Understanding Hepatitis C Therapy

Direct Acting Antivirals Achieve High Cure Rates in Chronic Infection

Doctor with Patient
Doctor with Patient. Adam Berry / Stringer / Getty Images

If infected with the hepatitis C virus (HCV), one of two things would happen. You would develop an acute infection, either symptomatic or asymptomatic, which your immune system would either be able to clear from your body; or the virus would persist to become what is known as a chronic infection.

Typically, between 20% and 30% of HCV infection are spontaneously cleared with no drug intervention. Of the remaining 70% to 80%, the disease could progress over the course of decades and gradually damage the liver, resulting in cirrhosis, liver cancer, or liver failure in about 30% of those cases.

Hepatitis C treatments today have been shown to be highly effective in effectively "curing" the disease, with newer generation drugs now able to treat even patients with cirrhosis who have failed previous therapies.

The Basic of Hepatitis C Therapy

The goal of hepatitis C treatment is to suppress the virus to the point where it becomes undetectable in blood tests and remains undetectable. Doctors define this is a sustained virologic response (SVR).

Research has shown that chronically infected persons who are able to maintain an SVR for 24 weeks following HCV therapy have only a 1% to 2% chance of rebounding (i.e., experiencing a return of virus). As such, an SVR-24, as it is called, can reasonably classified as a "cure."

Even in patients who are not able to achieve SVR-24, the benefits of partial response can be enormous, slowing disease progression and reversing some of the liver scarring (fibrosis) associated with infection.

By doing so, patients have time to consider other drugs options, and to decide if and when they want to be re-treated.

Peginterferon and Ribavirin

Prior the introduction of newer generation HCV drugs in 2013, doctors had to rely on two drugs, peginterferon, and ribavirin, as the standard treatment for chronic hepatitis C infection.

The combination of these two agents, while not perfect, managed to achieve SVR-24 in about half of all treated patients. But they often did so with high levels of side effects, as well as high rates of termination due to drug intolerability.

Among the common side effects of peginterferon/ribavirin therapy:

  • Anemia
  • Headache
  • Irritability and anxiety
  • Depression and suicidal ideation
  • Hair loss (alopecia)
  • Itchiness
  • Insomnia)
  • Joint pain (arthralgia)
  • Muscle pain (myalgia)
  • Anorexia
  • Nausea and vomiting
  • Fever
  • Chills
  • Fatigue
  • Insomnia
  • Nausea and vomiting
  • Skin rashes
  • Extreme tiredness

While newer generation therapies tend to avoid peginterferon and ribavirin, the drugs are still considered important for patients with advanced disease, including cirrhosis, or those with previously failed therapy. Some of these newer therapies only require ribavirin, for instance, with far shorter treatment duration.

Direct Acting Antivirals (DAAs)

It was in 2014 that the market introduction of Sovaldi (sofosbuvir) ushered in a new era of hepatitis C therapy, offering cure rates that had, up until that time, been unheard of. Within the span of the next two years, other drugs classified as direct acting antivirals (DAAs) were quickly approved for use by the U.S. Food and Drug Administration (FDA), including the first all-in-one, single-pill DAA, Harvoni (sofosbuvir + ledipasvir).

This new class of drug not only achieved cure rates of up to 99%, they did so with treatment duration of as short as 12 weeks and with minimal and mostly transient side effects. They were also able to treat an increasing number of HCV genetic strains (called genotypes), some of which were considered very hard to treat.

As a result, a number of older agents (Incivek, Victrelis) were voluntarily retired by the manufacturers, unable to compete with either efficacy or market demand.

The following DAAs have been approved by the FDA for the treatment of chronic hepatitis C:


Rockstruh, J. "Summary from EASL 2015 for Hepatitis C All oral HCV DAA therapy on its way to optimization: still much to learn." 50th Meeting of the European Association for the Study of the Liver (EASL). April 22-26, 2015; Vienna, Austria.

U.S. Food and Drug Administration. "Merck Voluntarily Discontinuing VICTRELIS (boceprevir) 200 mg Capsules." Released January 2015.

Boston Globe. "Vertex to stop selling hepatitis C drug Incivek." Published August 12, 2014.