The goal of treatment for chronic hepatitis C is to eliminate the hepatitis C (HCV) virus from the body permanently. This is measured by evaluating blood for the presence of the virus after treatment has finished. If no virus is detected, patients have achieved sustained viral response (SVR) and are presumed to be cured. Current guidelines indicate the earliest interval for SVR testing is three months following therapy completion. The specific treatment regimen typically includes multiple medications and is determined by a patient’s genotype (or viral strain) and previous treatment history, as well as the degree of liver damage.
Traditionally, hepatitis C was treated with a combination of injectable interferon and oral ribavirin for extended periods of time (6 – 18 months).
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 body’s natural protein) is given by weekly injections, for several months. These increased concentrations of interferon in the body (naturally occurring + the injected manmade product) not only boost the body’s ability to fight HCV but they can produce various adverse effects. These include flu-like 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 the building blocks of DNA—or the genetic material of most organisms. 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 when used in combination with other hepatitis C treatments. 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: A Revolution in HCV Care
In 2011, a new class of medications (oral protease inhibitors) was approved for patients with genotype 1hepatitis C. These drugs dramatically increased the rate of SVR — or viral cure — when compared to previously available options. Since that time, a number of additional oral medications with various mechanisms of action (the way they fight HCV inside the body) have been approved for all genotypes.
Each of these treatment innovations brought additional benefits to HCV treatment; improving cure rates and tolerability as well as shortening the length of therapy. One thing has remained the same though, the need for multiple medications to effectively cure the HCV virus. As a result, none of these new medications work when used alone. They must be combined with other types of HCV medication (either individually or as part of a combination pill formulation) to achieve the best result.
These new medications are generally referred to as direct-acting antivirals (DAA), meaning these drugs work directly on the virus to stop the growth of HCV. Within this direct acting-antiviral class, the drugs can be subdivided by the way they work against HCV (or their mechanism of action). The principle of combination therapy works by using medications from differing classes in order to attack the virus from many directions, quickly stopping viral growth and preventing opportunities for resistance.
Protease inhibitors block an important step in hepatitis C viral growth. In order to grow, the virus has to be cut—or cleaved—into smaller pieces for processing, copying and reassembly into new virus particles. 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 treat HCV by preventing growth of the virus. In order for the hepatitis C virus 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 manage the assembly of our body’s genetic material, or DNA. When a cell becomes infected with HCV, the virus hijacks this enzyme and uses it to start copying hepatitis C instead. Polymerase inhibitors work by blocking the use of this 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.
NS5A inhibitors target a specific protein (named NS5A) within the hepatitis C virus. This protein is an important player in the growth and assembly of the virus. The NS5A protein is one of the key mediators of the hepatitis C life cycle. NS5A inhibitors block the functions of this protein and help lower the amount of virus in the liver cells. NS5A inhibitors are considered one of the most potent anti-viral molecules.
While side effects can vary, the most common side effects seen with the NS5A inhibitors are nausea, headache and fatigue.
Combination, Direct-Acting Antivirals
Newer products, such as Harvoni®, Technivie®, Viekira Pak® and ZepatierTM combine multiple medications with varying mechanisms of action to increase treatment efficacy and reduce the risk of HCV resistance. These combination products offer short-course treatment lengths similar to other oral HCV medications. Not only does this combination product approach provide effective treatment, but it also adds convenient, fixed-dose regimens with as few pills as possible to make complying with HCV treatment even easier.
Similar to the newer single-product antivirals, side effects of these combination therapies are considerably less intense as compared to traditional interferon-based HCV treatment. Side effects vary between the medications but can include symptoms such as nausea, headache or fatigue.
Newer regimens are not only highly effective and convenient but they are also typically well tolerated. No matter which regimen is utilized, follow-up monitoring including laboratory is an essential part of individualizing HCV therapy and optimizing treatment outcomes.
Medication Adherence, an Essential Ingredient to Treatment Success
No matter which treatment regimen you plan to use, taking your medication exactly as prescribed is one of the most important things you can do. Missing doses of medication –or skipping part of your prescribed combination regimen—allows the hepatitis C virus time to multiply and may even allow resistant virus to occur. Taking medications on a regular schedule and using adherence tools, such as the Accredo Plus C app (available free in the Google Play or App store), can help keep you on track.
New Treatments on the Horizon
Scientists continue to work to find more effective, tolerable and shorter course HCV treatment options. Researchers are particularly focused on developing combination products (where multiple medications are combined in one pill) to improve ease of use for the patient. Numerous regimens are under study. One example of an all-oral, interferon-free treatment in the late stages of clinical investigation:
- Velpatasvir/ sofosbuvir (Gilead)
- Co-formulation of a NS5A inhibitor, velpatasvir and the polymerase inhibitor sofosbuvir
- Once daily medication with activity in genotypes 1-6