Hepatitis Type C
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p515-516
2025-11-30
67
Clinical and epidemiologic studies and cross-challenge experiments in chimpanzees in the past had suggested that there were several non-A, non-B (NANB) hepatitis agents that, based on serologic tests, were not related to HAV or HBV. The major agent was identified as HCV. HCV is a positive stranded RNA virus, classified as family Flaviviridae, genus Hepacivirus. Various viruses can be differentiated by RNA sequence analysis into at least six major genotypes (clades) and more than 100 subtypes. Clades differ from each other by 25–35% at the nucleotide level; subtypes differ from each other by 15–25%. The genome is 9.4 kb in size and encodes a core protein, two envelope glycoproteins, and several non structural proteins (Figure 1). The expression of cDNA clones of HCV in yeast led to the development of serologic tests for antibodies to HCV. Most cases of posttransfusion NANB hepatitis were caused by HCV.
Fig1. Genetic organization of the hepatitis C virus genome. The single open reading frame is expressed as a polyprotein that gets processed; the positions of structural and nonstructural domains are shown. HVR-1 represents the highly variable region of an envelope glycoprotein. (Redrawn with permission from Chung RT, Liang TJ: Hepatitis C virus and hepatocellular carcinoma. In Parsonnet J [editor]. Microbes and Malignancy: Infection as a Cause of Human Cancers. Oxford University Press, 1999. Reproduced with permission of the Licensor through PLSclear.)
Most new infections with HCV are subclinical. The majority (70–90%) of HCV patients develops chronic hepatitis, and many are at risk of progressing to chronic active hepatitis and cirrhosis (10–20%). In 1–5% of infected individuals, HCV leads to hepatocellular carcinoma, which is the fifth most common cause of cancer worldwide. About 25,000 individuals die annually of chronic liver disease and cirrhosis in the United States; HCV appears to be a major contributor to this burden (∼40%).
The virus undergoes sequence variation during chronic infections. This complex viral population in a host is referred to as “quasi-species.” This genetic diversity is not correlated with differences in clinical disease, although differences do exist in response to antiviral therapy according to viral genotype.
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