Treatment

The goal of treatment for hepatitis C is to obtain a sustained virological response (SVR). A viral load test is done to measure the amount of HCV in the blood. If there is no detectable amount of HCV in the blood 6 months after completing a full course of treatment, then SVR has been obtained and the treatment has worked. There are a number of factors that determine SVR. The genotype is particularly important. Those with genotypes 2 or 3 are more likely to respond to treatment with SVR. Those with genotype 1 (the most common in the U.S.) are less likely to have a SVR. Being HIV positive, having a very high HCV viral load, or having cirrhosis of the liver will also hamper SVR.

There are a number of clinical trials currently in progress, and some medications are having positive results. These medications are not yet available outside of trials. The launch of a vaccination for hepatitis C was recently delayed for 3 years. A combination therapy of pegylated interferon and ribavirin are the current treatments of choice for Hepatitis C.


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The goal of HCV anti-viral treatment is sustained virological response (SVR).
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Pegylated interferon

Polyethylene glycol (PEG) is a polymer; a substantially long molecule). PEG is non-toxic and is used as the basis for a number of laxatives (as macrogol) and skin creams (cetomacrogol). Pegylation is adding a PEG structure to another larger molecule, which is then referred to as "pegylated." When various protein medications (such as interferon alpha, which is used to treat hepatitis C) have PEG attached, it provides a longer acting medicinal effect and/or reduces toxicity and allows longer periods between doses.

Ribavirin

Ribavirin belongs to a class of drugs called nucleoside analogues. This drug class includes some anti-HIV drugs like zidovudine (AZT). Ribavirin is not effective used alone for the treatment of Hepatitis C, but works with pegylated interferon. Together, they are more effective preventing HCV from making new copies of itself, and helping the immune system kill HCV. There are two brand-name versions of ribavirin: Copegus and Rebetol. There are also generic versions of ribavirin available, including Ribasphere, that are less expensive and equivalent to the branded drugs. The dosage is usually individualized according to body weight.

Ribavirin must not be used in females who are pregnant, or males whose partners are pregnant, because of toxicity that results in significant teratogenic and/or embryocidal effects, even at very low doses. A negative pregnancy test must be obtained immediately prior to treatment and females of child-bearing potential and males must use 2 forms of birth control during treatment and for 6 months after treatment.


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Ribavirin must not be given to women who are pregnant, and women receiving the drug must use double birth control.

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Combination therapy

Studies have evaluated the effectiveness of pegylated interferon alone or combination pegylated interferon/ribavirin therapy.

Infection
Therapy
Effectives-SVR achieved
Type 1
Type 2 & Type 3
HCV Combination 45-50% 80%
HCV Pegylated Interferon 15% 35%
HCV & HIV Combination 14-29% 44-73%

Treatment guidelines by the American Association for the Study of Liver Diseases recommend that people co-infected with HIV and HCV receive combination treatment for 48 weeks for all genotypes. Some doctors are treating co-infected people with genotype 1 for 72 weeks. People with HCV alone and genotype 2 or 3 are treated for 24 weeks. Viral load should drop significantly after the first 12 weeks of treatment. If this does not occur, many doctors will advise stopping treatment.

Not all groups respond equally to the drugs. For example, the drug interferon is less effective for African Americans. One study showed that only 5% of blacks responded well to interferon, compared with 28% to 40% for other ethnic groups. More ethnic-specific studies need to be conducted to evaluate therapy.

Researchers at Johns Hopkins University evaluated hepatitis C treatment effectiveness from reports published from 1996 through March 2002. They concluded that results consistently showed combination therapy with high dose once weekly injections of pegylated interferon and daily ribavirin was more effective than the standard 3 times a week interferon with daily ribavirin in previously untreated patients. The combination therapy was consistently more effective than "interferon only" treatment, but was still relatively ineffective for those who had failed previous interferon only treatment.


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Vaccinations

Vaccinations are an important adjunct to antiviral therapy:

While there is, as yet, no vaccine for HCV, there are vaccines for HAV and HBV. Individuals with HCV-related liver disease should be vaccinated against HAV because a co-infection would put them at risk of death from liver failure. All individuals with chronic liver disease should be vaccinated against influenza and Pneumococcus. Persons with continued risk factors for HBV infection should be vaccinated. Major routes of transmission of HBV among adults in Western countries are intravenous drug use and sexual contact. The risk of HBV infection is especially high in promiscuous males having sex with males (MSM), but it is also transmitted sexually from men to women and women to men.


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All persons with HCV should be vaccinated for HAV, influenza, and Pneumococcus.

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Liver transplant

Liver transplants are done for end stage liver failure caused by hepatitis C and other disorders. HCV is the most common reason for liver transplantation in adults in the United States, accounting for 30% to 35% of the total transplants. Because of HCV, the number of people needing liver transplants is expected to rise from the current number of about 4000 annually, to over 20,000 over the next 15 to 20 years. While hepatitis C is an infection of the liver, the HCV lives in other cells than the liver and once the liver is replaced by a donor liver, hepatitis spreads back into the new liver within the first weeks to months.

A study at St. Louis University School of Medicine, led by Adrian DiBisceglie, reviewed 107 patients who had liver transplants for a variety of reasons and concluded that HCV patients with a history of alcoholism are candidates for transplantation of the liver:

After 29 months, no significant differences were reported among the different groups in relation to survival of the patient or the donor liver. Overall, 26% of the patients died during follow-up and another 10% required a second liver transplant.

An interesting study by Hugo Vargas, and his associates at the University of Pittsburgh, looked at the effectiveness of using HCV positive livers in HCV-infected patients. HCV is the leading cause for liver transplantation in the United States. Approximately 30% of the 4 million people infected with hepatitis in the United States will eventually need liver transplants, but not enough donor livers are available. Vargas and his team compared 23 HCV-infected patients who received HCV infected livers with 169 HCV infected patients who received healthy livers and found comparable 1 and 5 year survival rates. One group of patients received donated livers infected with a different strain of HCV than the one they carried, and this group remained disease free for significantly longer than others who received infected and healthy livers. The researchers believed that the donor strain prevailed over the patient's strain and extended the disease-free interval. While most infected livers are now discarded, this study shows that they are a viable solution to the shortage of healthy livers for those already infected with HCV.


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Contraindications for treatment

Treatment is contraindicated in some patients:


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