Hepatitis C historical perspective
Hepatitis C historical perspective On the Web
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The discovery of the hepatitis C virus was made based on early findings of patients with signs and symptoms of viral hepatitis lacking positive serologies for hepatitis A or B. These patients were originally described in 1974-5 as having "non-A, non-B viral hepatitis" (NANBH). It was not until 1989 that hepatitis C virus (HCV) was truly discovered when Qui-Lim Choo and colleagues successfully isolated the first cDNA clone 5-1-1 derived from the NANBH genome. The first interferon-alpha (INF-a) to treat HCV was developed in 1986 and approved in 1991. Approximately 10-15 years later, global efforts to reduce the burden of HCV were launched; worldwide campaigns were led by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC).
Discovery of Non-A, Non-B Viral Hepatitis
In the early 1960s, scientists only differentiated between hepatitis A, an acute infection of short incubation period transmitted via the fecal-oral route, and hepatitis B, a potentially chronic infection of long incubation period transmitted via blood exposure. Consequently, the discovery of hepatitis C only occurred with the availability of diagnostic assays in the early 1970s. In 1974-5, the works of Alfred Prince, Stephen Feinstone, and Harvey Alter led to the new discovery that was termed "non-A, non-B viral hepatitis" (NANBH) when serological markers for hepatitis A and B were both absent in patients with signs and symptoms of viral hepatitis. Shortly after, studies scrutinizing the new discovery revealed that most patients with NANBH had been exposed to blood transfusions and hepatic cirrhosis ensued in as many as 20% of these patients.
With no techniques available with which to isolate the virus, the infective potential and mode of transmission of NANBH were later confirmed in 1978 when chimpanzees were infected with the virus following injection of human blood from patients confirmed to have the disease. Experiments using chimpanzee models contributed to the discovery of various NANBH variants and agents, and allowed scientists to study the pathological aspects of hepatic injury in these infections.
Discovery of Hepatitis C Virus
The attempt to discover the first NANBH antibodies persisted for several years. Although the virus was originally described in the early 1970s, the identification of NANBH-specific antibodies did not occur until 1985 by Yohko Shimizu and colleagues. In 1989, the full isolation of a cDNA clone 5-1-1 derived from NANBH genome was finally successful. Qui-Lim Choo and colleagues were able to construct a random-primed complementary DNA (cDNA) from plasma containing an NANBH agent, showing that the virus is a positive-stranded RNA molecule composed of of 10,000 nucleotides. With the isolation of the new agent, hepatitis C virus (HCV) was discovered and the term replaced NANBH for the first time in 1989. In the early 1990s, HCV was then classified into 6 major genotypes and several subtypes. Due to similarity with other RNA viruses, it was considered a type member of the genus Hepacivirus within the family Flavividae.
Sequelae Following HCV Discovery
Following its discovery, blood tests were available by 1990 to detect the presence of HCV in blood products, to determine chronicity, and to reveal its association with such cancers as hepatocellular carcinoma and non-Hodgkin's lymphoma. Worldwide efforts to prevent the transmission of HCV have been somewhat successful in reducing the global burden of HCV.
Global Awareness Campaigns
In 2007, the World Health Organization (WHO) declared July 28 "World Hepatitis Day" and the Centers for Disease Control and Prevention (CDC) launched its national "Know More Hepatitis" campaign on July 28, 2011 to educate individuals born between 1945-1965 about HCV and launched its "Hepatitis Testing Day" on May 19, 2012.
Even before the identification of the virus in 1989, the first effort to develop interferon-alpha (IFN-a) treatment against HCV was initiated in 1986 by Jay Houston Hoofnagle and colleagues. The drug was finally approved by the Food and Drug Administration (FDA) for HCV treatment in 1991 at a dose of 3 million units subcutaneously three times weekly for 6 months. Ribavirin was first used to treat HCV in 1997; the drug demonstrated a decrease in aminotransferase levels and a good safety profile, despite its lack of antiviral activity as monotherapy. The FDA approved the use of combination therapy of interferon alpha and ribavirin in 1998. Finally, pegylated interferon, which has a higher concentration and longer half life than interferon, was approved for use in 2001. Newer HCV protease inhibitors, such as telepravir, were developed in 2007.
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