Hepatitis E Virus

Abstract

The hepatitis E virus (HEV) infection is a worldwide disease. HEV is usually responsible of an acute self‐limiting infection, but pregnant women and patients with preexisting liver disease can suffer from severe forms. HEV infections can lead to chronic hepatitis and cirrhosis in immunocompromised patients. Extrahepatic manifestations can also occur. In developing countries, HEV is transmitted via contaminated water. In developed countries, transmission is zoonotic due to consumption of uncooked or undercooked infected meat and direct contact with infected animals. Transfusion‐transmitted HEV infections were also described. HEV infections are diagnosed by detecting anti‐HEV antibodies in the serum. In immunocompromised patients, detecting HEV RNA in the blood or faeces is needed. A 3‐month course of ribavirin is effective for treating chronic infection: a sustained virologic response occurs in 78% of patients. Vaccine has been recently licensed for use in China and provides protection against hepatitis E for up to 4.5 years.

Key Concepts

  • The hepatitis E virus infection is a worldwide disease.
  • Animal reservoir is responsible for autochthonous HEV infection in developed countries.
  • Chronic infections are possible in immunocompromised patients.
  • Treatment of choice for chronic HEV infections is a 3‐month course of ribavirin.
  • Vaccine afforded a sustained protection.

Keywords: hepatitis E virus; zoonosis; chronic hepatitis; diagnosis; treatment; prevention

Figure 1. Hepatitis E virus genome. The 5′ end of the RNA genome is capped with 7‐methylguanosine (7 mG), and the 3′ end is polyadenylated (poly A). ORF1 encodes the nonstructural proteins, including a methyl transferase (MT), cysteine protease (P), helicase (Hel) and RNA polymerase (RdRp), as well as three regions of unknown function (Y, PPR and X).
Figure 2. HEV lifecycle. HEV particles become bound to the proteoglycan heparan sulphate at the cell surface (1), interact with their unknown specific receptor (2) and are internalised in a clathrin‐dependent process (3). The virus uncoats (4). RNA is released and is translated into nonstructural proteins in the host cell cytoplasm (5). Virus polymerase replicates the positive‐sense (+) genomic RNA to form a negative‐sense (−) transcript (6). This RNA(−) serves as a template for the synthesis of full‐length positive‐sense transcripts (7) or a 2.2‐kb subgenomic RNA (8). The RNA(+) is translated into ORF2 (triangle) and ORF3 (circles) proteins (9). The ORF2 protein passes through the endoplasmic reticulum and packages the virus genomic RNA to assemble new virions (10). The ORF3 is also associated with the endomembrane and is probably implicated in virus egress (11). Mature virions are associated with ORF3 protein and lipids (12).
Figure 3. Worldwide distribution of the four major genotypes of HEV.
Figure 4. Course of an acute hepatitis E virus infection.
Figure 5. Diagnostic algorithm for acute hepatitis E.
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Further Reading

Aggarwal R (2013) Hepatitis E: clinical presentation in disease‐endemic areas and diagnosis. Seminars in Liver Disease 33 (1): 30–40.

van den Berg B, van der Eijk AA, Pas SD, et al. (2014) Guillain‐Barre syndrome associated with preceding hepatitis E virus infection. Neurology 82 (6): 491–497.

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Kamar N, Mansuy JM, Cointault O, et al. (2008) Hepatitis E virus‐related cirrhosis in kidney‐ and kidney‐pancreas‐transplant recipients. American Journal of Transplantation 8 (8): 1744–1748.

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Lhomme, Sebastien, Abravanel, Florence, Chapuy‐Regaud, Sabine, Dubois, Martine, Mansuy, Jean‐Michel, Peron, Jean‐Marie, Alric, Laurent, Rostaing, Lionel, Kamar, Nassim, and Izopet, Jacques(Sep 2015) Hepatitis E Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001030.pub3]