How Hep C Treatment Has Gotten So Much Better Over the Years

by Erin L. Boyle Health Writer

It's 100% true that until about five years ago, Hepatitis C (HCV) treatment was pretty awful. It was long. It made you feel really sick. And it didn’t even work that well. And because those stories are still in the very recent past, there’s still a lot of misinformation out there about side effects, and some people are reluctant to get treatment that can be lifesaving. We’re going to help put some of that history in context and most importantly, show you how much things have changed when it comes to treating (and curing) Hep C. First, we go back (way back).

Early Days of HCV Treatment Were Rough

So here’s a little historical context. Until 1989, HCV wasn’t considered a specific infection—it was called non-A and non-B hepatitis (NANBH)—meaning it wasn’t the types of hepatitis that were known. In 1991, interferon was approved for use in treating NANBH, along with ribavirin. These drugs were at least something, but not exactly great options. They caused flu-like symptoms, fatigue, muscle aches, anemia, insomnia, and nausea, and even at their peak effectiveness, were still only curing about 40-50% of people.

woman taking pill that looks like Victrelis

The Breakthrough: Direct-Acting Antivirals

In 2011, Incivek (telaprevir) and Victrelis (boceprevir) were approved as direct-acting antiviral (DAA) agents. Unfortunately, they introduced more side effects, including rashes and nausea, making HCV treatment go from bad to worse, says Douglas Dieterich, M.D., professor of medicine and director of outpatient hepatology at the Icahn School of Medicine, Mount Sinai Health System in New York. Alternative DAA medications with fewer side effects and better success rates were soon developed, and a handful were approved between 2014 and 2017. “It happened faster than anyone anticipated,” Dr. Dieterich notes.

tired man on bench

New Hep C Drugs Have Fewer Side Effects

In 2014, researchers conducting a study of HCV patients treated with a new drug, Harvoni (ledipasvir/sofosbuvir), found fatigue, headache, and nausea were the most common side effects: Not perfect, but way better than a rash and the flu! In addition, they found that patients had higher adverse reactions when ribavirin (the drug traditionally used in conjunction with HCV treatment) was added to their DAA treatment. Researchers looked at Harvoni alone at 8 weeks versus Harvoni combined with ribavirin. A total of 21% of patients with just Harvoni experienced fatigue; 35% with ribavirin added felt tired, indicating its adverse effects.

Today's DAAs Are More Effective

DAAs achieve sustained virologic response (SVR), a.k.a. a cure, in nearly all HCV patients, according to K.V. Narayanan Menon, M.D., a gastroenterologist, hepatologist, and medical director of liver transplantation at Cleveland Clinic.

That's a world of difference from when he started practicing medicine 20 years when response rates were about 10%, says Dr. Menon. “Slowly it went up to about 20-25% [with interferon/ribavirin], then in the late 2000s, it rose to about 50% [with first-generation DAAs added]," he says. "Now, we are at a 99% cure rate” with the most recent DAAs.

DAAs Don’t Act the Same Way as Older Meds

The likely reason interferon and ribavirin had more side effects and less effectiveness? These drugs don’t kill HCV, but instead stimulate the immune system to attack it. The constant immune response triggers flu-like symptoms throughout treatment. (“One of my patients said it was like 12 months of PMS with a cold,” says Dr. Dieterich.) DAAs, or direct-acting antivirals, attack the virus itself by targeting HCV-encoded proteins key to the virus’ replication, effectively stopping it in its tracks. Once the infection is addressed, the liver has a chance to heal and regenerate.

Older Meds Had Mental Health Side Effects

One serious drawback of older treatments: An increased risk for depression. Its prevalence ranged from 30-70% in HCV patients receiving early types of treatments, who also were at risk for psychosis, suicidal ideation, and suicide attempts. The correlation could have something to do with interferon’s role as an immune mediator, causing changes in enzymatic pathways involved in producing feel-good chemicals like serotonin, dopamine, and norepinephrine. People receiving interferon/ribavirin were often screened for mental health conditions before and during treatment, says Jennifer Eames, P.A.-C, director of the Physician Assistant Program at Hardin-Simmons University in Abilene, TX.

