The goal of treatment for chronic hepatitis C is to eliminate the HCV virus from the body permanently. This is measured by evaluating blood for the presence of the virus six months after treatment has finished. If no virus is detected, patients have achieved sustained viral response (SVR) and are presumed to be cured. The specific treatment regimen is determined by a patient’s genotype and previous treatment history as well as the degree of liver damage. It often includes several medications.
Traditionally, HCV was treated with a combination of interferon and ribavirin. In 2011, two new medications (oral protease inhibitors) were approved for patients with genotype 1. These drugs dramatically increased the rate of SVR—or viral cure—when compared to previously available options. To achieve maximum efficacy they are prescribed in combination with other medications, typically interferon and ribavirin, creating a triple therapy regimen.
Interferon is a protein made by the immune system which interferes with viral reproduction and boosts the body’s natural response to disease. During HCV treatment, pegylated interferon (a manmade version of the natural protein) is given by weekly injections, for up to 12 months. These increased concentrations of interferon in the body (naturally occurring + the injected manmade product) can produce various adverse effects. These include flu-like s symptoms, low blood cells, as well as psychiatric problems (e.g. depression, irritability, insomnia, moodiness). The good news is that clinicians have years of experience with side effect management and many strategies are available to help improve tolerance to this therapy.
Ribavirin is a molecule that mimics some of the building blocks of DNA. It is administered orally and is typically taken twice daily in a dose based on weight. Although it is not effective against hepatitis C when used alone, ribavirin plays an important role in HCV combination treatment. While scientists have not discovered exactly how it works, it is clear that adding ribavirin boosts cure rates and reduces the risk of HCV relapse.
The major side effect of ribavirin is anemia, or low red blood cells. Ribavirin also causes severe birth defects, so it cannot be used by pregnant or breastfeeding women or by their male partners. Birth control for both male and female patients taking ribavirin is essential while on therapy and for six months after treatment ends.
Oral viral inhibitors
Investigators have been working hard looking for new treatments to improve the rate of viral cure. Goals of these efforts also include providing effective treatment options for all genotypes and those with more advanced disease, all while ensuring regimens can be administered orally, are shorter in duration and interferon free.
This class of new antivirals is generally referred to as direct-acting antivirals. Meaning these drugs work directly on the virus to stop the growth of HCV. Within this class the drugs can be subdivided by the way they work against HCV (or their mechanism of action). Some examples include the following:
Olysio (simeprevir), Incivek (Telaprevir) and Victrelis (Boceprevir)
Protease inhibitors block an important step in HCV replication (or growth). In order to grow, the virus has to be cut into smaller pieces for processing, copying and reassembly. Protease inhibitors stop this 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 vary according to the particular drug but some possible symptoms include low blood cells, rash, itching and upset stomach.
Polymerase inhibitors also work by blocking viral replication (or growth). In order for HCV to continue growing and infecting new cells, the virus must first make new copies of itself. Polymerase is a naturally occurring enzyme in human cells whose job is to assemble the building blocks of DNA and RNA. When a cell becomes infected with HCV, the virus hijacks this enzyme and uses it to start the HCV viral copying process instead. Polymerase inhibitors work by blocking the enzyme and preventing the creation of new virus particles and the spread of HCV to healthy cells.
Side effects of HCV polymerase inhibitors may vary but some possible symptoms include headache and fatigue.
New viral inhibitors and combination products on the horizon:
Scientists continue to work to find more effective, more tolerable and shorter HCV treatment options. There are many products on the horizon. Some medications in the late stages of clinical investigation include:
- Ledipasvir - a replication complex inhibitor: FDA approval expected soon for use in combination with Sovaldi
- ABT-450/ABT-267/ABT-333 - a combination regimen including a protease inhibitor, polymerase inhibitor and a replication complex inhibitor