Since its discovery in 1988,<sup>25 Choo Q.L., Kuo G., Weiner A.J. , e al. Isolation of a cDNA clone derived from a bloodborne non-A, non-B viral hepatitis genome Science 1989 ;  244 : 359-362

Cliccare qui per andare alla sezione Riferimenti</sup> hepatitis C virus (HCV) has emerged as a major cause of chronic liver disease worldwide. The widespread endemicity of HCV infection is the result of a combination of factors, including those related to the genetic diversity of the virus and the host response, and specific settings and behaviors that facilitated transmission.

The vast majority of persons who contract HCV infection become persistently infected, and most also develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. The mechanism by which such a high rate of persistent infection is established appears to be related to the lack of development of an effective neutralizing immune response. Like other RNA viruses, the substantial heterogeneity of the HCV genome is the result of mutations that occur during viral replication.<sup>19 Bukh J., Miller R.H., Purcell R.H. Genetic heterogeneity of hepatitis C virus: Quasispecies and genotypes Semin Liver Dis 1995 ;  15 : 41-63  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Within an infected individual, the genetic heterogeneity of HCV consists of a population of closely related, yet heterogeneous, sequences called quasispecies, which result from the rapid development of mutations in a hypervariable region (HVR1) within one of the envelope proteins. Patients infected with HCV mount a humoral immune response to epitopes of HVR1, but sequential changes in the consensus sequence of HVR1 during infection result in the generation of variants that are not recognized by preexisting antibodies.<sup>19 Bukh J., Miller R.H., Purcell R.H. Genetic heterogeneity of hepatitis C virus: Quasispecies and genotypes Semin Liver Dis 1995 ;  15 : 41-63  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 38 Farci P., Alter H.J., Govindarajan S. , e al. Lack of protective immunity against reinfection with hepatitis C virus Science 1992 ;  258 : 135-140

Cliccare qui per andare alla sezione Riferimenti, 39 Farci P., Alter H.J., Wong D.C. , e al. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization Proc Natl Acad Sci USA 1994 ;  91 : 7792-7796  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 83 Shimizu Y.K., Hijikata M., Iwamoto A. , e al. Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses J Virol 1994 ;  68 : 1494-1500

Cliccare qui per andare alla sezione Riferimenti</sup> The generation of these neutralization escape mutants appears to be the mechanism by which the virus establishes and maintains persistent infection.

Although virus- and host-specific factors are responsible for the high rate of chronic HCV infection, the magnitude of the spread of HCV infection is primarily the result of specific factors related to transmission. Historically, healthcare-related factors that have been important in the transmission of HCV included the transfusion of contaminated blood and blood products and the reuse or sharing of contaminated equipment during the course of both traditional and nontraditional medical procedures. The most important human behavior related to the transmission of HCV has been injection drug use, which in many developed countries has been the leading source of HCV infection during the past 20 to 30 years.

The clinical importance of HCV infection was recognized only recently, and attention and resources have been rapidly directed toward developing new and improved therapies. The perception of the public health importance of HCV infection is still limited. Despite the knowledge that injection drug use is the major source of HCV infection in the United States, this message has not been included in prevention and treatment programs, and the resources needed to support strong public health programs have yet to be identified.