Hepatitis C virus (HCV), a member of the genus Hepacivirus within the family Flaviviridae, has a slightly different genome organization and replication strategy from the members of the Flavivirus genus.  The required cofactor for NS3 protease activity is NS4A rather than NS2B as in the Flavivirus genus.  Crystal structures of the HCV protease complex, however, reveal a high degree of structural similarity with the NS2B-NS3 protease complex of the flaviviruses.

There are six known genotypes and more than 50 subtypes of Hepatitis C. Prevalent genotypes vary by geographical location and by the method of virus transmission.  The genotype of infection is therefore helpful in defining the epidemiology of Hepatitis C. More important, knowing the genotype or serotype (genotype-specific antibodies) of HCV is helpful in making recommendations and counseling regarding therapy.

HCV is a blood-borne pathogen and is transmitted by infectious blood products or nonsterile instruments that have come into contact with infected blood.   Approximately 2-3% of the world’s population is infected with HCV. An additional 3-4 million people are estimated to contract HCV every year.  Of these, 75% to 85% will develop a persistent, chronic infection.  Of those, approximately 15% to 20% will develop chronic liver disease progressing to cirrhosis. Between 1% and 5% of people with chronic infections will develop liver cancer within 20 to 30 years.

While most infected individuals show no immediate symptoms, about 25% experience nausea, fatigue, right upper quadrant pain, darkening of the urine, and jaundice when they become infected.  For many, however, noticeable symptoms do not appear for decades.  Disease pathogenesis is primarily restricted to the liver and involves a combination of viral proteins, and the immune response they elicit.  Inflammation and necrosis in the liver can ultimately lead to fibrosis, cirrhosis, and cancer.

The current treatment for HCV infection is a combination of interferon-α and ribavirin.  Unfortunately, this treatment demonstrates only modest efficacy, and is accompanied by significant clinical toxicity.