Academic journal article Proceedings of the American Philosophical Society

Hepatitis C: Toward a Cure and Eradication1

Academic journal article Proceedings of the American Philosophical Society

Hepatitis C: Toward a Cure and Eradication1

Article excerpt

HUMANS probably first encountered hepatitis viruses thousands of years ago. Documents from the seventeenth century to the nineteenth century record epidemics of jaundice dur- Hing wars. During World War II, there was a series of hepatitis outbreaks after mass vaccinations for measles and yellow fever. Today we know that viral hepatitis is caused by an alphabet of liver scourges-hepatitis A, B, C, D, and E viruses. The hepatitis viruses are unrelated to each other and present with different natural histories of infection. HAV, a picornavirus, and HEV, the sole member of the family Hepeviridae, are spread by ingesting contaminated food and water. Both viruses typically cause acute self-limiting hepatitis, although HEV infection can be severe and fatal in pregnant women. Fortunately, HAV can be prevented by immunization, and a vaccine for HEV is currently in clinical trials. Proper hygiene and the availability of clean water are also important in HAV and HEV prophylaxis. HBV is a Hepadnavirus that can cause acute and chronic hepatitis. The virus, which is spread by blood and other body fluids, infects about 350 million people worldwide. While HBV is vaccine-preventable and the disease can be managed with anti-viral drugs, there is no cure for persistent infection. HDV is a satellite virus that can exacerbate the symptoms of hepatitis B. A member of the Flaviviridae, HCV is a blood-borne pathogen that causes acute and chronic liver disease. An estimated 130 million people are infected with HCV worldwide. Unlike HBV, HCV can be cured, although the success rate of current treatments is less than 50%, and a vaccine for HCV is not yet available.

Discovery of Hepatitis C Virus

Controlling the various causes of viral hepatitis has been a priority since the mid-twentieth century. During that era, up to one-third of blood transfusion recipients went on to develop liver disease (1). By 1975, HAV and HBV had been discovered, and it became apparent that many post-transfusion hepatitis cases were caused by a still-unknown pathogen, termed non-A non-B hepatitis (NANBH)(2). Over the next fourteen years, researchers worked without success to identify the suspected virus. There was no reliable NANBH antigen or antibody, the infectious agent could not be cultured or seen by electron microscope, and PCR had yet to be developed. Finally, it was a blind immunoscreening approach undertaken by Michael Houghton's team at Chiron Corporation that pulled a small fragment of nucleic acid from an infectious serum-derived library (3). They called the new virus HCV.

After the discovery of HCV, it quickly became apparent that the virus harbors an immense genetic diversity. Its error-prone replication, combined with high viral loads, means that up to 1012 HCV variants can exist in an infected individual at any one time. This variation is so large that it dwarfs that of other highly mutable viruses, such as human immunodeficiency virus (HIV). Divergence of HCV sequences over hundreds of years has led to distinct "genotypes" of the virus. Currently, seven major genotypes are recognized, showing sequence divergence of 30%-35% across the complete genome (4,5). The various genotypes have diverse distributions around the globe, alterations in pathogenesis, and differing susceptibilities to treatment (5). Genotype 1 is most prevalent in Europe and North America. Genotype 4 is common in Egypt, where a schistosomiasis eradication campaign in the 1970s leftan estimated 10% of the population HCV-infected. Genotype 6 is prevalent in China, while genotype 3 is distributed across Asia.

HCV Disease and Treatment

In 1990, screening of the U.S. blood supply for HCV began. It is estimated that the first-generation HCV assay prevented more than forty thousand infections in the first year (6). In the developed world, the risk of contracting HCV from contaminated blood today is vanishingly small, and most new infections occur in injection drug users. In some regions of the developing world, however, unsanitary medical practices remain a significant source of the disease (7). …

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