Hope for Hepatitis C

WHEN SPEAKING with Sue Simon, it is difficult to believe she was ever ill or even discouraged. After her stage-4 hepatitis C diagnosis in 1991, the upbeat elementary school teacher faced two decades of painful, unsuccessful treatments. “I tried every interferon that came on the market,” she says. “Every time a pharmaceutical company changed or tweaked a drug, I tried it.”

Despite her willingness and efforts to battle the hepatitis C virus (HCV), some treatments left her even sicker. “For two years I tried maintenance treatment with interferon. It destroyed my bone marrow,” she explains. “I was in the hospital for almost the whole summer in 2008 because it suppressed my immune system and I had no white count at all.”

Still, she fought to beat the virus. Finally, in 2013, a clinical trial of the direct-acting antiviral drug Viekira Pak (ombitasvir/paritaprevir/ritonavir; dasabuvir) cured her. Sue will be HCV-free for the rest of her life. She never dreamed she would see the day when a virus is cured with medication, but she is now adamant about others getting tested and finding help along their own HCV journey. She has also discovered another calling as a patient advocate/writer for the HCV community. “Get tested, get treated, get cured” is her confident advice to those who have not previously considered hepatitis C but may be at risk.

Historically, such assurance has not been as available to hepatitis C patients. Optimism is, in fact, a very recent development in this virus’s story.

History, Background and Epidemiology

Once called non-A or non-B hepatitis because it did not share the same serological markers of the better-known hepatitis A or hepatitis B,¹ the virus that is now known as hepatitis C was identified in 1989. Scientists suspect it existed for decades before that.^2,3

“HCV belongs to a family of viruses called flaviviruses, which include the causative agents of yellow fever, dengue fever and West Nile encephalitis,” explains Dr. Ira Jacobson, chairman of the department of medicine at Mount Sinai Beth Israel and vice chair of the department of medicine at Icahn School of Medicine at Mount Sinai. “It’s spread by parenteral transmission, which means it’s not spread orally, but rather requires percutaneous exposure to body fluids that contain the virus. The most common routes of transmission are, by far, exposure to contaminated blood, which is why thousands and thousands of people used to get it from blood transfusions. That was before the advent of highly accurate HCV tests developed in the early 1990s to screen blood donors. The virus is also transmitted readily among drug users who share syringes or other equipment. Perhaps about 3 to 5 percent of the time, it can be passed by mother to infant though vertical transmission. And, though it is rare in the United States, the virus has been spread on a large scale through nosocomial transmission, which is infection from a healthcare setting through unhygienic equipment. Doctors are mystified by the small percent of patients who get hepatitis C yet are without any of these risk factors.”

Dr. Ype de Jong, assistant professor at Weill Cornell Medical College and a visiting assistant professor at The Rockefeller University, agrees that some cases are mysterious: “I have patients who really cannot find another risk factor other than just getting manicures [from a salon with suspected contaminated equipment]. So I think there is still some low-level infection here and there. Sometimes people get it from contaminated endoscopy equipment, but these are the stories that make the national news in this country.”

The medical community is most concerned about IV drug users. “The heroin epidemic that is ongoing, mostly because we doctors have been prescribing opiates like crazy in this country, has created an iatrogenic opiate addiction,” explains Dr. de Jong. “Heroin and other IV drugs are so much less expensive than opiates that there is now an enormous amount of heroin use in rural America, particularly in the rural Northeast. The Centers for Disease Control and Prevention [CDC] is afraid that these people are sharing needles, and there has been an uptick in the prevalence of hepatitis C in 2013.”4

Even if a person has no dramatic risk factors such as drug use, everyone in the HCV community stresses the importance of being tested. “One of the biggest things is birth cohort screening — or screening according to one’s birth year,” explains Dr. de Jong. “There was so much drug use in the 1960s and ’70s, and then injuries in Vietnam that required transfusions, that the baby boomer generation — those born between 1945 and 1965 — should be tested for hepatitis C. They believe 5 percent of the people have hepatitis C even if they’re asymptomatic and have no risk factors. Everyone should still get screened.”

Dr. Jacobson adds that in some areas, testing is statutory: “It is now mandatory in some states, including New York, that people born between the years 1945 and 1965 have a one-time test for hepatitis C in certain contexts, such as primary care offices or upon admission to a hospital. You’re automatically supposed to have a test for hepatitis C if you haven’t had one before. That’s because up to two-thirds of people with hepatitis C in this country are baby boomers. And so it was decided by agencies like the CDC and the U.S. Preventive Services Task Force that an efficient way to identify the majority of as-yet undiagnosed Americans would be via birth cohort rather than risk-based screening.”

Symptoms and Diagnosis

“Diagnosis almost always is a shock to patients,” says Dr. Raymond Chung, director of hepatology at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School. “Of the three million patients in the United States who have hepatitis C, just over half of them don’t know they have it.” (Some researchers put the number of undiagnosed people at closer to four million.⁵)

Because most patients who suffer from HCV do not have specific symptoms, if any, many people are diagnosed when their physicians prescribe routine blood work for a physical or to diagnose another possible illness. To confirm an HCV diagnosis, doctors may run a liver biopsy in addition to blood tests.⁶

And, even though many patients are asymptomatic for decades, the virus is not dormant. “It is slowly destroying the liver, but the symptoms are not very specific, and most people just don’t know they are ill,” says Dr. de Jong. “Patients don’t become jaundiced or have fevers or have abdominal pain from having hepatitis C. They might experience a little bit more fatigue than other people, and in very rare cases, there are complications such as skin ulcers or renal failure.”

