Hepatitis C virus characteristics and clinical significance

Hepatitis C

What is the leading cause of liver disease? What could cause so many people to require liver transplants? Most people on the street today would think that the answer to those questions would be alcoholism. And, although alcohol does do its fair share of damage to livers around the world, there is a greater source causing chronic liver disease out there.

This term paper will attempt to shed light on the hepatitis virus. The correct pronunciation would be: (h-p ? t? t-s). There are several strains of the hepatitis virus with some being non-issues and others being incurable killers. This report focuses specifically on the Hepatitis C virus which falls under the incurable killer header. This strain of the viruses can never be taken lightly.

There are many ways for an individual to acquire the hepatitis C virus into their system; however, there is currently no cure once it has been introduced into the system. When someone contracts the disease associated to the hepatitis virus, consider that 75 to 85% of those infected individuals will develop chronic liver disease and of that percentage 1 to 5% of the infected individuals may die from liver related complications. This report will attempt to present some history of the virus; its molecular structure; the replication of genome; modes of infection and finally some treatment methodologies.

History

Around 1989, after Scientists finally understood that the human immunodeficiency virus was the major cause of AIDS, another break through occurred. "...a second virus which causes persistent infection -- hepatitis C, or HCV was identified." (Askari and Cutler) Prior to the hepatitis C virus being identified, the majority of cases regarding liver failure were called "cryptogenic," or in laymen terms - 'we ain't got a clue.' In hindsight, scientists now know what caused the so called cryptogenic diseases of the liver. The disease must have been infecting us humans for a long time. Today, of course, doctors know that hepatitis C was and continues to be the main cause of chronic cirrhosis, liver failure and liver cancer. Similar to many human immunodeficiency virus infections, the hepatitis C viral infection has been proven to lay dormant in carriers for many years without demonstrating symptoms. "What is striking about hepatitis C, in contrast to human immunodeficiency virus, is that about 2% of the United States population was already infected with hepatitis C when the virus was first discovered. HIV is 4-fold less common in this country." (Askari and Cutler)

Scientists now know that a number of viruses can cause acute viral hepatitis in humans. There have been five strains identified to date and they have been classified as hepatitis A through E. Apparently there are more strains yet to be discovered by the scientific community has at least ten other viruses currently under the radar. Hepatitis C causes an inflammation of the liver and is currently incurable. An individual can get the viral infection from various sources "including: viruses, toxic chemicals, alcohol consumption, parasites and bacteria, and certain drugs. Symptoms of hepatitis are nausea, fever, weakness, loss of appetite, sudden distaste for tobacco smoking, and jaundice."(The Columbia Encyclopedia) But, when we consider Hepatitis C, we must first understand the A and B. strains so as to aid in the explanation of how we got to where we are today with some semblance of order.

Hepatitis A, often called infectious hepatitis, has been known to occur during epidemics because the virus is prevalent in human feces. The A strain is easily transmitted through food that was prepared by an individual already infected with the virus who has not washed their hands. Those signs that we hopefully see in a restaurant's restroom that state 'All Employees Must Wash Their Hands' can be attributed to this type of virus. Of course active infections are also easily spread through physical contact but the disease usually is one that usually resolves itself. As of 1995, a vaccine made gamma globulin is available but is instituted only in very serious cases because one would need to get an injection by a physician.

Hepatitis B, often called serum hepatitis, is more difficult to get than the A strain because it is usually a passed through needles. Until the mid-1970's, Hepatitis B was known to be commonly transmitted to patients during blood transfusions. Today there are specific blood and plasma screening techniques that can identify the strain and therefore prevent these types of infections. Although effective, these screening tests can not totally eliminate the B. strain.

The problem is that intravenous drug users continue to spread the disease because they are in the habit of sharing contaminated needles. Other ways to get the B. strain include partner to partner sexual transmission and also from mother to baby during birth. "Some infected individuals, particularly children, become chronic carriers of the virus. Hepatitis B can progress to chronic liver disease and is associated with an increased risk of developing liver cancer." (The Columbia Encyclopedia) A vaccine, available since 1981, is recommended for all infants and others at risk for the virus. Alpha-interferon was approved as a treatment in 1992.

