Chapter 53 : Hepatitis C Virus

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Hepatitis C virus (HCV), a member of the genus in the family, is a single-stranded RNA virus that infects humans and other higher primates and has a selective tropism to the liver. Although the HCV particle itself is difficult to demonstrate, by inferring from the virions of other , the putative particle is composed of a nucleocapsid composed of the core protein and viral RNA, surrounded by a phospholipid membrane in which the viral envelope proteins are embedded. The replication cycle of the HCV can be divided into stages: binding and entry into the cell; polyprotein translation and processing; RNA replication; and packaging, assembly, and release of the virion. The current recommendations for disinfecting reusable endoscopic equipment by mechanical washing with detergent and soaking in 2% glutaraldehyde were shown to be sufficient to eliminate contamination with HCV. Hepatitis C can be transmitted vertically from mother to child. Successful eradication of hepatitis C with antiviral treatment significantly reduces, but does not eliminate completely, the risk of chronic hepatitis C (CHC). Serologic assays for detecting HCV infection were rapidly developed and improved following the initial discovery of the virus because of the urgent need to screen blood donors and prevent transmission. In general, antiviral treatment is indicated for any adult patient with CHC who is viremic and has elevated aminotransferases or histologic evidence of progressive liver disease, i.e., fibrosis extending beyond the portal tracts.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53

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Major Histocompatibility Complex Class I
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Image of FIGURE 1

Phylogenetic analysis of complete open reading frame sequences demonstrating clustering to six genotypes and subgenotypes. The major epidemiological attributes of each genotype are noted. IDUs, injection drug users. (Reprinted from reference with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 2

Geographic distribution of HCV genotypes. Genotype 1 is the most prevalent and can be seen worldwide. Genotype 3 is more common in south and Southeast Asia; genotype 4 is seen almost exclusively in patients from central Africa, Egypt, and Saudi Arabia; genotype 5 is mostly confined to South Africa; and genotype 6 is confined to Southeast Asia. (Reprinted from reference with permission of Elsevier.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 3

Electron microscopy of viral particles. (a) Immunogold electron microscopy of a viral particle from patient serum. The sample was incubated with anti-E1 polyclonal antibody and a secondary antibody conjugated to colloidal gold particles. An inner core (arrow) seems to be included within the particle. (Reprinted from reference with permission.) (b) Negative-stain electron microscopy of HCV harvested from Huh7.5 cells infected in vitro with HCV strain JFH-1. Spherical particles of uniform size with inner cores can be seen.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 4

Genome structure of HCV. (a) The positive-sense single-stranded RNA genome of HCV has one long open reading frame containing genes for three structural and seven nonstructural proteins and flanked by two UTRs. (b) Sequence and secondary structure of the 5′ UTR. The AUG start codon for the open reading frame is highlighted in stem-loop IV. (c) Sequence and secondary structure of the 3′ UTR. Arrows indicate variable base pairs in the stem of stem-loop I, and the asterisk indicates the variable nucleotide in the loop of stem-loop I.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 5

Viral replication cycle. Binding of the virus to the cell surface and internalization (a) are followed by release of the viral RNA (b), harnessing of the cellular ribosomes, and protein translation and processing (c). The viral proteins, associated with the ER membrane, promote the formation of replication complexes anchored to lipid membranous webs (d) in which the RNA-dependent polymerase NS5B creates copies of the viral RNA through a negative-strand RNA intermediate. HCV RNA is then packaged into membrane-covered viral particles (e) and exported from the cell, presumably through the exocytosis pathway (f). (Reprinted from reference with permission of Macmillan Publishers Ltd.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 6

World distribution of HCV seroprevalence. The highest prevalence is in Egypt, 22%. Other countries with a high prevalence of infection include Mongolia, Bolivia, and several sub-Saharan nations. (Reprinted from ( ) with permission.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 7

Evolution of screening methods for donated blood and the corresponding decrease in transfusion-related hepatitis. Data are shown for non-A, non-B hepatitis before the availability of anti-HCV testing and for HCV afterwards. HBsAg, hepatitis B virus surface antigen; anti-HBc, hepatitis B virus core antibodies; NAT, nucleic acid technology. (Adapted from reference .)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 8

Histopathological findings in CHC. (a) Moderate inflammatory activity. The portal area is expanded by an inflammatory infiltrate and a lymphoid follicle (black arrow). The infiltrate disrupts the limiting plate between portal area and hepatic parenchyma (“interface hepatitis,” black arrowheads). Foci of lobular inflammation can also be seen (white arrowhead) as well as an acidophil body (white arrow). Hematoxylin and eosin stain; magnification, ×400. (b) HCV-associated steatosis. The inflammatory infiltrate (arrow) is accompanied by fat droplets in hepatocytes (arrowheads). Hematoxylin and eosin stain; magnification, ×138. (Images provided by David Kleiner, National Cancer Institute, Bethesda, MD.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 9

Immune response to HCV infection. HCV infection induces innate and adaptive immune responses. Induction of HCV-specific cytotoxic T cells by antigen-presenting cells is crucial in viral clearance and prevention of chronic infection, through both cytopathic and noncytopathic mechanisms. Antibodies against HCV, secreted by B cells, appear late and do not seem to have an important role in viral control. Activation of nonspecific inflammatory cells causes liver injury. Chronic stimulation of lymphoid cells can induce autoimmunity and lymphoproliferative disorders, including cryoglobulinemia and lymphoma. TH, T helper; Ig, immunoglobulin; CTL, cytotoxic T lymphocyte.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 10

Clinical course and natural history of HCV infection. (a) Acute, spontaneously resolving hepatitis C. The liver enzyme elevation, symptoms, and appearance of antibodies usually lag behind viremia. Seropositivity persists for years after recovery but may decline after decades. (b) Acute infection progressing to CHC. Viral levels and enzyme elevations are relatively stable in the chronic phase. Accumulation of fibrosis occurs gradually, over many years. The gray dashed line represents the upper limit of the norm for ALT. HCVAb, anti-HCV antibodies.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 11

Evolution of treatment regimens for CHC and corresponding rates of sustained virologic response. IFN, alfa interferon; PEG-IFN, pegylated alfa interferon; RBV, ribavirin.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Viral proteins and their function in the viral life cycle

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Tissue culture model systems

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Treatment of CHC

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
Generic image for table

Specifically targeted antiviral therapeutic agents against hepatitis C in clinical trials

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53

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