Hepatitis C: The Basics : What treatments are available?
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Lesson Hepatitis C: The Basics


What treatments are available?

The goal of HCV treatment is to cure the virus, which can be done with a combination of drugs. The specific meds used and the duration of treatment depend on a number of factors, including HCV genotype (genetic structure of the virus), past treatment experience, eligibility to take the drug interferon and whether the person is waiting for a liver transplant.

The current standard-of-care for hepatitis C involves taking one of two newly approved therapies, Sovaldi (sofosbuvir) or Olysio (simeprevir), plus ribavirin and in many cases pegylated interferon as well. Although regimens that include Incivek (telaprevir) or Victrelis (boceprevir) plus ribavirin and pegylated interferon are also approved, they are associated with increased side effects and longer duration of treatment and are therefore not considered preferred regimens.

Here are the recommendations for HCV treatment for all genotypes from the American Association for the Study of Liver Diseases (AASLD):

AASLD HCV Treatment Recommendations
for treatment-naive patients who are eligible to receive interferon
Recommended Alternative
Genotype 1 Sovaldi + ribavirin + pegylated interferon for 12 weeks Sovaldi for 12 weeks + ribavirin + pegylated interferon for 24 weeks*
Genotype 2 Sovaldi + ribavirin for 12 weeks none
Genotype 3 Sovaldi + ribavirin for 24 weeks Sovaldi + ribavirin + pegylated interferon for 12 weeks
Genotype 4 Sovaldi + ribavirin + pegylated interferon for 12 weeks Olysio for 12 weeks + ribavirin + pegylated interferon for 24–28 weeks
Genotype 5 or 6 Sovaldi + ribavirin + pegylated interferon for 12 weeks ribavirin + pegylated interferon for 48 weeks

AASLD HCV Treatment Recommendations
for treatment-naive patients who are NOT eligible to receive interferon
Recommended Alternative
Genotype 1 Sovaldi + Olysio + ribavirin for 12 weeks** Sovaldi + ribavirin for 24 weeks***
Genotype 2 Sovaldi + ribavirin for 12 weeks none
Genotype 3 Sovaldi + ribavirin for 24 weeks none
Genotype 4 Sovaldi + ribavirin for 24 weeks none
Genotype 5 or 6 none none

* For people with either HCV genotype 1b or HCV genotype 1a and in whom the Q80K polymorphism is not detected before treatment
** Physicians must prescribe this regimen “off label” because the combination of Solvaldi, Olysio and ribavirin has not been approved by the U.S. Food and Drug Administration (FDA). Research of this drug regimen among those with genotype 1 has been promising
*** Preliminary data suggest this regimen may be less effective than the recommended regimen, particularly among those with cirrhosis

Here's more specific information on the approved hep C treatment options:

Pegylated interferon: Interferon is a protein made by the immune system, so named because it interferes with viral reproduction. In addition, interferon signals the immune system to recognize and respond to microorganisms, including viral and bacterial infections. Infected cells release interferon to trigger the immune response. There are three types of interferon: alfa, beta and gamma. Interferon alfa is used to treat viral hepatitis and some types of cancer.

In the 1980s, researchers were able to create interferon alfa in a laboratory. Hepatitis C is treated with man-made interferon alfa that has a molecule attached to keep it in the body longer and make it more effective; it's called pegylated interferon. There are two brands of pegylated interferon, PegIntron, which is dosed according to weight, and Pegasys, which is given at a fixed dose (in other words, the same dose for everybody).

During HCV treatment in which pegylated interferon is required, the drug is given by weekly injections, at a much higher dose than what the body produces naturally, causing many side effects. These include flu-like symptoms, laboratory abnormalities such as anemia (abnormally low red blood cell count), neutropenia (a decrease in neutrophils, a type of white blood cells that fight bacterial infections) and thrombocytopenia (low platelets), as well as psychiatric problems (such as depression, irritability, insomnia and moodiness). The good news is that clinicians have had years of experience managing side effects.