Hepatitis C is newly named. The virus used to be simply called non -- A or non-B hepatitis. Like its cousins, the C. strain can be transmitted through blood transfusions and of course by sharing dirty needles. But, the problem with this particular strain is that in many cases the medical community cannot actually identify a specific source of the disease. "Many of those infected have no symptoms but become carriers, and the virus may eventually cause liver damage. Blood banks routinely screen for hepatitis C" (The Columbia Encyclopedia) Hepatitis C has been identified as the main cause of liver disease and it has also recently become the most common form of chronic liver disease. There is no cure for the disease but doctors have recently begun treating the virus infection with Alpha-interferon. Another approach is the shot gun approach where a combination of a drug named ribavirin is used in conjunction with Alpha-interferon.

Some statistics relating to the viral infection demonstrate the trends of the nation. "Number of new infections per year has declined from an average of 240,000 in the 1980s to about 25,000 in 2001. Most infections are due to illegal injection drug use. Transfusion-associated cases occurred prior to blood donor screening; now occurs in less than one per million transfused unit of blood. Estimate'd 3.9 million (1.8%) Americans have been infected with HC V, of who m 2.7 million are chronically infected." (Viral Hepatitis C)

Molecular structure

When scientists understand the structure of enzymes for a virus such as hepatitis C, they can then design and eventually create drugs with the sole intent of disabling those enzymes. Around mid-1991, Schering-Plough made the exciting announcement that it had actually identified the molecular structure of the hepatitis C virus and the key enzymes the virus used to grow and replicate. Those enzymes announced were the key enzymes of protease, helicase and polymerase. By the end of 1991, Schering-Plough introduced the new drug Intron A which was cousins of the multiple sclerosis cure all called interferon, attacked the hepatitis C enzymes which were identified only a few short months prior. The drug as predicted blocked the hepatitis C virus' ability to grow and replicate. Intron A went on to become the first drug approved in the United States by the food and drug administration for specifically treating hepatitis C

Replication of Genome

It is much easier to distinguish the hepatitis C virus as though it was a single organism. The problem is that the virus has a range of viruses all similar enough to be called the hepatitis C virus but different enough to be classified into minor subgroups. "Viruses are microscopic and no person could ever see them with the naked eye. Indeed, HCV is so small that there's been no confirmed actual sighting of it using any type of microscope yet developed." (Hepatitis) Scientists have a better way of classifying the virus.

They classify them by their 'genotypes' and 'subtypes.' Imagine a group of cats we call 'felines ' that have evolved over time into different types of cats. These levels would be the Genotypes. The subtypes would be a Siamese cat and a black cat. Both are cats but they are not totally equal.

Most scientists believe that the hepatitis C virus evolved over a several thousand years and that is why there are unique global patterns of genotypes and subtypes:

1a - mostly found in North & South America; also common in Australia

1b - mostly found in Europe and Asia.

2a - is the most common genotype 2 in Japan and China.

2b - is the most common genotype 2 in the U.S. And Northern Europe.

2c - the most common genotype 2 in Western and Southern Europe.

3a - highly prevalent here in Australia (40% of cases) and South Asia.

4a - highly prevalent in Egypt

4c - highly prevalent in Central Africa

5a - highly prevalent only in South Africa

6a - restricted to Hong Kong, Macau and Vietnam

7a and 7b - common in Thailand

8a, 8b & 9a - prevalent in Vietnam

10a & 11a - found in Indonesia

It's believed that of the estimated 160,000 Australians with HCV, approx. 35% have subtype '1a', 15% have '1b', 7% have '2', 35% have '3' (mostly being 3a). The remaining people would have other genotypes." (Hepatitis)

The Replication of Genome provides insights into the Hepatitis C virus which falls under the family of Flaviviridae with a genus of Hepacivirus. "Nearly 4 million individuals in the United States are infected with HCV. About 30,000 new infections are diagnosed each year, and 8000 infected people die." (Burke, Dhopesh, and Taylor)

