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© Borgis - Postępy Nauk Medycznych 11/2014, s. 761-765
*Maciej Bura, Arleta Kowala-Piaskowska, Iwona Mozer-Lisewska
Zapalenie wątroby typu E jako nowe nadchodzące wyzwanie związane z zakażeniem endemicznym
Hepatitis E as a novel approaching challenge of endemic infection
Chair and Department of Infectious Diseases, University of Medical Sciences, Poznań
Head of Chair: prof. Iwona Mozer-Lisewska, MD, PhD
Streszczenie
W artykule przedstawiono podstawowe dane dotyczące wirusa zapalenia wątroby typu E (HEV) oraz wywoływanej przez niego choroby. Tradycyjnie wirusowe zapalenie wątroby typu E (wzw E) postrzegane jest jako problem występujący w krajach rozwijających się, z gorącym klimatem i niedostatecznymi warunkami sanitarnymi. Ta postać ostrego wzw stanowi duże zagrożenie dla kobiet ciężarnych. W krajach rozwiniętych rozpoznawano chorobę u osób wracających z podróży do obszarów endemicznych. W ostatnich latach nasza wiedza o wirusie oraz wzw E została uzupełniona o istotne praktycznie dane.
W niniejszej pracy zwrócono uwagę na nowe informacje dotyczące zakażeń HEV: aktualną systematykę oraz różnorodność genetyczną wirusa, odnotowano jego występowanie w krajach uprzemysłowionych jako czynnika etiologicznego lokalnie nabytego wzw E oraz podano najważniejsze drogi przenoszenia. Wirus może indukować różne postaci kliniczne zakażenia (w tym proces przewlekły oraz manifestacje pozawątrobowe). Wymieniono populacje pacjentów szczególnie podatne na nabycie zakażenia, zasady rozpoznawania zapalenia wątroby typu E oraz potencjalne możliwości terapeutyczne tej choroby, na razie tylko w wyjątkowych przypadkach. Warto zauważyć pojawienie się możliwości skutecznej profilaktyki czynnej choroby za pomocą szczepień z zastosowaniem rekombinowanego antygenu (na razie tylko w Chinach).
Podstawą do rozpoznania zakażenia HEV jest uwzględnianie go w diagnostyce różnicowej chorób przebiegających z żółtaczką i/lub niewyjaśnioną hiperaminotransferazemią.
Celem artykułu jest zwrócenie uwagi Czytelników na dyskutowany problem, co zaowocuje rozpoznaniem sytuacji dotyczącej zakażeń HEV w Polsce.
Summary
The paper presents basic data on the hepatitis E virus (HEV) and the disease caused by it. Traditionally, hepatitis E is regarded as a problem found in developing countries with hot climates and poor sanitation. Acute hepatitis E poses a high risk to pregnant women. In developed countries, hepatitis E has been diagnosed in people returning from trips to endemic areas. In recent years our knowledge on HEV and hepatitis E has been updated with important practical information.
In this paper attention is drawn to new information on HEV infections: current classification and the genetic diversity of the virus, reports on its presence in industrialized countries as an aetiological factor of locally acquired hepatitis E and the most important routes of infection with the virus. HEV can induce various clinical types of infection, including chronic disease and non-hepatic manifestations. Populations of patients particularly prone to contracting the infection, diagnostic methods for hepatitis E and potential therapeutic options, so far available only in special cases, are presented. Interestingly, a possibility has emerged to efficiently prevent the active disease through immunization with a recombinant antigen (so far only in China).
It is essential for the recognition of HEV infection to include it in the differential diagnosis of diseases with jaundice and/or unexplained hyperaminotransferasemia.
The aim of this paper is to draw the attention of readers to the discussed problem in order to achieve a more detailed insight into the status of HEV infections in Poland.



