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July 31, 2006

Understanding Hepatitis C Interferon Therapy

Whether you are a candidate for interferon therapy or simply want to learn more about the most common medical treatment for viral hepatitis, this article can be your introduction to how it works, and more importantly, how effective it is.

Understanding Hepatitis C Interferon Therapy
July 31, 2006
LiverSupport.com
Nicole Cutler, L.Ac.

Interferon is a cytokine, a specific protein that is no stranger to the human body. In fact, the human body is constantly making interferon, and makes even greater amounts when trying to fight off an intruder, such as a virus. People experience this when suffering with the flu. When sick with the flu, the body makes extra interferon to defeat the virus causing the illness. The extra interferon causes symptoms such as fever, nausea, achy and sore muscles, joint pain and fatigue. This is called an antiviral effect. Interferon therapy is currently the gold standard in treatment for certain types of hepatitis B and C.

How Does it Work?

While the interferon used for hepatitis treatment is slightly different from the kind made in the body, it helps defeat the virus in three ways:

1. By attaching to healthy cells to help defend against invading viruses.

2. By helping the immune system to stop the virus from multiplying.

3. By assisting the body in ridding itself of infected cells while preventing healthy cells from being infected.

Interferon helps the body distinguish between cells infected by the virus and non-infected cells, targeting infected cells for destruction. For unknown reasons, a virus in the liver often becomes invisible to the immune system. If your body can't see the virus, it can't destroy it. This invisibility permits the virus to multiply within the liver, fostering a more chronic and severe infection. Scientists have learned that if they gave synthetic (created through genetic engineering) interferon to a person with chronic viral hepatitis, they could increase the immune system's ability to detect, or see, the infection. Imagine liver cells blending in with invaders, both a clear transparent color. The addition of interferon is like staining the infection deep red, highlighting them so they can be targeted for the immune system’s fighter cells. Interferon also helps patients with viral hepatitis by directly suppressing the formation of new virus particles within the liver.

What kinds are there?

Scientists have determined that the body makes three distinct types of interferon; alpha, beta and gamma interferon, each containing several members. Alpha interferon has been approved for therapeutic use against a specific type of leukemia, hepatitis B and C, genital warts, AIDS- related Kaposi’s sarcoma and some rare cancers of blood and bone marrow. Nasal sprays containing alpha interferon provide some protection against colds caused by rhinoviruses.

There are two primary types of interferon currently available. To date, interferon-alpha 2a or 2b is the compound that has been extensively used and tested. Though the dose varies, patients with chronic hepatitis C usually receive 3 million units, three times per week. Individuals with chronic hepatitis B receive a higher dose of 10 million units, three times per week. Although it can widely vary, the typical duration of therapy is 48 weeks for hepatitis C, and 16 weeks for hepatitis B.

A newer formulation on the market is called pegylated interferon. This drug was developed in response to the fall in blood levels, rapid breakdown and subsequent loss of antiviral effect of interferon given 3 times per week. By attaching a molecule called polyethylene glycol to interferon-alpha 2a or 2b, researchers were able to slow its breakdown by the body. More consistent drug levels were achieved with the need to only give the drug once per week. Above and beyond the convenience of once a week injection, the pegylated formulations also result in higher viral clearance rates.

Side Effects

Interferon used for hepatitis treatment — alpha and pegylated forms — have been known to cause severe side effects, including:

* worsening of psoriasis
* irritability and insomnia
* trouble breathing
* chest pain
* high fever and chills
* fatigue
* headaches
* decreased appetite, nausea and vomiting
* weight loss
* muscle aches
* bone marrow suppression
* weight and hair loss
* depression and mood changes
* decreased white blood cells and platelets
* elevated liver enzymes
* difficulty concentrating and impaired memory

Interferon’s effectiveness

For hepatitis C, the cure rate is defined as the inability to detect virus in the blood 6 months after stopping therapy. This rate varies significantly depending on a number of patient, viral and drug regimen characteristics. The most important factor is the viral genotype. Unfortunately, genotypes 1a and 1b, the most common types in North America, have the worst response rate, with only 19 percent in interferon and 25-40 percent in pegylated interferon responses, respectively. Adding a second anti-viral drug, ribavirin, increases the response rate to between 35 and 60 percent. Genotypes 2 and 3 carry a much higher eradication rate (60 percent or more).

