millions of people and acute sporadic hepatitis worldwide. The HEV methyltransferase is important for capping the 5'-end of the viral pregenomic RNA which is critical for viral infection., Objectives: We aimed to assess the substitutional profile in the HEV methyltransferase region in patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North Indian population and associate the substitutions with the poor outcome of the disease., Study Design: HEV RNA was detected and partial region encoding the Methyltransferase domain in the HEV genome was amplified by Reverse Transcriptase(RT-PCR). Viral load of HEV was quantified utilizing Real time PCR.32 representative samples consisting of 16 AVH and 16 ALF were directly sequenced and amino acid changes were compared using Fischer's exact (two-tailed) test., Results: Novel mutations Valine27Alanine (V27A), Aspartate29Asparagine (D29N) and Histidine105Arginine (H105R) mutation corresponding to 107T>C, 115G>A and 341 A>G substitutions respectively were significantly (p<0.0001) obtained in 16/16(100%) ALF patients compared to none (0/16) of the AVH patients. HEV viral load and disease severity parameters corresponding to the samples with D29N and V27A mutations were significantly higher compared to the isolates lacking these mutations while the H105R mutation was associated with decreased viremia., Conclusion: The D29N and V27A mutations had significant association with the poor outcome in ALF patients suggesting key role in enhancing HEV replication while the association of H105R mutation with decreased viremia creates interest on its antiviral aspects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aim: Hepatitis E virus (HEV) is a global disease and an important cause of acute liver failure (ALF) in the Indian subcontinent. The aim of this study was to assess the differences in the course of HEV-ALF as compared to other etiologies of ALF., Methods: We compared the clinical course, complications, and outcomes of HEV-ALF with other etiologies. We assessed the prognostic factors and compared existing prognostic scores in HEV-ALF patients., Results: One thousand four hundred and sixty-two ALF patients were evaluated between January 1986 and December 2015. HEV was the etiology of ALF in 419 (28.7%) cases, whereas non-A non-E hepatitis, HBV and anti-tuberculosis therapy (ATT) were the etiologies in 527 (36.0%), 128 (8.8%), and 103 (7.0%) cases, respectively. The frequency of cerebral edema in HEV-ALF (41.3%) was lower than that in non-A non-E ALF (52.9%; P < 0.001) and HBV-ALF (52.8%; P = 0.024). Infection and seizures were significantly less in patients with HEV-ALF compared to non-A non-E and HBV-ALF (P = 0.038 and 0.022, respectively). The survival of HEV-ALF patients was significantly better (55.1%, P < 0.001) than patients of other etiologies-including ATT (30.0%), non-A non-E (38.1%) and HBV (35.9%). In HEV-ALF patients, age, female sex, cerebral edema, prothrombin time >60 s, infection, and total bilirubin were observed as independent predictors of outcome on multivariate logistic regression analysis. Model for end-stage liver disease, acute liver failure study group model and King's College Hospital criteria had poor discriminative accuracy for outcome (area under receiver operator characteristic curve 0.63-0.64) in HEV-ALF., Conclusions: Hepatitis E virus-associated ALF has a better outcome than ALF of other etiologies.

Hepatitis E virus (HEV) infection among pregnant women is severe, often leading to fulminant hepatic failure and death, with mortality rates up to 15-25%. Studies suggest that differences in genotypes/subgenotypes, hormonal and immunological changes during pregnancy may contribute to the severe consequences for pregnant women with HEV. Although the increased mortality among pregnant women predominantly is seen in developing countries where genotype 1 is endemic, there are also large differences in mortality among pregnant women within these countries. The reason for this is not clear.

