Hepatitis E virus (HEV) seroprevalences of 0.3%-53% were reported from industrialized countries. Because these estimates may be influenced by detection assays, this study compares 3 frequently used tests for HEV detection: the MP Diagnostics HEV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), the Axiom Diagnostics HEV IgG enzyme immunoassay (EIA), and the Mikrogen recomLine HEV IgG assay. Sera from 200 healthy healthcare workers and 30 individuals with acute HEV infection were analyzed. Among the healthy individuals, HEV IgG was found in 4.5% by the MP Diagnostics assay, in 29.5% by the Axiom Diagnostics assay, and in 18% by the Mikrogen assay. Among individuals with acute HEV infection, positive results were obtained for 83.3%, 100%, and 96.7%, respectively. Thus, the 3 assays show clear differences in diagnostic sensitivity.

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Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current view of the global circulation and epidemiology of this emerging virus. The history of HEV, from the first reported enteric non-A non-B hepatitis outbreaks, to the discovery of the viral agent and the molecular characterization of the different human pathogenic genotypes, is discussed. Furthermore, the current state of research regarding the virology of HEV is critically assessed, and the challenges towards prevention and diagnosis, as well as clinical risks of the disease described. Together, these points aim to underline the significant impact of hepatitis E on global health and the need for further in-depth research to better understand the pathophysiology and its role in the complex disease manifestations of HEV infection.

A steep rise in Hepatitis E diagnoses is currently being observed in Germany and other European countries. The objective of this study was (i) to assess whether this trend mirrors an increase in infection pressure or is caused by increased attention and testing and (ii) estimate individual and population-based Hepatitis E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured anti-HEV IgG prevalence in 10 407 adults participating in two linked, population-representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this period, we found a moderate but statistically significant decline of overall anti-HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence increased with age and peaked in persons born between 1935 and 1959 suggesting a past period of increased infection pressure. Paired samples of individuals participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and seroreversion rates of 6.2% and 22.6% among seronegative and seropositive individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions per year in the German population. While anti-HEV seroprevalence has decreased in the last decade, infection pressure and seroincidence remains high in Germany. Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to an increased awareness of clinicians and indicate that still there is a gap between incident and diagnosed cases. Studies on the true burden of the disease, specific risk factors and sources of autochthonous infections as well as targeted prevention measures are urgently needed.

The hepatitis E virus (HEV) is transmitted via the faecal–oral route in developing countries (genotypes 1 and 2) or through contaminated food and blood products worldwide (genotypes 3 and 4). In Europe, HEV subtypes 3c, 3e and 3f are predominant. HEV is the leading cause of acute hepatitis globally and immunocompromised patients are particularly at risk. Because of a lack of cell culture systems efficiently propagating wild-type viruses, research on HEV is mostly based on cell culture-adapted isolates carrying uncommon insertions in the hypervariable region (HVR). While optimizing the cell culture system using the cell culture-adapted HEV strain 47832c, we isolated three wild-type strains derived from clinical specimens representing the predominant spectrum of HEV in Europe. The novel isolates 14-16753 (3c), 14-22707 (3e) and 15-22016 (3f-like) replicate to high viral loads of 108, 109 and 106.5 HEV RNA copies/mL at 14 days post-inoculation, respectively. In addition, they could be kept as persistently infected cell cultures with constant high viral loads (~109 copies/mL) for more than a year. In contrast to the latest isolates 47832c, LBPR-0379 and Kernow-C1, the new isolates do not carry genome insertions in the HVR. Optimization of HEV cell culture identified amphotericin B, distinct salts and fetal calf serum (FCS) as important medium supplements. Overconfluent cell layers increased infectivity and virus production. PLC/PRF/5, HuH-7-Lunet BLR, A549 and HepG2/C3A supported replication with different efficiencies. The novel strains and optimized cell culture system may be useful for studies on the HEV life cycle, inactivation, specific drug and vaccine development.

In the past decade, an increasing frequency of acute hepatitis E was noted in Germany and other European countries. Moreover, a high prevalence (17%) of hepatitis E virus (HEV) immunoglobulin G antibodies (anti‐HEV) was recently found in the adult German population. Although this suggests an emerging pathogen, reports from other countries gave hints to a completely new aspect: a possible decrease in anti‐HEV prevalence during the last decades. To investigate the time trends of hepatitis E in southeastern Germany, we performed anti‐HEV testing in sera taken from adults in 1996 and 2011. Surplus serum specimens stored during routine operations of our diagnostic laboratory were used. The sample comprised two sets of 1,092 sera taken in 1996 and 2011, each with 182 specimens in six age groups from 20‐79 years. Testing was performed using an HEV IgG enzyme immunoassay (EIA, Axiom Diagnostics), and the recomLine HEV IgG immunoblot (Mikrogen). A significant difference in anti‐HEV prevalence was observed between the two groups: 50.7% of individuals tested positive in the 1996 group as compared to 34.3% in 2011 (EIA, P < 0.001). Results by immunoblot analysis were 20.5% (1996) versus 14.5% (2011), P < 0.001. Differences were found in all age groups and were more pronounced for the 20‐39‐year age group. Conclusion: The prevalence of anti‐HEV has decreased significantly in the past decades in southeastern Germany. The phenomenon of HEV being an emerging pathogen is thus most probably due to an increasing awareness of the disease. (Hepatology 2014;60:1180–1186)

The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV‐related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV‐1 to HEV‐8) with different human and animal hosts and other HEV‐related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food‐borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre‐existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain‐Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion‐transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion‐transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.

Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack of efficient cell culture systems hampers systematic studies on its replication cycle, virus neutralization and inactivation. Here, several cell lines were inoculated with the HEV genotype 3c strain 47832c, previously isolated from a chronically infected transplant patient. At 14 days after inoculation the highest HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells, whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus replication. Inoculation of A549-derived subclone cell lines resulted in most cases in reduced HEV replication. However, the subclone A549/D3 was susceptible to lower virus concentrations and resulted in higher virus yields as compared to parental A549 cells. Transcriptome analysis indicated a downregulation of genes for carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 5 and 6, and an upregulation of the syndecan 2 (SDC2) gene in A549/D3 cells compared to A549 cells. However, treatment of A549/D3 cells or A549 cells with CEACAM- or syndecan 2-specific antisera did not influence HEV replication. The results show that cells supporting more efficient HEV replication can be selected from the A549 cell line. The specific mechanisms responsible for the enhanced replication remain unknown.