According to data from the Centers for Disease Control and Prevention (CDC), the most common risk factors for HCV infection are as follows:
Having had surgery within the last 6 months
Multiple contacts with an HCV-infected individual
Employment in the medical or dental field
Currently, transmission of HCV by blood transfusion is close to zero in the United States; the risk for acquiring HCV by needle stick is about six times higher than that for HIV (1.8 vs. 0.3%). For children, the major route of infection is vertical perinatal transmission from the mother. Some patients have multiple risk factors, but one-third of http://ebooksmedicine.net individuals have no identifiable risk factors, an enduring mystery.
HCV, discovered in 1989, is a member of the Flaviviridae family. Just as in the case of HIV, an understanding of viral replication and assembly has facilitated the development of highly effective anti-HCV drugs (described below). HCV is a small, enveloped, single-stranded RNA virus with a 9600-base genome encoding a single polyprotein that is processed by several proteases into 10 functional proteins. Included among these viral proteins is a viral protease that is needed for complete processing of the polyprotein; NS5A, a protein that is essential for assembly of HCV into mature virions; and a viral RNA polymerase that is necessary for replication of the viral genome (
Fig.
16.11 ). Because of the low fidelity of the HCV RNA polymerase, the viral genome is inherently unstable, giving rise to new genetic variants at a high pace. This has led to the appearance of six major HCV genotypes worldwide, each with one or more “subspecies.” Infections in most individuals are due to a virus of a single genotype, but new genetic variants are generated in the host as long as viral replication persists. As a result, each patient usually comes to be infected with a population of divergent but closely related HCV variants known as quasispecies.
The incubation period for HCV hepatitis ranges from 4 to 26 weeks, with a mean of 9 weeks. In about 85% of individuals, the acute infection is asymptomatic and goes unrecognized. HCV RNA is detectable in blood for 1 to 3 weeks, coincident with elevations in serum transaminases (
Fig. 16.12 ). In symptomatic acute HCV infection, anti-HCV antibodies are detected in only 50% to 70% of patients; in the remaining patients, the anti-HCV antibodies emerge after 3 to 6 weeks. The clinical course of acute HCV hepatitis is milder than that of HBV. It is not known why only a small minority of individuals is capable of clearing HCV infection.
Persistent infection and chronic hepatitis are the hallmarks of HCV infection, despite the generally asymptomatic nature of the acute illness. In contrast to HBV, chronic disease occurs in the majority of HCV-infected individuals (80%–90%), and cirrhosis eventually occurs  in as many as one-third. The mechanisms leading to  chronicity are not well understood, but it is clear that the virus uses multiple strategies to evade host anti-viral immunity. In addition to rapid generation of genetic variants, which may allow the virus to elude neutralizing antibodies, HCV encodes proteins that inhibit Toll-like receptor and interferon signaling in hepatocytes, activites that would otherwise allow hepatocytes to resist viral infection.
In chronic HCV infection, circulating HCV RNA persists in 90% of patients despite the presence of neutralizing antibodies (see