MicrobiologyBytes

Hepatitis is inflammation of the liver and can be caused by a variety of environmental or infectious agents. There are at least five different viruses which specifically infect human livers and cause hepatitis. These days, they are named hepatitis viruses A to E (HAV, HBV, …).
Hepatitis C virus (HCV) was first identified by molecular cloning of the virus genome in 1989 (Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359-62, 1989).

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The HCV genome consists of a positive-sense RNA molecule approximately 9.6 kb in length. HCV is a member of the Flaviviridae and is the only member of it’s genus (Hepacivirus).

It has been estimated that 2.2% of the world’s population, approximately 170 million people, are infected with hepatitis C.
Blood-borne infections are most prevalent, with high rates seen in intravenous drug abusers, and recipients of unscreened blood transfusions and blood products. The possibility of sexual transmission has not been eliminated, but if it occurs, the risk seems to be very low. Vertical transmission of HCV from mother to child occurs at a rate of 5-10%. This risk can be significantly lowered if babies are delivered by caesarean section. However, breast feeding does not appear to be a significant risk factor to children with infected mothers. Over 4 million people in the USA are infected with HCV, a prevalence rate of 1.6 %. The peak prevalence of HCV infection occurs among people of 40 to 49 years of age and a history of injection drug use is the strongest risk factor (The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 144: 705-714).
The UK Health Protection Agency’s annual reports on HCV estimate that in England and Wales around 4,500 people are suffering from severe liver disease due to chronic HCV infection, and that this could rise to around 7,000 by 2010. Over 200,000 UK residents have chronic HCV infection, but five out of six are unaware of this. It is believed that around 80% of UK HCV infections are linked to the use of injected drugs, and 50% of injecting drug users are infected with HCV.

The majority of cases of HCV infection give rise to an acute illness, but up to 80% may then develop into chronic hepatitis. Almost all patients develop a vigorous antibody and cell-mediated immune response which fails to clear the virus infection but may contribute to liver damage. Spontaneous resolution of chronic liver disease is very rare (<2%) and patients with chronic disease are at risk of developing hepatocellular carcinoma (HCC). However, some studies have suggested that infection may have a more benign outcome, at least in some populations (Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol. 2004 12: 96-102).

Until recently, HCV could not be cultured in vitro and this hampered investigation of the virus. As an example of how difficult HCV is to study, this virus has still not been definitively imaged by electron microscopy and its fine structure remains to be determined. However, during the last few years, powerful model systems have been developed to study the HCV replication cycle (Replication of hepatitis C virus. 2007 Nature Reviews Microbiology 5: 453). Much work still remains to be done with respect to understanding virion assembly and structure, the stages of replication and the mechanism by which the RNA genome is replicated.

Treatment of HCV infection is very difficult and the current standard therapy, pegylated interferon-alpha combined with ribavirin, is often difficult for patients to tolerate and results in a sustained virus reduction in only about half of patients. HCV can be classified into several genotypes based on variations in the nucleotide sequence of its genome. The infecting HCV type has been shown to be clinically important because it predicts responses to antiviral therapy, with infection by type 1 being associated with the most resistance to treatment. Spontaneous virus clearance may occur more often with HCV type 1 infection than with other genome types, although type 1 infection may also be more aggressive than genome types 2 or 3 (Does the clinical outcome of hepatitis C infection vary with the infecting hepatitis C virus type? J Viral Hepat. 2007 14: 213-20).

Compared with other types of viral hepatitis such as hepatitis A and hepatitis B, development of vaccines against HCV infection has been difficult. Some of the reasons for this are that HCV seems to elicit a weak immune response which does not protect against infection, and also the considerable genetic and antigenic variability of the virus. In these respects, HCV is reminiscent of HIV. Nevertheless, some progress has been made and HCV vaccine candidates are being tested in humans. One of these consists of a recombinant form of the HCV envelope proteins (E1 and E2) expressed in mammalian cells. This vaccine has been shown to offer partial protection to chimpanzees, specifically, in protecting them from becoming chronically infected. Other candidate vaccines are composed of proteins from the nonstructural region of the HCV genome, which stimulate more of a cellular rather than a humoral immune response. Finally, some therapeutic vaccines are being tested for their possible value in the treatment of chronic HCV infection.

Although some progress has been made in attempts to prevent HCV infection, a truly effective vaccine still appears to be a considerable way off. With the number of diagnosed cases still increasing, we have a mountain to climb.

Update: Mitchell Shiffman of Virginia Commonwealth University has recently announced a “cure” for HCV. Standard therapy with pegylated interferon and ribavirin is said to have removed all detectable virus in 99% of patients for up to seven years. This result conflicts with other trials of this therapy, where response rates are encouraging but lower than 99%, and so needs to be treated with optimistic caution until it is confirmed.

This entry was posted on Monday, May 21st, 2007 at 9:05 am and is filed under Biology, Biotechnology, HIV/AIDS, Health, Immunology, Medicine, Microbiology, Podcast, Science, Vaccines, Virology. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.