Few studies have reported sporadic hepatitis E virus (HEV) infections during non-outbreak periods in Africa. In this study, the prevalence of HEV infection in Sudan was investigated in 432 patients with acute hepatitis from 12 localities in North Kordofan, and from 152 patients involved in smaller outbreaks of hepatitis in the neighbouring Darfur. HEV infection was diagnosed in 147 (25%) patients: 98 from Kordofan and 49 from Darfur. The mortality was 10%; six of the patients who died from the infection were pregnant women. HEV RNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) in 38 (26%) patients: 22 from Kordofan and 16 from Darfur. Partial open reading frame (ORF) 1 and ORF2 were sequenced from HEV from nine and three patients, respectively. Phylogenetic analysis showed that the Sudanese strains belonged to genotype 1 (HEV1), and confirmed the segregation of African HEV1 strains into one branch divergent from Asian HEV1. It also revealed that the Sudanese strains from this study and from an outbreak in 2004 formed a separate clade with a common ancestor, distinct from strains from the neighbouring Chad and Egypt. This HEV strain has thus spread in a large area of Sudan, where it has caused both sporadic hepatitis E and outbreaks from at least 2004 and onwards. These data demonstrate that hepatitis E is a constant, on-going public health problem in Sudan and that there is a need for hepatitis E surveillance, outbreak preparedness, and general improvements of the sanitation in these remote areas of the country., Competing Interests: The authors declare no conflict of interest.

It is of great concern that pregnant women with acute viral hepatitis (AVH) type E have serious consequences. This study aimed to estimate the case-fatality risk (CFR) and potential risk factors of pregnant women with AVH type E. We searched the PubMed, EMBASE, and Web of Science databases for studies containing data on CFR in pregnancy with AVH type E. A pooled estimate of CFR was calculated using a random-effects model. Potential sources of heterogeneity were explored using subgroup analysis, sensitivity analysis, and meta-regression. We identified 47 eligible studies with a total African and Asian population of 3968 individuals. The pooled CFRs of maternal and fetal outcomes were 20·8% [95% confidence interval (CI) 16·6-25·3] and 34·2% (95% CI 26·0-43·0), respectively. Compared with these, the pooled CFR was highest (61·2%) in women with fulminant hepatic failure (FHF). Community-based surveys had lower pooled CFR (12·2%, 95% CI 9·2-15·6) and heterogeneity (25·8%, 95% CI 20·1-32·0) than hospital-based surveys. Univariate analysis showed that hospital-based surveying (P = 0·007), and patients in the third trimester of pregnancy or with FHF (P < 0·05), were significantly associated with CFR. Intrauterine fetal mortality (27·0%) was statistically higher than neonatal mortality (3·9%). Control measures for HEV infection would reduce feto-maternal mortality in Asia and Africa.

Hepatitis E virus is a common hepatotropic virus that causes serious gastrointestinal symptoms. Data of reported HEV cases in Zhejiang Province was collected between 2007 and 2012. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of hepatitis E infection. In this study, the average morbidity of hepatitis E infection was 4.03 per 100,000 in Zhejiang Province, peaking in winter and spring. The ratio between the male and the female was 2.39:1, and the high-risk population was found to be aged between 40 and 60. Trend surface analysis and IDW maps revealed higher incidences in the northwestern counties. The spatial-temporal analysis showed comparable incidences in the counties at the basins of three rivers, mostly under administration of Hangzhou Municipality. Besides, the seasonal exponential smoothing method was determined as the better model for the retrieved data. The epidemiological characteristics of HEV suggested the need of strengthened supervision and surveillance of sanitary water, sewage treatment and food in high-risk areas especially around the Spring Festival. Additionally, time series model could be useful for forecasting the epidemics of HEV in future. All these findings may contribute to the prevention and control of HEV epidemics.

Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status.

Background & Aims: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy., Methods: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA., Results: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed., Conclusions: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatitis E virus (HEV) infection is a worldwide disease. It is the first cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 56 000 deaths. In developing countries, hepatitis E is a waterborne infection. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects with a significant mortality rate in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. HEV can cause neurological disorders and in immunocompromised patients, chronic infections. The progression of acute hepatitis E is most often mild and resolves spontaneously. Diagnostic tools include anti-HEV IgM antibodies in serum and/or viral RNA in the blood or stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Question: Many of my patients are from Southeast Asia where hepatitis E virus (HEV) infection is quite common. What precautions can I suggest they take before traveling to these areas and what is the risk of contracting HEV during pregnancy?, Answer: Hepatitis E is a water-borne pathogen transmitted by the fecal-oral route. To reduce the risk of contracting HEV while traveling to endemic areas, it is important to maintain hygienic practices such as hand washing with safe water, particularly before handling food, avoiding drinking water or using ice cubes of unknown purity, and avoiding eating unpeeled fruits and vegetables. Currently there is no vaccine available in Canada for HEV. Hepatitis E infection during pregnancy, especially in the third trimester, is characterized by a more severe infection that sometimes results in fulminant hepatitis, increasing maternal and fetal mortality and morbidity., (Copyright© the College of Family Physicians of Canada.)

Acute viral hepatitis is the most common cause of jaundice in pregnancy. Amongst hepatitis E bears a deadly combination with pregnancy, leading to loss of very young lives. There is almost no data available in this aspect documenting prevalence, profile and effect of jaundice on outcome of pregnancy in Bangladesh. This observational study was done to determine and analyze the frequency, cause and outcome of jaundice in pregnancy among the admitted patients in the feto-maternal medicine wing of Bangabandhu Sheikh Mujib Medical University, for a 2 years period from August 2009 to July 2011. Management was done in collaboration with the hepatologists, hematologists and intensive care unit specialist. Outcome was noted in terms of the mode of delivery, maternal complications, need of blood transfusion and fresh frozen plasma and maternal end result. Fetal outcome was assessed by birth weight, Apgar score, neonatal admission, and perinatal mortality. Prevalence of jaundice was found 2.5% among all high risk and 1.3% among all obstetric admissions. Hepatitis E was the commonest cause and responsible for 80.4% cases of jaundice and next was cholestatic jaundice. Almost half of the patients (43.4%) faced complications like post partum haemorrhage (15.3%), hepatic encephalopathy (10.8%), ante partum hemorrhage (6.5%). Preterm delivery was noted in 71.1% cases. Out of 46 patients with jaundice four (4) mothers died due to hepatic encephalopathy in hepatitis E group. Regarding perinatal outcome 55.8% were of low birth weight, 35.3% had low Apgar score and perinatal mortality was 6.4%.

Objective: To observe the clinical spectrum, complications and pregnancy outcome in women with Hepatitis E., Methods: The descriptive prospective study was conducted at the Liaquat University of Medical and Health Sciences, Jamshoro, Red Crescent General Hospital and Saint Elizabeth Hospital, Hyderabad, from January 1, 2011, to December 31, 2013. All pregnant women with Hepatitis E positive on virology screening were included. The subjects were enrolled from the out-patient department as well as from among those admitted in either Obstetrics or Medical wards. Data was obtained through a predesigned proforma, and analysed using SPSS 20., Results: The overall mean age of the 45 women in the study was 27.78±6.742. There were 21(46.7%) women in 21-30 years age group, 22(48.9) were multiparous, 31(68.9%) were uneducated, and 29(64.4%) were from poor social class. Besides, late second trimester and third trimester of pregnancy was found in 27(60%), unstable condition 10(22.22%), disturbed liver function test 24(53.3%) and raised serum glutamic pyruvic transaminase level >101u/l 27(60%), deranged coagulation profile such as raised prothrombin time 25(55.5%), and activated partial thromboplastin time 18(40%)cases. Overall 36(80%) women were discharged, while 9 (20%) died. Besides, 10(24.4%) babies needed intensive care, 13(42.2%) foetuses died during intrauterine life, 5(11%) were stillborn, while 17(37.8%) were alive and were discharged home., Conclusions: Pregnant women with Hepatitis E were more vulnerable as their life, health and foetal outcome suffered a lot.