As noted, drug use accounts for almost half of all new identified infections on an annual basis and could perhaps add up to well over half of the chronic infections. "Of those with hepatitis C, 20% may develop cirrhosis within the subsequent 10 to 20 years. This susceptibility is increased by excessive alcohol consumption." (Burke, Dhopesh, and Taylor) The following table comes from the Bacteriology web site and provides the details associated with Replication of Genome:

Characteristics: enveloped; pos pol RNA genome; E1 and E2 envelope proteins; genome codes for 2 proteases and a RNA-dep-RNA-pol

Replication: similar to other Flaviviruses (?); genome encodes for a polyprotein that is cotranslationally processed into at least 10 proteins (4 structural and 6 nonstructural proteins); may replicate in cells other than hepatocytes; multiple genetic variants recovered from single individual

Pathogenesis: transmitted predominantly by blood (transfusions, iv drug use); high percentage (~80%) of infections become chronic; incubation 2-26 wks (average 6-12 wks)

Infections: Hepatitis (acute with resolution, chronic that is stable or results in cirrhosis [stable, progressive, or carcinoma])

Control/prevention: block transmission; chronic treated with? IFN or? IFN + ribavirin" (Bacteriology)

Mode of infection

HCV is spread through the sharing of needles or when "shooting" drugs. The needlesticks are the problem because blood as a residue remains on the open end of the needle shaft. It is therefore quite obvious to doctors and scientists that that injection drug users are susceptible to a number of infections because of the passing of blood-borne viral infectious through the needles. Diseases like the human immunodeficiency virus and viral hepatitis are among the list.

Since the discovery of human immunodeficiency virus, the health related education and the bulk of the media attention have focused mainly on the prevention of HIV. "It was the empirical observation of our unit staff that a large number of patients were hepatitis C virus positive. These patients, however, had very little knowledge of hepatitis, especially of the mode of transmission of hepatitis viruses." (Burke, Dhopesh, and Taylor)

Reliable blood screening for Hepatitis C became available in June 1992. As a result, the chances of contracting Hepatitis C from transfusions has dropped to less than 1 in 100,000." (Larson) As noted, there are many ways to get hepatitis C but there are some at greater risk than others. Someone who receives a blood transfusion and is notified by the source such as the Red Cross that the blood from a donor was later tested as positive for hepatitis C is obviously a candidate over someone who has never received a transfusion. People that have tried drugs that need an injection such as heroin users, even if they only did it once many years ago, are in a high risk bracket. In this case, frequency does not matter because it can happen the first time. Other factors for getting the viral infection include: blood transfusion or solid organ transplants prior to July, 1992; recipients of plasma-based clotting factors created prior to 1987; long-term kidney dialysis patients; and, individuals showing any signs of liver disease.

But other scary factors pertain to the hepatitis C strain. Some people simply do not know how they were infected. "She did not have any of the common risk factors, which include blood transfusions prior to 1992, tattoos, history of intravenous drug use, hemodialysis, use of intranasal cocaine, or history of promiscuous sexual activity. In up to 20% of people, it is not possible to identify a clear source for the infection." (Askari and Cutler)

Doctors also realize that because the disease can be a sexually transmitted disease, certain promiscuity can put an individual at risk. It is often asked if latex condoms are effective in preventing the transmission of the disease but doctors just do not know at this time. The problem is that if one was to kiss intimately while wearing a condom, the overall safety factor may be totally eliminated for preventing infection with HCV. Transmission occurs when blood or body fluids from the infected individual enters the body of an uninfected person

Current and Potential Treatments

Prevention is the best treatment -- not getting the viral infection in the first place is the best cure when it comes to hepatitis. There is no vaccine to prevent hepatitis C Therefore, it would be a good idea for those in high risk groups to know the signs and symptoms associated with hepatitis C infection. If a person is in a high risk group such as intravenous drug addict, do not shoot drugs. If the person is compelled to shoot drugs, they should try and stop with the help of a treatment program.

Of course this advice is non-sense to a dedicated drug abuser. So, if the dedicated individual cannot stop, they should never share needles, syringes, water, or "works." A suggestion of getting the necessary vaccinations against hepatitis A and B. would also be a good idea. But if tall that fails, the signs and symptoms of a hepatitis related disease can be looked for. The signs are: