Table 1.

Hepatitis C: the basics.

Virus classification and structure	Hepatitis C virus (HCV) is the only member of the genus Hepacivirus in the family Flaviviridae. There are 6 major HCV genotypes; about 80% of patients in the US have genotype 1. The 9.6 kb single-stranded, positive-sense RNA genome encodes a single open reading frame flanked by 5′ and 3′ untranslated regions.
Infection Cycle	A number of hepatocyte surface molecules, including CD81 tetraspanin, scavenger receptor class B type I (SR-BI), Claudin-1, mannose-binding lectins DC-SIGN and L-SIGN have been identified as putative HCV receptors or co- receptors. Upon entry and uncoating of the virion, the plus-sense viral genome acts as messenger RNA. Translation is initiated at an internal ribosome entry site (IRES) located within the 5’ UTR. The 3,011 amino acid polyprotein is then co-and post-translationally cleaved into the viral structural and nonstructural proteins both by host signal peptidases and viral proteases. HCV structural proteins include the nucleocapsid core (C) and two envelope glycoproteins, E1 and E2. The non-structural proteins include a zinc-dependent metalloprotease encoded by the NS2-NS3 region, an NS3 serine protease-RNA helicase along with the NS4A peptide cofactor of NS3 protease activity, the NS4B phosphoprotein, and p7. The replicase complex includes the NS5A protein and the NS5B RNA-dependent RNA polymerase which is responsible for catalyzing viral RNA replication.
Epidemiology	HCV infects only humans. There are no approved vaccines. The virus is transmitted through blood transfusion, injecting drug use or other types of direct blood contact. Nearly 200 million people are infected worldwide. In the United States, there are estimated to be some 3.2 million infected persons, with about 20,000 new cases a year. Rates of HCV infection are higher among people infected with HIV.
Clinical course	A minority of patients develops mild, nonspecific symptoms during the months following infection, but most remain asymptomatic. Some 15–25% of patients are able to eliminate the virus without treatment. Chronic HCV infection is diagnosed on the basis of anti-HCV antibodies, PCR testing for circulating virus and the detection of abnormal liver function. The CDC estimates that for each 100 people with HCV, 75–80 will become chronically infected, 60–70 will develop liver disease, 5–20 will develop cirrhosis over a period of 20–30 years, and 1–5 will die of the consequences of viral infection.
Antiviral therapy	Antiviral therapy is initiated when progressive disease is indicated by biopsy and abnormal liver function tests. Current therapy consists of a combination of pegylated interferon alpha and ribavirin. Patients with genotypes 2 and 3 have a 60–80% response (disappearance of detectable HCV RNA in serum) to either a 24- or 48-week course of combination therapy, while the rate is 30–50% for genotype 1.