Background and Aims: The outcome of Hepatitis during pregnancy has been observed to be widely different by various authors, ranging from the benign to fatal. A poor outcome has increasingly been observed in pregnant women suffering from Hepatitis in Central India. Hence, this study was undertaken to study the incidence, causative organisms and chief prognostic factors affecting the outcome of viral hepatitis in pregnant women., Methods: Sixty-eight pregnant women reporting to the hospital with jaundice were enrolled as cases and their Haematological, Biochemical and Viral profiles were studied. Sixteen non- pregnant women were enrolled as controls and a similar workup was done. A comparison was done between the two groups We also divided the cases into two groups--survivors and non- survivors and tried to find out the factors predicting mortality. The unpaired student t test and chi square test were used to find out whether the differences were statistically significant., Results: Viral Hepatitis in pregnancy caused a very high maternal mortality (19.1%) and foetal wastage (42.6%). Hepatitis E virus was the commonest causative organism (77.9%) responsible for viral hepatitis during pregnancy. It also caused the highest maternal mortality due to fulminant hepatic failure. Maternal mortality was significantly higher in those women presenting with features of encephalopathy, SIRS, high bilirubin levels and prolonged prothrombin time. Vertical transmission was noted in Hepatitis B and E., Conclusions: Hepatitis E is the chief causative organism causing fulminant hepatic failure in pregnant women in Central India. It lead to very high rates of maternal mortality and foetal wastage.

We analyzed blood samples collected from 15 patients with chronic hepatitis E who were recipients of solid-organ transplants. All patients cleared the hepatitis E virus (HEV) except for 2 (nonresponders); 1 patient died. A G1634R mutation in viral polymerase was detected in the HEV RNA of the nonresponders; this mutation did not provide the virus with resistance to ribavirin in vitro. However, the mutant form of a subgenomic replicon of genotype 3 HEV replicated more efficiently in vitro than HEV without this mutation, and the same was true for infectious virus, including in competition assays. Similar results were obtained for genotype 1 HEV. The G1634R mutation therefore appears to increase the replicative capacity of HEV in the human liver and hence reduce the efficacy of ribavirin., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis E virus (HEV) causes outbreaks of jaundice associated with maternal mortality. Four deaths among pregnant women with jaundice occurred in an urban community near Dhaka, Bangladesh, in late 2008 and were reported to authorities in January 2009. We investigated the etiology and risk factors for jaundice and death., Methods: Field workers identified suspected cases, defined as acute onset of yellow eyes or skin, through house-to-house visits. A subset of persons with suspected HEV was tested for immunoglobulin M (IgM) antibodies to HEV to confirm infection. We used logistic regression analysis to identify risk factors for HEV disease and for death. We estimated the increased risk of perinatal mortality associated with jaundice during pregnancy., Results: We identified 4751 suspected HEV cases during August 2008-January 2009, including 17 deaths. IgM antibodies to HEV were identified in 56 of 73 (77%) case-patients tested who were neighbors of the case-patients who died. HEV disease was significantly associated with drinking municipally supplied water. Death among persons with HEV disease was significantly associated with being female and taking paracetamol (acetaminophen). Among women who were pregnant, miscarriage and perinatal mortality was 2.7 times higher (95% confidence interval, 1.2-6.1) in pregnancies complicated by jaundice., Conclusions: This outbreak of HEV was likely caused by sewage contamination of the municipal water system. Longer-term efforts to improve access to safe water and license HEV vaccines are needed. However, securing resources and support for intervention will rely on convincing data about the endemic burden of HEV disease, particularly its role in maternal and perinatal mortality., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Acute hepatitis E virus (HEV) infection has recently become the commonest cause of acute viral hepatitis in Hong Kong (HK) with majority of HEV belonging to genotype 4. Studies from China have shown that acute hepatitis E patients with underlying chronic hepatitis B virus (HBV) infection may have a worse outcome than those without. In India where genotype 1 is more prevalent, superinfection with hepatitis E on patients with chronic liver disease including chronic hepatitis B infection can cause liver decompensation., Objectives: The study aims to determine the clinical outcome of acute hepatitis E infection in patients with and without chronic hepatitis B infection in HK., Study Design: The rates of liver failure, liver-related mortality and all-cause mortality will be compared between acute hepatitis E patients with and without chronic hepatitis B. Analysis was performed using the Statistical Package for the Social Science (SPSS version 12.0). All statistical tests were two-sided, and statistical significance was taken as p<0.05., Results: Chronic HBV carriers with acute HEV infection were found to have higher liver failure rate, liver-related mortality and all-cause mortality, but the results did not reach statistical significance. Chronic HBV carriers were found to have statistically significantly lower admission ALT level, lower day 28 serum albumin level and higher day 28 serum ALT level., Conclusions: A prospective study with sufficient sample size is needed to confirm whether the clinical outcome of patients with chronic HBV infection is worse compared with patients who were not chronic HBV carriers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aim: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E., Methods: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the χ(2) test or Fisher's exact test for categorical variables and the Student's t test for continuous variables. A P value < 0.05 was considered statistically significant., Results: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure., Conclusion: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