Now: DAAs Offer Real Hope to Patients

Some people with HCV have zero symptoms, but many others experience fatigue, nausea, and flu-like conditions that never seem to end. For Bill Remak, 66, of Petaluma, CA, HCV symptoms were a way of life. Diagnosed with chronic persistent hepatitis in 1966, he's endured liver cancer, two liver transplants, and six years of failed interferon/ribavirin treatments. By the time he went on a new DAA in 2016, he didn’t know what to expect. He was cured of HCV that year. “I’ve been able to see my kids get married and have grandchildren,” Remak says. “These are things I would have not experienced. How can you even put value to that? It’s an incredible development.”

Now: DAAs Have a Shorter Treatment Time

Another big difference between interferon/ribavirin treatment and newer DAAs: The duration. With interferon, you might have to take it for up to a year; with DAAs, you generally take them for just eight to 12 weeks. The lengthy stint on earlier types of drugs could be responsible for complications: In 2001, Karen Hoyt, 62, of Tulsa, OK, underwent HCV treatment with interferon, ribavirin, and a now-discontinued protease inhibitor. She was supposed to be on medication for 48 weeks, but at week 44, an esophageal bleed-out landed her in intensive care. “My doctor had to discontinue treatment, but thankfully I had been cured,” she says.

Pill Box And Medication Sitting On Top Of A Bedside Nightstand

You’re More Likely to See Treatment Through

With such awful side effects and mediocre results, it was hard for many HCV patients to keep taking older drugs for the prescribed duration. Some patients, like Hoyt, had to be taken off treatment for their own safety. Now, with faster results and less-debilitating side effects, HCV patients are much more likely to finish their course of treatment, Dr. Menon notes. Which is important because the body can become resistant to DAAs once treatment is stopped, meaning the meds won’t work as they should once treatment resumes. Plus, they’re expensive, and a second course might be tough to have approved by health insurance if it's requested simply because the patient stopped taking them.

Syringe and Pills

Current Hep C Meds Are Easier to Take

With today's DAAs, you'll likely take one pill (or, in one treatment regime, three pills) once a day, for two to three months. That's a pretty good deal compared to earlier medications like interferon, which required patients to inject themselves with the drug three times a week during the course of their treatment. (Those patients also needed to remember to take their oral ribavirin and later, protease inhibitors, too.) Hoyt appreciates the ease of newer medications. She had to take pills every eight hours, plus a weekly interferon injection, for nearly a year. Between doses and side effects, she says, “I was like a zombie.”

Bottom Line: No Drug Is Perfect

While newer DAAs have far fewer side effects than older meds, they do have some. If you’re being treated for HCV and feel extra-tired, have headaches you can’t shake, or frequently feel nauseous, let your doctor know, says Eames.

“Communicate with your physician and healthcare team when you experience side effects and plan ahead in case you do,” agrees Connie Welch, 61, of Keller, TX. Keller, who was cured of HCV in 2012, points out that the treatment length is much more bearable now. If you experienced treatment failure before and are hesitating to try again, look at it this way: You're trading eight to 12 weeks of possible discomfort for a lifetime free of HCV. Sounds like a pretty good deal!

  • HCV Becomes a Diagnosis: Mini-Reviews in Medicinal Chemistry. (2018). “Recent Advancement of Direct-acting Antiviral Agents (DAAs) in Hepatitis C Therapy,”

  • Interferon’s Early Days: Hepatitis Research and Treatment. (2010). “Treatment of Hepatitis C Infections with Interferon: A Historical Perspective,”

  • Newer DAAs Enter the Scene: Gastroenterology & Hepatology. “New Therapies for Hepatitis C Virus Infection,”

  • First-Generation Protease Inhibitors Discontinued: GoodRx. (2015). Victrelis: Another Hepatitis C Medication Discontinued.

  • New Hep C treatments have Few to No Serious Side Effects: The New England Journal of Medicine. (2014) “Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis,”

  • DAAs Don’t Act the Same Way as Older Meds: UpToDate. (2019). “Direct-acting antivirals for the treatment of hepatitis C virus infection,”

  • DAAs have Fewer Mental Health Side Effects. Annals of Gastroenterology. (2015). “Depression and suicide ideation in chronic hepatitis C patients untreated and treated with interferon: prevalence, prevention, and treatment,”

Erin L. Boyle
Meet Our Writer
Erin L. Boyle

Erin L. Boyle, the senior editor at HealthCentral from 2016-2018, is an award-winning freelance medical writer and editor with more than 15 years’ experience. She’s traveled the world for a decade to bring the latest in medical research to doctors. Health writing is also personal for her: she has several autoimmune diseases and migraines with aura, which she writes about for HealthCentral. Learn more about her at Follow her on Twitter @ErinLBoyle.