From a No-Name Virus to a Cure: Treatment Options Blossom for Hepatitis C
Twenty-five years ago, it didn't even have a name.
There were hepatitis A and B, plus a newcomer, known by exclusion as non-A non-B. Only after this liver-destroying virus was formally discovered in 1989 did it receive its own letter: C. Later that year, early clinical trials of interferon, an early biotech wonder, were published. Within two years, the drug won FDA approval despite significant side effects. Soon, interferon was helping about 10 percent of those treated for hepatitis C virus (HCV).
Since then, prospects for those with HCV vastly have improved. New drugs recently have been developed, improving response rates and reducing side effects. More than a dozen are now in the testing and approval pipeline.
"Now we can cure the majority of patients," said Donald Jensen, MD, professor of medicine and director of the Center for Liver Diseases at the University of Chicago Medicine. "In less than two years, we'll have results from large-scale trials of targeted antivirals that will mean more cures with far fewer side effects. I'm hoping it will put me out of business."
But Jensen can't retire just yet. An estimated 4 million Americans have hepatitis C, which can cause cirrhosis, liver failure and death. HCV is the fastest-growing cause of cancer mortality at a time when deaths from most types of cancer are declining. In 2007, HCV moved ahead of HIV, the virus that causes AIDS, as a cause of death in the United States.
These statistics help to remind the nearly 150 patients of Jensen and his colleagues, who were invited this month for a reunion on campus, how lucky they are to have access to treatment options and to have been cured of hepatitis C.
"People, even those at significant risk, don't get tested because there's a widespread misconception, even among many physicians, that this virus is not curable," said Jensen, a pioneer in the treatment of hepatitis. Some people do have a recurrence after treatment, and many delay treatment because they are concerned about the side effects.
Last fall, the Centers for Disease Control and Prevention advised an entire generation--the Baby Boomers, almost 80 million people born between 1945 and 1965--to get tested for hepatitis C. People born during that period are five times more likely than other adults to be infected. One-time screening of that group would find an estimated 800,000 undiagnosed cases, according to the CDC, and could prevent more than 120,000 deaths.
"That's one reason we organized the reunion," Jensen explained. "This is a chance for those who have been cured to pay it forward, to send a message to those who have avoided testing or treatment that there is light at the end of the tunnel."
Treatment used to involve three interferon injections a week for up to 48 weeks; a timed-release version later reduced that to once a week. In 1998, the FDA added a second drug, the antiviral ribavirin, taken twice a day by mouth, to the standard regimen.
Patients on interferon typically complain of profound fatigue, depression, nausea and diarrhea. Adding ribavirin has increased the cure rate from 10 to 20 percent, even up to 50 percent, depending on the viral strain and patient compliance. But it also amplifies the flu-like symptoms and can aggravate anemia.
"I slept for 14 hours a day for three days after each interferon shot," recalled Loretta Galvin, who flew back and forth from Tampa, Fla., for nine months to be treated by Jensen. "I just shut down every Sunday morning."
But it was worth it; the medications worked. Since her last shot in October 2011, Galvin has had no detectable virus. A patient with no hint of recurrence after six months is widely considered to be cured.
Since 2007, a series of new drugs has begun to advance the cause. Borrowing from progress in battling HIV, scientists developed several direct-acting antiviral (DAA) agents that precisely target viral enzymes, preventing the virus from making copies of itself.
Adding one type of DAA, which targets an HCV protease enzyme, to the interferon-ribavirin cocktail significantly improved cure rates, into the 70 to 80 percent range for certain patient groups. In a 2011 editorial in the New England Journal of Medicine, Jensen described these drugs as a "new era of therapy for hepatitis C virus" and as a "major advance in our ability to treat chronic HCV infection."
These drugs also injected new side effects. Rigoberto Rodriguez, a landscaper from St. John, Ind., participated in a clinical trial that included one of these drugs, along with interferon and ribavirin, after his disease recurred following standard treatment. The new drug, teleprevir, caused dysgeusia, an altered sense of taste. Everything "smelled like burning metal and tasted like cardboard," he recalled.