Introduction
In his classical system of viral hepatitis, MacCallum distinguished two types of the disease: serum hepatitis and infectious hepatitis (1). In subsequent decades, several primary hepatotropic viruses were identified, which helped to extend MacCallum’s classification, following its basic structure, where the major transmission route for infection was the key criterion for classification. According to the extended system, the group of enterically transmitted viruses (mainly via the faecal-oral route) includes hepatitis A and E viruses (HAV and HEV), while the parenterally transmitted viruses include hepatitis B, C and D viruses (HBV, HCV and HDV).
HEV identification was associated with the epidemics of hepatitis of unknown aetiology which occurred among Soviet soldiers stationed in Afghanistan in the 1980s (2). One of the researchers ingested a faecal extract derived from patients. The researcher contracted the disease, and an electron microscope examination of his stools revealed the presence of spheroid virus-like particles of 27 to 30 nm in diameter. The particles reacted with sera from the patients and serum from the researcher taken a few weeks after the infection occurred. It was possible that the new infectious factor was transmitted to other primates (crab-eating macaque, Macaca fascicularis), causing similar symptoms in them. The HEV genome was described at the beginning of the following decade (3, 4).
The virus
The first virology analyses suggested that this previously unidentified aetiological factor of enterically transmitted non-A, non-B hepatitis was similar to viruses from the Caliciviridae family and for this reason HEV was classified to this group for a certain time. However, because of significant differences in the organisation of the genome, the virus was finally classified to a separate family, Hepeviridae (genus Hepevirus) (5).
HEV is a small (27-34 nm), spheroid, non-enveloped virus, with icosahedral symmetry, containing a single-strand positive-sense RNA that is approximately 7200 bases in length. The genome is organized in three open reading frames (ORF1-3), limited from both ends (5’ and 3’) with non-coding regions. The product of ORF1 is a large non-structural polyprotein whose components play a key role in virus replication (e.g. RNA-dependent RNA polymerase activity) (6). ORF2 encodes the structural protein of the viral capsid, which contains epitopes inducing the formation of neutralizing antibodies (6). Numerous antigens originating from ORF2 are basic design elements for various serological assays used in the diagnostics of HEV infection. In addition, recombined products of this region have been used for the production of preventive vaccines. The ORF3 derivative is a small-size phosphoprotein linked with the cytoskeleton and the HEV capsid protein (6). It is thought to optimize the conditions in the host cell by facilitating virus replication, inhibiting the mechanisms of natural immune response, and taking part in the process of HEV leaving the infected cell. ORF3 protein is the key substance determining the in vivo infectivity of HEV. HEV replicates in the cytoplasm of the infected host cells.
Although the heterogeneity of HEV strains able to cause the disease in humans is significant (4 genotypes and at least 24 subtypes) (7), all variants represent one serotype of the virus (8). Genotypes 1 and 2 cause infections only in humans and primates, while infections caused by genotypes 3 and 4 also affect certain species of other mammals (domestic swine, wild boar, deer), which can be a source of zoonotic diseases transmitted to humans (9). Anti-HEV and/or HEV-RNA antibodies were found in a wider range of animals (chickens, rabbits, rats, mongooses, ferrets, dogs, cats, goats, cattle, horses and sheep), but it is not known whether this fact has any practical role in the aspect of human disease (10, 11).
Epidemiology of HEV infections
The genetic diversity of HEV has important practical implications because individual genotypes are characterized by different geographical coverage and a number of epidemiological particulars. In addition, there are differences in the clinical course of individual variants of the viral infections in humans. The strains belonging to genotype 1 are present in the developing countries of Asia and Africa, genotype 2 was found in Mexico, Chad and Nigeria, but genotype 3 has the widest distribution, occurring throughout the world (except Africa). Finally, genotype 4 is found mainly in Asia, but a small number of cases have also been reported from Western Europe (7, 12, 13).
Highly endemic areas

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otrzymano: 2014-09-10
zaakceptowano do druku: 2014-10-14

Adres do korespondencji:
*Maciej Bura
Chair and Department of Infectious Diseases University of Medical Sciences
ul. Szwajcarska 3, 61-285 Poznań
tel. +48 618-739-376
ola_kielb@wp.pl

Postępy Nauk Medycznych 11/2014
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