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Chapter 83 : Viral Hepatitis

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Abstract:

The more recently introduced molecular tests that detect and quantify viral genomes complement the information obtained immunologically and, due to rapid turnaround times and the availability of user-friendly commercial kits, have acquired a key position in both the diagnosis and the follow-up of viral hepatitis. Direct detection of the infectious agent has an ancillary role in the laboratory diagnosis of hepatitis A due to the reliability and ease of anti-hepatitis A virus (HAV) immunoglobulin M (IgM) testing. Viral RNA is tested for mainly by reverse transcriptase PCR (RT-PCR). Certainly more important for laboratory diagnosis and disease management, however, are the so-called hepatitis B e antigen (HBeAg)-minus core or precore mutants of the virus, which are unable to express HBeAg due to a stop codon in the C gene, and the drug-resistant variants that are commonly found in patients undergoing therapy. Qualitative nucleic acid-based tests are most useful in assessing the safety of blood donations but prove useful also when a suspicion of active infection based on serological grounds needs to be confirmed. In this case, it is advisable to retest negative patients several times at intervals of several weeks in order to identify the ones who might have intermittent viremia, as is frequently observed in the course of spontaneous resolution or antiviral therapy.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83

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Figures

Image of FIGURE 1
FIGURE 1

Typical course of immunovirological events and manifestations of liver damage in symptomatic infection by the enterically transmitted HAV (top) and HEV (bottom). Both viruses produce many more inapparent than symptomatic infections, but the immunovirological events are similar to the ones depicted. Neither virus produces chronic infections.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 2
FIGURE 2

Algorithm for use and interpretation of laboratory tests for HAV infection. HAV RNA detection is usually carried out with stool samples.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 3
FIGURE 3

Typical course of immunovirological events and manifestations of liver damage in symptomatic acute, self-limiting, and chronic HBV infection. The proportion of infections that chronicize is indicated as 15% but in fact varies widely, depending on the patient’s age and other variables (see text). The initial, acute phases are essentially the same, regardless of whether the infection resolves or becomes chronic. The vast majority of HBV infections do not produce overt disease or do so after many years of persistence; however, the immunovirological events are similar to the ones depicted.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 4
FIGURE 4

Algorithm for use and interpretation of laboratory tests for HBV infection. See also Table 3 .

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 5
FIGURE 5

Typical course of immunovirological events and manifestations of liver damage in symptomatic, acute self-limiting and chronic HCV infection. The initial, acute phases are essentially the same, regardless of whether infection resolves or becomes chronic. HCV has a greater tendency to persist than HBV. The vast majority of both acute and chronic infections do not produce overt disease or do so after many years of persistence; however, the immunovirological events are similar to the ones depicted.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 6
FIGURE 6

Algorithm for use and interpretation of laboratory tests for HCV infection. Under selected circumstances, HCV-Ag detection and measurement can be used in place of HCV RNA detection. Immunoblotting as a means to confirm positive EIA results is currently skipped by many laboratories, which proceed directly to HCV RNA detection and use confirmation by immunoblotting only for the patients who test HCV RNA negative.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 7
FIGURE 7

Typical course of immunovirological events and manifestations of liver damage in symptomatic HDV infection. In concomitant infection (coinfection) of naive individuals with HBV and HDV, HBV markers are affected very little by concurrent HDV replication, and HDV markers may escape detection due to their transient nature. In superinfection of individuals already infected with HBV, HDV replication is particularly florid and may produce transient reductions or unde-tectability of HBV DNA and HBsAg (see text).

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 8
FIGURE 8

Algorithm for use and interpretation of laboratory tests for HDV infection. A prerequisite for HDV testing is that the patient is infected with HBV. In regions of high HDV endemicity, HDV testing should be carried out every second or third year or whenever there is an unexplained aggravation of hepatitis. In regions of low endemicity, HDV testing should essentially be limited to IDUs or people returning from areas of endemicity.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Image of FIGURE 9
FIGURE 9

Algorithm for use and interpretation of laboratory tests for HEV infection. HEV RNA assays should be performed only when there are solid reasons for suspecting HEV infection (see text), on stool samples collected within 2 to 3 weeks from clinical onset.

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
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Tables

Generic image for table
TABLE 1

Viruses discussed in this chapter

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
Generic image for table
TABLE 2

Serum parameters useful for the biochemical evaluation of liver necrosis and function

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83
Generic image for table
TABLE 3

Interpretation of immunovirological profiles for HBV

Citation: Bendinelli M, Pistello M, Freer G, Vatteroni M, Maggi F. 2006. Viral Hepatitis, p 724-745. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch83

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