Hepatitis C virus (HCV) is a recent field of research but a major cause of disease. What used to be known as “non-A and non-B hepatitis” was recognized in the mid-1970s with the development of serological tests for the hepatitis A and B viruses, and the cause was identified and named in 1988. Researchers are only beginning to understand the interaction of HCV with the host and the ensuing immune responses. With the technology now available in the areas of recombinant antigen production, adjuvants, and genetic immunization, researchers hope to have at least some impact on transmission and disease development at some point in the future.
Burden and Epidemiology. HCV is a truly global problem and is the major infectious disease problem in Japan. In the United States, there have been 150,000 new cases of HCV infection per year for the past decade. From 50 percent to 60 percent of these infections progress to persistent viremia and chronic persistent hepatitis. Of patients with chronic hepatitis, about 20 percent will progress to cirrhosis, and about 20 percent of cirrhotics with HCV will undergo liver failure. As a result, HCV is most common cause for liver transplantation in the United States. In addition, it is now clear that hepatocellular carcinoma is associated with HCV, with cirrhosis as a precondition, and that about 10 percent of cirrhotics with HCV will develop cancer over a period of time.
Research in Japan indicates that mean time from infection to cirrhosis is 20 years, and to cancer 30 years, so this is a very indolent type of disease. At the same time, research at NIH indicates that in a minority of patients cirrhosis can develop in a few years. Conversely, around 15 percent of post-transfusion HCV infections become negative over the long term, so there are some spontaneous resolvers.
The biggest risk factor for contracting hepatitis C is intravenous drug use, constituting about half of U.S. infections. About 30 percent to 40 percent of cases have no known risk factor. Transfusion is now a negligible risk, with the introduction of a blood screening test. There is a measurable incidence in health care workers who are exposed to infected blood, and data from Japan indicated that mothers can transmit the virus to their babies. The issue of sexual transmission is controversial, but studies show that multiple heterosexual partners are a risk factor, while the incidence in homosexual men is extremely low; apparently HCV can be transmitted sexually, but it is inefficiently transmitted that way.
Viral Genome. HCV belongs to the Flaviviridae family, along with flavivirus and pestiviruses. It is an RNA virus that does not integrate into cellular DNA, and instead replicates only through RNA replication intermediates. The virus is highly heterogenous: it can change rapidly in the infected host, and at