Hepatitis B is associated with a 35 percent response rate as defined by normalization of liver enzymes and loss of markers of active viral infection. Such a response signifies conversion to a healthy carrier state. This is further characterized by a decrease in the ability to spread the virus to others and a decrease in the liver damage associated with viral infection. Complete elimination of the Hepatitis B virus is rare.

As you can see, not everyone responds to interferon therapy, causing some people to turn to natural alternatives. According to many physicians in Japan, the prescription-strength remedy Sho-saiko-to may be helpful for nonresponders to interferon therapy. If you want more information about Sho-saiko-to, you may wish to visit http://www.shosaikoto.com.

Perhaps having a better understanding of interferon, including what it is, how it works, what its side effects are and how effective it is will help people make the best treatment decisions. Clinical trials are being conducted around the world to increase interferon’s effectiveness, reduce its side effects and create even better alternatives for the eradication of viral hepatitis.

References:

www.aids.about.com, Interferon – alpha, Mark Cichocki, About Inc., 2006.

www.en.wikipedia.org, Interferon, Wikipedia Foundation, Inc., 2006.

www.gihealth.com, Interferon Therapy, Three Rivers Endoscopy Center, 2005.

www.hepatitis-c.de, What is Interferon?, Deutsches Hepatitis C Forum, 2006.

www.immunityfacts.com, Interferon and Its Role in Immune Health, Center for Immune Research, 2006.

www.introna.com, What are Interferons?, Schering Corporation, 2002.

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July 28, 2006

Hepatitis C and the Immune System

Australian researchers have uncovered a link between hepatitis C infection and an individual's immune system. By examining this virus on a genetic level, new understanding about hepatitis C's ability to mutate and persevere in certain people brings us closer to the development of a successful vaccine.

WA leads bid for hep-C cure
by Louise Pemble
July 22, 2006 11:27am

PERTH researchers are closer to explaining why some people can fight off the Hepatitis C virus while others succumb to the potentially deadly infection.

Their findings could pave the way for a vaccine against hepatitis C infection, which affects more than 210,000 Australians and 200 million people worldwide.

The team, based at the Centre for Clinical Immunology and Biomedical Statistics at Royal Perth Hospital, already has made headway in understanding the interplay between the individual and the virus at the genetic level, and how this influences the body's immune response to the virus.

This followed groundbreaking work headed by the centre's director, Simon Mallal, whose study of Perth HIV sufferers was the first in the world to show that patients had different forms of the virus as it tailored itself to individual immune responses and different populations.

Prof Mallal was awarded a $US9.8 million grant by the Bill and Melinda Gates Foundation to create state-of-the-art databases recording the genetics of the virus and people in key populations around the world.

Prof Mallal said it was on the back of those findings that he shifted attention to hepatitis C because the jlbehaviour of the virus was poorly understood, even though it affected so many Australians.

His team worked on a hunch that hepatitis C would behave in the same way as the HIV virus, which constantly mutated to evade a knockout blow by the body's natural defence, the immune system.

Researcher Silvana Gaudieri said the HIV research had been crucial in laying the groundwork for the hepatitis C study, though there were key differences.

"Unlike HIV, of those individuals exposed to hepatitis C, about 30 per cent resolve their infection without the need for therapy," she said.

"For those who become chronically infected, many suffer liver disease, including cirrhosis, and require liver transplants.

"In essence, the hepatitis C epidemic is a time bomb within the community, with a likely high burden on the health system in the years to come."

The research team has just recruited new subjects who are ideal candidates for answering many of the puzzles surrounding hepatitis C.

With funding from the Haemophilia Foundation of Australia, a study now involves West Australians with haemophilia, who will provide a unique nts cohort nte opportunity for discoveries in this area. Many people with haemophilia were exposed to the virus through blood donation before widespread screening was introduced.

Throughout the '70s and '80s, they were given multiple infusions of blood, including plasma infected with hepatitis C, but not all succumbed to the virus.

This made them ideal candidates for study because they had been exposed to many different strains of the virus over time, according to trial investigator Michaela Lucas.

Dr Lucas, working in collaboration with colleagues from the Haemophilia Centre of WA headed by Associate Professor Ross Baker and from CCIBS including Dr Katja Pfafferott, said they offered a rare opportunity to find out why some resolved infection while others did not.

"Work published on HIV showed that an individual's ability to fight the virus leaves an imprint on the virus," she said.

"That's why the virus is always changing to try to evade the body's immune response.

"We were looking for information about how the hepatitis C virus interacts with an individual to resolve why the progress of the disease can differ markedly in each person."

