"Q: Will we be able to wipe out hepatitis C entirely?
A: In contrast to HIV, we do have the capability of doing that - essentially curing everyone who got infected. While we have made tremendous progress against HIV, we still don't have a cure, we still don't have a vaccine. The situation for HCV is dramatically different. A cure is achievable. Someday soon, the cure using an interferon-free cocktail is going to be routine...."
Until now, I thought it was likely that this disease would kill not only my imprisoned friend Davon, sick as a dog on interferon right now, but also my big brother, who hasn't been able to get treatment - both I feared would die very painfully, at an early age.
This news gives me hope, though. We have the capability to wipe out this disease and cure those who are ill right now - the question remains: do we have the collective will? That much, I still don't know.
Nearly 6,000 AZ state prisoners have tested positive for the Hepatitis C virus, but only a fraction are deemed eligible for a miserable course of interferon treatment because it costs so much and takes such a toll on body and mind. Many drop out from the side effects, having to face debilitating and fatal liver disease instead. Most public health estimates put the jail/prison population at being over 50% HCV+. Imagine how hard it is already to see loved one do time and maybe even make amends for their crimes in prison, and come home only to find that they were sentenced to die from an infectious disease, as well.
For those who don't care about prisoners, though, think about this: since 95% of then return to the free world eventually, that means there's already an epidemic in communities with high rates of poverty, unemployment, homelessness, felonization, incarceration, uninsured persons, IV drug addiction, HIV/AIDS, and other compromised populations. It also disproportionately affects people of color, the LGBTQ communities, and Baby Boomers. That's a huge public health problem that no one in Arizona likes talking about - why are they so silent now, I wonder? Surely they've heard this by now.
It sounds like it's time for the AZ DOC and Wexford to re-write their Hep C treatment protocols, in any case, in order to assure that the standard of care they provide to prisoners with the virus (HCV) is consistent with the community's new standard. Otherwise, they can both expect to be named in a new class action lawsuit soon, I'm sure. I'd think the public at large could even sue the state for having an infected population unleashed on us - uneducated, untreated, unsupported, uninsured, and unwell.
Erin Allday / San Francisco Chronicle
Tuesday, September 11, 2012Earlier this year, an editorial in the New England Journal of Medicine declared that the world was in a "watershed moment" in the history of treatment for hepatitis C, a virus that is believed to infect roughly 180 million people globally. Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Francisco, agrees wholeheartedly - and believes that with recent advances in treatments and a cure, the world could be on the cusp of nearly wiping out the virus.
Q: What does the hepatitis C virus do to the body?
A: This is an RNA virus that infects hepatocytes, cells in the liver. That's why you ultimately get hepatitis, or inflammation in the liver, and that can progress on to cirrhosis. About 20 percent of people spontaneously clear the hepatitis C virus, and of the rest, about 20 to 25 percent will progress to cirrhosis, and eventually end-stage liver disease. Hepatitis C is the leading reason behind liver transplants in the United States.
Q: For many years, hepatitis C has been treated with interferon. What is interferon?
A: Interferon is a type of protein called cytokine. It normally triggers an antiviral response in the body. It inhibits key steps in the (hepatitis C) virus life cycle that allow it to replicate. But it's doing it at a cost. Cytokine is pretty toxic. It makes patients very sick.
Q: Last year the Food and Drug Administration approved new drugs to treat hepatitis C. How do they work?
A: It's just like with HIV - you're attacking multiple, key proteins needed for the hepatitis C virus lifecycle. Now you have these small molecules that are attacking the virus itself, as opposed to trying to induce an antiviral response, like with interferon.
These drugs are proving to be just dynamite. We're very close to being able to cure everybody of hepatitis C. The natural history of hepatitis C virus infection has been fundamentally changed.
Q: Why has hepatitis C been so hard to treat historically?
A: One thing that limited progress was the lack of an infectious molecular clone to use in the laboratory to test drugs. It was only in the last few years that an infectious molecular clone came out of Japan. Before that, none of them fully replicated (in the lab). When the molecular clones came along progress just took off at light speed.
Then the blueprint for working on HIV became very informative - protease inhibitors, polymerase inhibitors, they were all targeted very quickly, by multiple pharmaceuticals. Many of the pharmaceuticals just moved their HIV discovery teams into HCV. Progress has been made so rapidly here because the trail had been blazed by all of the HIV drugs.
Q: Will we be able to wipe out hepatitis C entirely?
A: In contrast to HIV, we do have the capability of doing that - essentially curing everyone who got infected. While we have made tremendous progress against HIV, we still don't have a cure, we still don't have a vaccine. The situation for HCV is dramatically different. A cure is achievable. Someday soon, the cure using an interferon-free cocktail is going to be routine.
Then it becomes more of an implementation issue - how you distribute these drugs, what you charge for them. There are 180 million people infected worldwide, five to six times the size of the HIV epidemic, and many are living in resource-poor settings. We're going to have to figure out how to deal with the developing world.
