Chapter 91 : Hepatitis A and E Viruses

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Viral hepatitis is the general term for inflammatory disease of the liver caused by at least five different viruses, with hepatitis A, B, C, D, and E viruses having a definite association with acute viral hepatitis. Of these, only hepatitis A virus (HAV) and hepatitis E virus (HEV) are enterically transmitted, and both cause acute and generally self-limiting infections without significant long-term carrier status. While there are no serious long-term sequelae in patients who recover from hepatitis A or hepatitis E, both viruses are associated with significant risks of acute, fulminant hepatitis and liver failure, and chronic hepatitis E has been reported in immunosuppressed patients. Severe outcomes are most commonly seen in patients with acute hepatitis A who also have chronic hepatitis C or hepatitis B infection, and also in patients with acute hepatitis E during pregnancy, especially during the third trimester. In the absence of these cofactors, the diseases show a general trend towards greater severity with increasing age, with the majority of infections being subclinical in children; however, severe and fulminant hepatitis A and E infections can occur at any age. In many developed countries, HEV infection is rare and HAV infection rates have declined, making recognition and diagnosis more challenging. This chapter discusses recent advances in our understanding of HAV and HEV infections, including diagnostic testing and interpretation.

Citation: Anderson D, Counihan N. 2015. Hepatitis A and E Viruses, p 1584-1598. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch91
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Genome replication and proteins of HAV and HEV. (A) Both viruses have positive-strand RNA genomes of around 7,200 to 7,500 nt. HAV replication proceeds via transcription from the genome to give full-length negative- and then positive-strand RNA, which can either be assembled into the virus particle or be used to translate further copies of a single, giant polyprotein which is processed by viral protease to yield the replicative proteins and capsid proteins. Assembly of five copies of each of the three capsid proteins (VP0, VP3 and PX) into pentamers and then 12 pentamers into capsids is required to form the antigenic sites of the virus. (B) Details of HEV replication are unknown, but it most likely produces a full-length negative-strand RNA, then full-length positive-strand RNA (new viral genomes), as well as subgenomic mRNAs which are used to translate the ORF2 (capsid) and ORF3 proteins plus the ORF1 polyprotein which is cleaved at unknown sites to yield the replicative proteins. Cleavage of full-length PORF2 results in assembly of virus-like particles from the truncated product, but the size of the authentic viral capsid protein is unknown. Modified from with permission. doi:10.1128/9781555817381.ch91.f1

Citation: Anderson D, Counihan N. 2015. Hepatitis A and E Viruses, p 1584-1598. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch91
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Image of FIGURE 2

Export of HAV from hepatocytes. Polarized hepatocytes are organized in complex structures within the liver, with bile canaliculi representing grooves formed from the apical domains of adjacent hepatocytes (insert). Bile is secreted into the canaliculi via the apical membranes and then flows into the small intestine via a network of ducts. The basolateral surfaces of hepatocytes are in contact with the hepatic blood supply and underlying tissue. Following replication in hepatocytes, HAV is exported via basolateral membranes towards the blood supply (step 1, arrow). The virus is then transported back through the cell (step 2, arrow), possibly by transcytosis, to the apical surface and secreted into bile canaliculi. doi:10.1128/9781555817381.ch91.f2

Citation: Anderson D, Counihan N. 2015. Hepatitis A and E Viruses, p 1584-1598. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch91
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Image of FIGURE 3

Serological and virological courses of infection with HAV or HEV. High levels of HAV-specific IgG provide lifelong protection from reinfection, but HEV-specific IgG declines rapidly during the first 6 months and might not persist at protective levels for life. Modified from with permission. doi:10.1128/9781555817381.ch91.f3

Citation: Anderson D, Counihan N. 2015. Hepatitis A and E Viruses, p 1584-1598. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch91
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RPOC tests for HEV-specific IgM. Undiluted serum (25 μl) was added to the specimen window (a) and allowed to migrate through part of the membrane. Approximately 30 seconds later, 3 drops of buffer was added to the buffer window (b), the separator was removed by pulling the protruding end (c), and 1 drop of wash buffer was added to the specimen window. Results were visible through the viewing window (d) after 8 minutes. Samples are considered positive for IgM anti-HEV if two colored lines appear in the viewing window, and negative for IgM anti-HEV if a colored line appears only at the control line. Test kits as described ( ), kindly provided by MP Biomedical, Singapore. Data from the authors’ laboratory. doi:10.1128/9781555817381.ch91.f4

Citation: Anderson D, Counihan N. 2015. Hepatitis A and E Viruses, p 1584-1598. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch91
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