The team is faced with many unsolved questions about hepatitis C. For instance, some people can be infected with hepatitis C for 10 to 20 years with few or no clinical symptoms, while others get liver disease quite rapidly.

Some of the factors that influence the disease's progress are sex, age, alcohol consumption and the presence of another infection, such as HIV.

Researchers turned their attention to which parts of the virus could change to escape or "hide" from the body's immune response.

Two factors were crucial - the way the body fought the virus and the type of virus.

The study focuses on the immune system's specialised white blood cells, or T-cells, that are the key to fighting the virus.

As with HIV, a better understanding of how the virus changes as it moves through a population will help develop designs for vaccines, though Dr Lucas stressed that this was early stage research, rather than a vaccine trial.

Hepatitis C is potentially curable, but many patients do not respond to treatment.

Dr Lucas, who has previously worked with leading hepatitis C researcher Dr Paul Klenerman at Oxford University, said the Perth findings would help explain the role mutation of the virus played in escaping an individual's immune response.

The study, which is now in its second year, has also been supported by the National Health and Medical Research Council and from this month, funding will be added by the Haemophilia Foundation to specifically investigate a person's immune response to multiple strains of HCV.

copyright 2006 The Sunday Times, News Limited

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July 17, 2006

New Component Improves HCV Combination Therapy Results

By replacing ribavarin with anti-cholesterol medications, researchers of a recent study improved the effectiveness of combination therapy in preventing the replication of the hepatitis C virus. This is welcome news, particularly to the 45% of chronic hepatitis C patients who do not respond to current combination therapy.

Statins stop hepatitis C virus from replicating
Source: John Wiley & Sons, Inc.
Contact: Amy Molnar
July 6, 2006

A new study shows that statins, which are typically used as anti-cholesterol medications, can inhibit the replication of the hepatitis C virus (HCV). They could replace ribavirin in combination therapy with interferon.

These findings are published in the July 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).

Currently, 170 million people worldwide are infected with HCV. The standard treatment is a combination therapy of interferon and ribavirin, which is only effective in about 55 percent of patients. The remaining 45 percent face a threat of the disease progressing to cirrhosis and liver cancer. Based on recent reports that one statin, lovastatin, inhibits HCV replication, researchers led by Masanori Ikeda of Okayama University in Japan, tested other statins in search of a more effective anti-HCV therapy.

Using the OR6 cell culture assay system, they evaluated the anti-HCV activities of five statins: atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin. When the statins were tested alone, all except pravastatin inhibited HCV replication. Fluvastatin had the strongest effect. Atorvastatin and simvastatin had moderate effects while lovastatin had a weak effect. While pravastatin exhibited no anti-HCV activity, it did work as an inhibitor for HMG-CoA reductase, suggesting that the anti-HCV activities of the other stains are not due to the direct inhibition of HMG-CoA.

The researchers determined that the anti-HCV activities of statins were not related to cytotoxicity, meaning they did not kill the host cell. Additional experiments also suggested that, "the statins possess the ability to inhibit the replication of HCV RNA via a specific antiviral mechanism," the authors report.

The researchers tested the theory that certain proteins are required for HCV RNA replication and that statins block the replication by inhibiting those proteins. In support of this theory, they found that the addition of both mevalonate and geranylgeraniol restored HCV RNA replication in the statin-treated cells.

To evaluate statins as potential replacements for ribavirin in combination therapy, the researchers tested the anti-HCV activities of each one when combined with interferon. Each combination, except the one including pravastatin, had even stronger inhibitory effects on HCV RNA replication than when the statin was used alone. Again, fluvastatin plus interferon exhibited the strongest effect. "We clearly demonstrated that co-treatment of interferon and fluvastatin was an overwhelmingly effective treatment," the authors report. This combined therapy was more effective against HCV RNA replication than interferon alone and more effective than the standard combination therapy of interferon and ribavirin.

"Statins are good reagents for combination therapy with interferon in patients with chronic hepatitis C," the authors conclude. "Furthermore, our developed OR6 assay system will be useful for the time-saving screening of new anti-HCV reagents."

The journal Hepatology is published by John Wiley & Sons, Inc.

REFERENCE:
"Different Anti-HCV Profiles of Statins and Their Potential for Combination Therapy with Interferon," Masanori Ikeda, Ken-ichi Abe, Masashi Yamada, Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato, Hepatology; July 2006; (DOI: 10.1002/hep.21232).

SOURCE: John Wiley & Sons, Inc., Wiley Interscience.

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