During 4 months (November 2010-March 2011) of an outbreak of hepatitis E virus (HEV), 39 pregnant women presented at Port Sudan Hospital, Sudan, with various symptoms of viral hepatitis. The diagnosis of viral hepatitis was confirmed by serology using ELISA anti-HEV IgG and IgM. The mean (SD) maternal age and gestational age were 24·0 (4·2) years and 33·6 (3·7) weeks, respectively. Eight (20·5%) women were primigravidae. There were 11 (28·2%) maternal deaths, 14 (36·0%) intrauterine fetal deaths, and eight (20·5%) cases of postpartum haemorrhage. There were nine (23·0%) cases of preterm (<37 weeks of gestation) deliveries. Fulminant hepatitis with hepatic encephalopathy was the most common cause of death among these patients. Nine of these women died before delivery and the other two died immediately following the delivery due to severe haemorrhage. There were no significant differences in clinical and biochemical data between the women who died (11) and those who survived.

Objectives: We estimated the population-based incidence of maternal and neonatal mortality associated with hepatitis E virus (HEV) in Bangladesh., Methods: We analyzed verbal autopsy data from 4 population-based studies in Bangladesh to calculate the maternal and neonatal mortality ratios associated with jaundice during pregnancy. We then reviewed the published literature to estimate the proportion of maternal deaths associated with liver disease during pregnancy that were the result of HEV in hospitals., Results: We found that 19% to 25% of all maternal deaths and 7% to 13% of all neonatal deaths in Bangladesh were associated with jaundice in pregnant women. In the published literature, 58% of deaths in pregnant women with acute liver disease in hospitals were associated with HEV., Conclusions: Jaundice is frequently associated with maternal and neonatal deaths in Bangladesh, and the published literature suggests that HEV may cause many of these deaths. HEV is preventable, and studies to estimate the burden of HEV in endemic countries are urgently needed.

An acute infection with hepatitis E virus (HEV) genotype 3 subtype c was diagnosed in a patient with chronic lymphatic B-cell leukemia 6 weeks after the infusion of donor lymphocytes. Despite intensive care the patient died 39 days after admission due to pericardial effusion that was related to acute liver failure. We suggest that diagnostic procedures for detection of HEV infection should be seriously considered for the immunocompromised patient with elevated liver enzymes in the absence of a travel history to HEV endemic countries.

Space-time clustering of people who fall acutely ill with jaundice, then slip into coma and death, is an alarming phenomenon, more markedly so when the victims are mostly or exclusively pregnant. Documentation of the peculiar, fatal predisposition of pregnant women during outbreaks of jaundice identifies hepatitis E and enables construction of its epidemic history. Between the last decade of the 18th century and the early decades of the 20th century, hepatitis E-like outbreaks were reported mainly from Western Europe and several of its colonies. During the latter half of the 20th century, reports of these epidemics, including those that became serologically confirmed as hepatitis E, emanated from, first, the eastern and southern Mediterranean littoral and, thereafter, Southern and Central Asia, Eastern Europe, and the rest of Africa. The dispersal has been accompanied by a trend towards more frequent and larger-scale occurrences. Epidemic and endemic hepatitis E still beset people inhabiting Asia and Africa, especially pregnant women and their fetuses and infants. Their relief necessitates not only accelerated access to potable water and sanitation but also vaccination against hepatitis E.

Objectives: A subset of children with chronic liver disease (CLD) decompensate following an acute insult; however, data for children are not readily available. The present study aims to characterize the clinical presentation, etiology, outcome, and determinants of short-term mortality in children with an acute hepatic insult superimposed over CLD., Patients and Methods: Children of acute on chronic liver disease (ACLD) were grouped as acute on chronic liver failure (ACLF) and non-ACLF. ACLF was defined as per the definition proposed by Asian Pacific Association for the Study of Liver. The acute insult, etiology of CLD, and clinical and laboratory parameters at admission along with 3-month outcome were assessed. Receiver operating curve (ROC) was plotted to measure the performance of pediatric end-stage liver disease (PELD) score in predicting the 3-month mortality., Results: Of the 36 children with ACLD (median age 9.5; range 3-15 years), 17 fulfilled ACLF criteria and 19 non-ACLF. CLD was diagnosed for the first time in 86% children during their presentation with a superimposed acute insult. Wilson disease and autoimmune liver disease were the most common underlying etiology. Acute insult was caused by hepatitis E virus (HEV) in 27 (75%) children and hepatitis A virus (HAV) in 10 (28%). The 3-month mortality of ACLF group was significantly higher than that of non-ACLF group (59% vs 11%, P = 0.001). PELD score of >25.5 predicted death, with a sensitivity of 100% and specificity of 83.3%., Conclusions: Superinfection with hepatotropic viruses on CLD in children manifests as ACLD: ACLF and non-ACLF. Hepatitis E virus is the most common superinfection in the population studied. The mortality in ACLF is 5 times higher than that in the non-ACLF group. PELD score is useful in differentiating likely survivors and nonsurvivors.

Background: Epidemiological investigations, detections and vaccines of hepatitis E (HE) have been paid a focus of attention in prior studies, while studies on clinical features and risk factors with a large number of sporadic HE patients are scarce., Results: Sporadic HE can occur throughout the year, with the highest incidence rate in the first quarter of a year, in central of China. Of the 210 patients, 85.2% were male, and the most common clinical symptoms were jaundice (85.7%), fatigue (70.5%) and anorexia (64.8%). Total bilirubin (TBil), blood urea nitrogen (BUN), and international normalized ratio (INR) were found as major risk factors for death of HE patients. There was an overall mortality of 10%, and the mortality in the cirrhotic and non-cirrhotic group was 25% and 6.47%, respectively. Moreover, hepatitis E virus (HEV) infected patients with liver cirrhosis had a higher mortality and incidence of complications., Conclusions: TBil, BUN, and INR are major risk factors of mortality for HE. Liver cirrhosis can aggravate HE, and lead to a higher mortality. HEV infection can cause decompensation in patients with cirrhosis, as evidenced by a worsening Child-Pugh score.

The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.

Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%-21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration-approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world.

Hepatitis E virus (HEV) is the most frequent pathogen of a fecal-oral transmitted hepatitis in humans in many developing countries. It is endemic in the Middle East, in India, in Southeast Asia, central Asia as well as in Central and South America. It can be predominantly found in young adults. The mortality rate comes up to 2% whereas in pregnant women death rate can reach about 25%. Until a few years ago, acute hepatitis E was thought to be rare in industrialized countries: most cases were found in persons with a corresponding travel history. However, after improvement of the diagnostic possibilities, an increasing number of autochthonous cases with acute hepatitis E have become evident. Besides, a relatively high seroprevalence of 1 to 5% in the population in industrialized countries is noticeable which is converse to the only sporadic occurrence of acute hepatitis E. As a reason for this an animal reservoir for HEV is being discussed. The first HEV recovering from an animal succeeded in 1997 from a pig in the USA. Genetic typing showed close relationship between the porcine HEVand human HEV types. This confirmed the suspicion on a zoonotic potential of HEV. Transmission experiments revealed that non-human primates were sensitive to the porcine HEV and pigs could be infected with human HEV. Besides, occupational groups with close contact to pigs evidently have an increased risk for HEV infections. In addition, reports of acute hepatitis E after the consumption of undercooked wild boar meat supported the zoonotic potential of HEV. In the domestic pig and wild boar population in several European countries the virus is ubiquitous. In Germany a high percentage of the wild boars was proven to be infected with HEV. In contrast, studies of HEV circulation in domestic pigs are still pending.