Ribavirin: Ribavirin is a nucleoside analog, which is a drug that inhibits the hepatitis C virus's ability to replicate. It comes as a pill, capsule or liquid. Ribavirin is taken twice daily, and dosing is based on weight. Although it is not effective against hepatitis C when used alone, ribavirin currently plays an important role in HCV combination treatment. (Up and coming combination therapies have successfully treated study participants without the drug, however.) Scientists have not discovered exactly how it works, but it is clear that adding ribavirin boosts cure rates and reduces the risk of relapse in currently available treatment regimens.

The major side effect of ribavirin is anemia, which is dose-dependent and can be managed by taking red blood cell growth factors or by lowering the dose of ribavirin. Additional side effects include heart problems, depression, dry skin, itching, rash, headache, cough and sinus problems, fatigue, diarrhea, dizziness, appetite loss, nausea and vomiting.

Ribavirin causes birth defects in animals, so it cannot be used by women who are pregnant or by the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy while taking the drug. As a result, men and women who are having intercourse must use two forms of birth control during HCV treatment and for the next six months afterward, since ribavirin can remain in the bloodstream after people stop taking it.

Nucleoside and nucleotide HS5B polymerase inhibitors: These drugs mimic a nucleotide, which the virus would ordinarily use to help copy itself. When the nucleotide analog is substituted for the normal nucleotide, the virus cannot replicate. Sovaldi (sofosbuvir) is taken once a day with ribavirin and often pegylated interferon as well for 12 to 24 weeks, or for up to 48 weeks among those awaiting a liver transplant.

In clinical trials, the most common side effects of Sovaldi when given with ribavirin were fatigue and headache. For those treated with Sovaldi, ribavirin and pegylated interferon-alfa, the most common side effects reported were fatigue, headache, nausea, insomnia and anemia.

NS3/4A protease inhibitors: These drugs also block an important step in the HCV replication process. The hepatitis C virus uses its protease enzyme to cut, or cleave, long strands of virus into shorter pieces, so that they can be rearranged and reassembled to form new viruses. Protease inhibitors stop viral cleavage by binding to the protease enzyme so it cannot cut, similar to covering scissor blades with glue.

One example of protease inhibitors is Olysio (simeprevir), which was recently approved to treat HCV genotype 1 in combination with pegylated interferon and ribavirin. In clinical trials, the most common side effects of Olysio when given with pegylated interferon alfa and ribavirin were rash (including photosensitivity), itching and nausea. There were some cases of photosensitivity reactions warranting hospitalization. Those taking Olysio are advised to limit sun exposure and to protect themselves against the sun during treatment.

Also approved to treat genotype 1 of hepatitis C are Victrelis (boceprevir) and Incivek (telaprevir). Taken in combination with pegylated interferon and ribavirin, these oral antiviral drugs are used three times per day, for 12 to 44 weeks. Regimens with Victrelis and Incivek are associated with increased side effects and longer duration of treatment and are therefore not preferred.

Side effects of Victrelis and Incivek may vary according to the particular drug. Both cause anemia. Victrelis may also worsen neutropenia and thrombocytopenia, and it may cause dysgeusia (metallic or altered taste in the mouth), dry mouth, vomiting and diarrhea. Incivek can cause a mild to serious rash, itching, hemorrhoids, anal and rectal burning, elevations in bilirubin and uric acid, and gastrointestinal discomfort.

When hepatitis C treatment is working, the virus will become undetectable within four to 12 weeks and will remain that way throughout treatment. People are considered cured when they have achieved what is known as a sustained virologic response (SVR), or continuation of this undetectable status, 12 to 24 weeks after completing therapy.

Starting at the end of 2014, newer hep C therapies are likely to come on the market that will make it much easier to cure the disease without the need for interferon, and possibly without ribavirin as well. Phase II and III studies of these combination therapies have been promising and have boasted excellent cure rates-as high as 100 percent in some cases.

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Last Revised: March 12, 2014

This content is written by the Hep editorial team.


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