Hepatitis C (HCV) has enormous medical, social, and economic impact. It is estimated that 3.9 million Americans have been infected with HCV. HCV is responsible for 40% of all chronic liver disease and hepatocellular cancer in America. At least 75 percent of patients with acute hepatitis C ultimately develop chronic infection, and most of these patients will progress to some form of chronic liver disease. Liver failure resulting from HCV induced chronic liver disease is the primary indication for liver transplant in the USA today. Hepatitis C causes an estimated 10,000 to 12,000 deaths annually in the United States. When taken together, acute and chronic HCV infections are thought to amount to over $600 million in annual medical and work-loss related costs.
The number of new HCV infections have decreased by more than 80% since 1989. At that time, blood banking procedures including screening for high risk donors, testing for HCV and treating blood products to inactivate viruses were implemented. CDC estimates that during the 1980s, an average of 230,000 new infections occurred each year. Most of these new infections were as a result of blood transfusion. Today, sharing of needles and syringes is responsible for the majority of new infections.
Many of the infected are unaware of their disease. Acute HCV infections are often asymptomatic and it may take 10-20 years to develop the chronic liver disease associated with the chronic HCV infection. Throughout this period, patients are infectious and able to transmit the disease through blood to blood contact.
The existence of a third hepatitis virus was only a theory in 1974. This "non-A, non-B" hepatitis was not identified as HCV until 1988. Since HCV was identified, it has been determined that 90% of all non-A, non-B hepatitis cases were, in fact, HCV. It is now believed that as many as 242,000 Americans were infected annually during the 1980's.
While the rate of new infections has fallen since 1989, approximately 35,000 to 40,000 new infections occur annually in the USA. Almost 4 million Americans (1.8%) have been infected, and 2.7 million have the chronic form of the disease. Most of the chronic carriers are not aware that they are infected because the consequences of HCV infection are often not evident until 10 to 20 years after infection.
Currently, HCV is responsible for as many as 12,000 deaths annually in the United States. That number is projected to triple, as the late 1980's cohorts enter the end-stage of chronic liver disease. Currently, most HCV-infected people are aged 30-49 years.
Hepatitis C is a ribonucleic
acid (RNA) virus in the Flaviviridae family. RNA based viruses, like HCV,
store their genetic code within ribonucleic acid, rather than DNA. HCV's RNA
is protected within a lipid coat that allows it to fuse to the host cell's
outer membrane and merge with it. The virus's lipid coat essentially becomes
part of the host cell membrane, depositing the virus RNA inside. Once inside,
the virus takes over the host cell and begins to create viral components.
The newly created viral components attach to the inside of the host membrane.
When the components attach, they deform the membrane causing it to bulge out,
creating a bud. The bud pinches off from the host and a new virus is released.
This process continues over and over again until the cell is exhausted and
dies. Once outside the host cell, the new virus contacts a new host and begins
replication, each time creating many, many new viruses.
RNA viruses, like HCV, HIV and Influenza A, are notorious for their ability to mutate and confound vaccines and treatments. HCV's RNA amino acids differs from DNA by only one base. It is composed of adenine, guanine, cytosine and uracil, rather than thymine. It is also a single strand rather than a double. Being a single strand means that it's elements don't have to match up with a complimentary base on an opposing strand, as does DNA. One base can often be substituted for another without corrupting the virus. A substitution usually results in a protein of a slightly different shape. It is the change in shape that confounds vaccines and drugs by moving the position of binding sites.
Researchers have found that half of the virus's mutations are in sites that our immune system attacks. As the virus mutates, it changes the location of the binding site that our immune system can recognize. It can then change back to the “ancestral” set of amino acids. That is, when the virus is under attack, it changes, and then when it's safe, it changes back. Thus, if the virus moves from one host to another, it may lose the mutations that it needed to escape the immune system of the first host, if they aren't needed in the second host. Researchers have found that the mutations are not random, as had been earlier assumed, and the viruses in different people infected by the same ancestral virus have similar genetic elements and mutations. This new information could make it easier to target a vaccine in the future.
Hepatitis C is not caused by one single type of organism, but a range of viruses that are similar enough to be classified as HCV, but different enough to be classified as subgroups. There are main types of Hepatitis C that are called genotypes, and there are subtypes of those. Some viral differences are not significant enough to form another sub-type, and these are known as quasi-species. It is believed that within an HCV sub-type, there may be several million quasi-species. All this variation affects response to treatment and progression of the disease. Some researchers classify all HCV into 6 genotypes and others into 11. HCV is classified according to the genotype (1 to 11) as well as the subtype (1a, for example):
|
Genotype/Subtype
|
Geographic
distribution
|
|
1a
|
North &
South America, Australia (most common in US)
|
|
1b
|
Europe &
Asia
|
|
2a
|
Japan &
China
|
|
2b
|
US and Northern
Europe
|
|
2c
|
Western
& Southern Europe
|
|
3a
|
Australia
& South Asia
|
|
4a
|
Egypt
|
|
4c
|
Central
Africa
|
|
5a
|
South Africa
|
|
6a
|
Hong Kong,
Macau, & Vietnam
|
|
7a, 7b
|
Thailand
|
|
8a, 8b,
9a
|
Vietnam
|
|
10a &
11a
|
Indonesia
|
The distribution of genotypes in the United States involves primarily the
genotypes 1, 2, and 3:
|
Genotype
|
Percentage
of total HCV cases in US
|
|
1a
|
36%
|
|
1b
|
38%
|
|
1a & 1b
|
1%
|
|
2a
|
6%
|
|
2b
|
9%
|
|
1 & 2
|
2%
|
|
3
|
6%
|
|
4
|
1%
|
Since type 1 is not as amenable to treatment as type 2 and 3, the large number of Americans with genotype 1 has implications for treatment and prognosis.