The in vitro culture of hepatitis C virus and approaches to the control of replication

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HCV is a major cause of liver disease and around 200 million people are currently infected worldwide, including 200,000 Australians. HCV differs to other flaviviruses. Most notably, around 80% of individuals develop a persistent infection, accounting for the large number of carriers. This infection is probably life-long and 40-50% of carriers will develop serious liver disease, including liver cancer. HCV is currently the leading single indicator for liver transplantation in the western world. These carriers can also transmit the virus to uninfected individuals. Screening in the blood banks has reduced transmission after blood transfusion to virtually zero. However, although individuals who share contaminated needles represent a major high risk population, around 30% of carriers have no acknowledged transmission risk factors, and transmission to patients in hospitals has been recognised. As a result, it is clear that members of the general population may still become infected. It has been estimated that there are 10,000 new cases each year in Australia. The best available treatment is a combination of interferon-alpha and ribavirin, but this is only successful in 40-50% of carriers. Moreover, many patients fail to tolerate these drugs and the cost restricts treatment to a small proportion of carriers. As a result,only approx 6,500 carriers have been treated in Australia. A huge backlog in the liver clinics and the resistant nature of the virus in 50% of patients in Australia mean that these patients will not be treated unless new therapies are developed. The most effective means to prevent virus infections is by vaccination. Thus the development of novel antivirals and a vaccine for HCV are priorities. Since the cost of a single liver transplant is $100,000 the development of such agents is likely to be cost effective. However, it is necessary to develop suitable cell culture systems to test putative antiviral agents.