Chapter 88 : Hepatitis A and E Viruses

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The 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. Acute infections with any of the hepatitis viruses cannot be distinguished on clinical characteristics or pathological examinations, and the diseases caused by HAV and HEV are considered together. Clinical presentation of acute viral hepatitis commonly begins with nonspecific, "flu-like" symptoms such as fever, headache, anorexia, nausea, and abdominal discomfort. The high proportion of window period cases found in this study contrasts with the high sensitivity of HAV IgM detection in other studies and may be related to high-dose infections with short incubation periods, and/ or early case detection due to active surveillance of the outbreak. The authors also reported the detection of HAV RNA in 26% of patients initially classified as having acute, sporadic non-A, non-C hepatitis. The detection of HEV-specific IgM should therefore become the method of choice for diagnosis of acute HEV infection in areas of low prevalence. Early assays for HEV-specific IgM showed false-positive reactivity in 3% of U.S. blood donors, roughly equivalent to the rate of IgG reactivity, which limited their usefulness in areas where HEV is nonendemic.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
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Image of FIGURE 1

Genome replication and proteins of HAV and HEV. Both viruses have positivestrand RNA genomes of around 7,200 to 7,500 nt. (A) HAV replication proceeds via transcription from the genome to give full-length negative-strand RNA and then positive-strand RNA, which can either be assembled into the virus particle or 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 and 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, as well as 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 reference , with permission.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
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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 (inset). 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.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
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Image of FIGURE 3

Serologic and virologic courses of infection with HAV or HEV. For HAV, the serologic responses shown are typical of those detected with numerous commercially available assays. For HEV, the serologic responses shown are those that probably occur in most patients, but the detection of these responses will vary widely depending on the assays used. 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 reference with permission.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
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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 s later, 3 drops of buffer were 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 min. 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 are as described previously ( ), kindly provided by MP Biomedicals. Data are from our laboratory.

Citation: Anderson D, Counihan N. 2011. Hepatitis A and E Viruses , p 1423-1436. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch88
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