Past Treatments

“In the past, interferon-based strategies were the only treatment for this disease,” says Dr. Chung. “Initially, our strategies revolved around either interferon given alone or interferon given with ribavirin, another antiviral, though weaker. That combination produced response rates in just over 50 percent of patients. The regimen was administered between six months and 12 months and was associated with a litany of significant side effects such as fatigue, anxiety, depression, anemia, low white blood cell and platelet counts, and provocation of autoimmune events such as lupus, rheumatoid arthritis, ulcerative colitis, psoriasis and thyroid disorders. So even though the cure rate was just over 50 percent with interferon and ribavirin, the true effectiveness was much more limited because very few patients actually went through the process of treatment. Potential contraindications, concerns about preexisting conditions, concerns about intolerability, or, for those who did start, actual intolerability, caused premature termination of the regimen. That led to very few patients being eligible or [even wanting to risk the side effects].”

Today’s “Miraculous” Hope

In 2011, a huge breakthrough was made with the advent and approval of direct-acting anti-viral drugs (DAAs). “By 2011 we had our first publications of papers, given two different regimens that showed the remarkable and long-awaited proof of concept that you didn’t need interferon to cure this virus,” says Dr. Jacobson. “We’ve always thought that if you gave the right combination of specifically targeted direct-acting antiviral agents that you could so profoundly suppress the ability of the virus to replicate that, hopefully, eventually, and perhaps with some little subtle natural help from the immune system, you could eradicate this virus. That’s exactly what we’ve learned.”

Dr. Jacobson even goes so far as to call DAAs “miraculous.” The first such drugs, Telaprevir (Incivek and Incivo) and Boceprevir (Victrelis), were considered cutting-edge in their time, but medicine has advanced so greatly and so quickly since then that the two drugs are no longer used. This, according to Dr. Jacobson, “is very fast in the grand sweep of things. It’s kind of remarkable.” Today, the focus is on more advanced DAAs such as Harvoni (ledipasvir and sofosbuvir) and the more recently approved Zepatier (elbasvir and grazoprevir).⁷ Cure rates with the latest DAAs, including protease inhibitors, polymerase inhibitors and NS5A inhibitors, are as high as 97 percent.⁸

Dr. Jacobson adds that some patient populations have been more difficult to treat, yet because of improved DAAs, they are increasingly responsive: “We leapfrogged from an era in which we still had to prove this, to an era in which an astonishingly high percentage of patients could be cured. Many had anticipated that this would occur in incremental steps. I like to say we thought it would be like the iPhone that keeps coming back in new versions year after year. That one year you could cure 20 percent, then 50 percent, then maybe 70 or 80. But instead, we’ve leapfrogged from nothing to extraordinary rates of cure, as high as 99 percent in some clinical trials.”

Investigational Treatments

In light of the unprecedented cure rates with already existing drugs, Dr. de Jong wonders whether more research into investigational drugs is needed. “So the question is really, ongoing, what are investigational drugs?” he asks. “Do we need to go to three drugs or make one pill or two pills with three active components? Where, for example, instead of treating for 12 weeks or eight weeks, can we now go to six weeks or four weeks? That’s one investigational direction the pharmaceutical companies are going. It would be ideal if a doctor could see a patient just once, give him a one-month prescription that insurance would cover, and then cure 99 percent of people with two or three drugs.”

“Now we’re focusing a lot of our attention on the relatively few patients who have treatment failure because we’ve gotten spoiled [by success],” says Dr. Jacobson. “We’re not going to leave anybody behind. And so people are developing what are called salvage or rescue regimens for the patients who do fail these regimens.”

“There are still investigational things coming down the pipeline,” adds de Jong, “but the big debate in the field is whether we still need them. Because with the drugs we already have, we are able to cure perhaps 99 percent of patients in clinical trials. The trials are always a little bit better than real life, so say that is probably going to be 97 or 95 percent. What is the pharmaceutical market going to do? And if we go to three drugs, which everyone expects us to do, with all three classes of direct-acting antivirals in one tablet, we will probably cure 90 percent of the people who didn’t respond previously. So, we’ll end up with a very small pool of patients who cannot be treated. And that is the big debate right now. Do we still need investigational drugs to cure those very few people who cannot be cured with the current medications? We don’t really know this yet.”

Final Thoughts

Regardless of the unanswered questions, one thing is certain: Cure rates are unprecedented, and being diagnosed with hepatitis C is no longer the grave event it once was. “At this juncture, knowledge is power,” concludes Dr. Chung. “Knowledge is responsibility to follow through to prove your own health. I would be very emphatic about the fact there’s no excuse for not diagnosing every last person with this infection in view of the fact we will have treatment for every one of them.”

More and more hepatitis C patients are discovering that hope. Just ask Sue Simon.