Rodriguez was encouraged to eat lots of fatty foods, because they increased uptake of the drug, but "the fats made you go," he said, "and when you went, it burned. It was like lighting a match back there."
He lost about 40 pounds during the course of treatment, but he toughed it out, never missing a day of work because of his medications. He regained "about the right amount" of weight after the trial, he said, and has been virus-free since June 2012.
Judy Palmer, a nurse from Yorkville, Ill., had a similar story. Interferon and ribavirin reduced her virus to undetectable levels, but the disease rebounded after treatment stopped. She enrolled in a clinical trial run by Jensen in 2010 that included a protease inhibitor. Palmer completed her treatment more than one year ago. She has no detectable virus and her liver function has improved dramatically. "I didn't think I would ever see this," she said.
Such rapid and extensive progress has created novel ethical issues. Shortly before the first DAAs won FDA approval in 2011, Jensen and colleague Andrew Aronsohn, MD, assistant professor of medicine at the University of Chicago, were concerned there would not be enough medication or clinic staff to handle the predicted demand. They published an editorial in the journal Hepatology arguing that the sickest patients should be treated first. Their predictions were on target. They heard from about 200 patients in the first few weeks after the drugs were approved.
One year later, however, with exciting new trials that rely entirely on combinations of DAAs--and no interferon--Jensen and Aronsohn noticed that many potentially curable patients were choosing to delay treatment. Potential patients, some with progressive liver damage, were speculating that better medications would make it to market before their disease advanced. A follow-up Jensen-Aronsohn editorial stressed the importance of what they called "informed deferral." They urged hepatologists to initiate an active process to educate patients about specific risks and to weigh that against the benefits from the newer drugs, rather than letting them make such decisions in a vacuum.
One patient who entered treatment at the right time was R.H., from Mich., who acquired hepatitis C from multiple blood transfusions following a serious motor vehicle accident in 1986, six years before a blood test for HCV became available. On his doctor's advice, R.H.'s hepatitis went untreated for almost 25 years.
After recovering from the accident, R.H. worked hard at staying fit. While in his 20s and 30s, he ran 10 marathons, usually in less than four hours. He also completed five Ironman triathlons--which consist of a 2.4-mile swim, a 112-mile bike ride, followed with a 26.2-mile run.
Then in 2010, his employer sent him to the University of Chicago for an executive physical--company policy--where they found that his long-dormant virus was now active. He was referred to Jensen, who quickly enrolled him in a study that combined interferon, ribavirin and a promising new DAA, known as sofosbuvir.
"In four days," he said, "my viral count went from 4 million International Units to 'undetectable.' "
The treatment did not come without a cost. Before the study began, his nurses, impressed by his athleticism, called him "Superman." The drugs, it turned out, were his kryptonite.
They "brought me to my knees," he said. "Monique Williams, my main nurse, still called me Superman, but I was no Superman. I had every possible downside."
He also developed a very personal side effect. He became emotional, even tearing up when he watched movies like "Bambi" with his daughters, ages 3 and 1 at the time. "This became sort of a joke at home," he said, "but it could be awkward on the job. I had to slip out of some meetings."
But the drugs worked, and one year after completing the study, R.H. is considered cured. In May, he and his wife will have a third daughter. "Maybe a fourth," he added. "Who knows?"
Those words of optimism were like music to his physician's ears. "This is how we like these stories to end," Jensen said.
In the meantime, one of Jensen's missions is to continue to educate the public because progress in treating hepatitis C is "an insufficiently heralded victory," he said.
"A few years ago when standard treatment could eliminate the virus from maybe half of all patients, the American Liver Foundation put out a pamphlet that said there was no cure," he said. "Last year, at a time when 75 percent of patients could be cured, a screening task force implied there was still no curative treatment.
"In 2014, when we get final data from trials already under way that are getting better than 90 percent cure rates without interferon, I want people with this common disease to understand we can help them. We can get rid of this virus. There is a cure."