The goal of HCV treatment is to cure the virus, which can be done by using a combination of drugs. The standard of care and duration of treatment for hepatitis C depends on the HCV genotype (or genetic structure of the virus), along with what happens during the initial months of therapy.
Hepatitis C genotype 1 is treated with three drugs: pegylated interferon, ribavirin, and a protease inhibitor. Treatment can last for as long 48 weeks, and will results in a sustained virologic response (SVR) in up to 70 percent of people who have never been treated for HCV.
Genotypes 2 and 3 are treated with pegylated interferon and ribavirin (standard dose is 800 mg/day, but weight based dosing is also used in some cases). Duration of treatment ranges from three to 12 months, depending on hepatitis C viral load, liver damage, insulin resistance, and early response to treatment. Most people are treated for six months because the risk for relapse is greater when treatment is shortened. SVR rates among first-time treatment takers can be over 90 percent for genotype 2, and are 65 percent or more in HCV genotype 3.
HCV genotype 4 is treated with 48 weeks of pegylated interferon and weight-based ribavirin; SVR rates in people living with HCV being treated for the first time are as high as 70 percent.
Here's more specific information on each of these important classes of HCV treatments:
Pegylated interferon. Interferon is a protein made by the immune system, 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, called pegylated interferon. There are two brands of pegylated interferon, Merck’s PegIntron, which is dosed according to weight, and Genentech’s Pegasys, which is given at a fixed dose (i.e., the same dose for everybody).
During HCV treatment, pegylated interferon is given by weekly injections, for up to 12 months, at a much higher dose than what the body produces, 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 (e.g., depression, irritability, insomnia, moodiness). The good news is that clinicians have had years of experience with side effects management.
Ribavirin: Ribavirin is a nucleoside analog. 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 plays an important role in HCV combination treatment. Although scientists have not discovered exactly how it works, it is clear that adding ribavirin boosts cure rates and reduces the risk of relapse.
The major side effect of ribavirin is anemia, which is dose-dependent and can be managed with 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 pregnant or breastfeeding women and their male partners. Men and women who are having intercourse must use birth control during HCV treatment, and for the next six months afterwards, since ribavirin can remain in the bloodstream after people stop taking it.
Protease inhibitors: Two hepatitis C protease inhibitors, Merck’s Victrelis (boceprevir) and Vertex’s Incivek (telaprevir), have been approved to treat hepatitis C, genotype 1, in combination with pegylated interferon and ribavirin. These oral antiviral drugs are used three times per day, for 12 to 44 weeks.
Protease inhibitors block an important step in HCV replication. 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.
Side effects of HCV protease inhibitors may vary according to the particular drug. Both cause anemia. Victrelis may also worsen neutropenia and thrombocytopenia, and causes 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 it will remain that way throughout treatment, and for six months afterwards: an SVR.
Researchers are trying to cure HCV without pegylated interferon, by using a combination of oral drugs, called direct acting antivirals (DAAs) to suppress viral replication, a strategy that works for treating—but not curing—HIV.
Early evidence of the possibility of curing HCV without pegylated interferon and ribavirin was reported at a conference in April 2011, when four of ten people were cured after six months of treatment with two DAAs. Clinical trials are exploring drug combinations and treatment strategies to increase SVR rates, with and without pegylated interferon and ribavirin.
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