"It is just a remarkable moment in the history of hepatitis C," said Dr. Warner Greene, director of the virology and immunology division at the Gladstone Institute in San Francisco. "I think hepatitis C and its sequela - liver cancer, cirrhosis, liver transplants - can largely be gone in the future. We just won't have to worry about it."
In the past year, new treatments have come out that already have doubled the number of people who can be cured of hepatitis C. Now the race is on among drug developers to market the first medical cocktails that would cure almost everyone on the planet, and do it safer and faster than the best treatments currently available.
New treatments - both those already available and those expected to be approved in the next five or so years - were a large part of the reason the U.S. Centers for Disease Control and Prevention recommended this summer that all Baby Boomers get screened for hepatitis C.
That generation is thought to have the largest number of undiagnosed cases of the disease, with so many of them potentially exposed to the virus in the wild, drug-friendly hippie years of the '60s and '70s. Until recently it wasn't practical to screen millions of people for possible cases of hepatitis C because few good treatments were available.
Hepatitis C's spreadHepatitis C is a virus transmitted through the blood, similar to HIV. It's often spread through shared needles used by intravenous drug abusers. Decades ago, and even still in some developing parts of the world, people were exposed to hepatitis C through unsterilized equipment used for tattoos or surgical procedures. Also, the U.S. blood supply wasn't screened for hepatitis C until the early 1990s, so people sometimes became infected from a blood transfusion or organ transplant.
In roughly 20 percent of hepatitis C cases, the body's immune system fights off the virus without any medical intervention and probably without the individual ever being aware of having it. The remaining cases develop into chronic hepatitis C.
In some of those cases, the virus may lie dormant for decades, or even a lifetime, but in about 1 in 5 chronic cases, the virus will attack the liver, scarring it and causing cirrhosis, and potentially leading to liver cancer and liver failure. The infection causes about 10,000 deaths a year in the United States, and it's the leading reason for liver transplants. Hepatitis C is especially prevalent in people who also have HIV infections; in fact, HIV-positive patients are more likely to die of hepatitis-caused liver disease than of AIDS or HIV.
Antiviral drugsIt's only in the past seven years or so that doctors and scientists discovered the first antiviral drugs that can stop the virus, giving the body's natural immune system a chance to fight it off. The cure rate with those drugs is 75 to 80 percent, but they require that patients also take interferon, a toxic medication that can cause disabling side effects for a year.
In the next five years, researchers expect to develop even more potent antiviral medications - drugs that will cure more than 90 percent of patients, and do it in half the time and without the interferon.
"There's no question that with these new treatments, cure is going to be the rule and not the exception," said Dr. Brad Hare, medical director of the HIV/AIDS ward at San Francisco General Hospital, who studies HIV and hepatitis C co-infections. "It's more important than ever to identify people with hepatitis C, because we have something even better to offer them."
That said, Hare added, it's unlikely that the virus will ever be eradicated. There will always remain a pocket of people who don't respond to drug therapy or aren't able to take it for some reason. Those who have been cured can be reinfected.
And getting new medications to the tens of millions of people affected by hepatitis C won't be easy, especially because the drugs will almost definitely be expensive.
Strains on the systemJust screening the millions of Baby Boomers in the United States, and getting those who test positive for hepatitis C into treatment, could be an overwhelming strain on the health care system, public health experts say. Drugs in development could ease some of that burden if they're easier to take and more effective than the current treatments.
Hepatitis C was discovered in the late 1980s, although scientists had known for years that a virus existed that was causing inflammation in the liver and that wasn't the hepatitis A or B viruses.
The U.S. Food and Drug Administration approved the first treatment for hepatitis C - the chemotherapy drug interferon - in 1991, and added a second drug, ribavirin, in 1998. Those two medications were considered a breakthrough therapy for a virus that had previously been untreatable, but the treatment itself was rough and not all that effective.
The ribavirin comes in pill form, but the interferon has to be given intravenously three times a week for 48 weeks. Both drugs, especially the interferon, often come with awful side effects - major depression and, sometimes, suicidal thoughts, plus fatigue, nausea and flu-like symptoms.
And the worst of it is that the treatments lead to a cure only roughly half the time - less than half for patients with the most common strain of hepatitis C.
"A lot of us didn't have bad symptoms before we went on treatment," said Daniel Berrner, a San Francisco resident who was diagnosed with both HIV and hepatitis C in 2005, and underwent successful treatment for the latter in 2009. "People maybe feel some fatigue, but that's it. So to convince them to feel awful for a year when they're not feeling that bad to begin with is a really hard thing to do."
Because treatment was, for many people, tougher to endure than the virus itself, many doctors over the years have "triaged" patients by performing liver biopsies or blood tests to determine if hepatitis C was causing severe enough damage to treat even at the risk of failure. If patients weren't experiencing acute symptoms and their livers seemed relatively healthy, they'd often postpone treatment.
More seek treatmentWhether to get treatment for hepatitis C is still a personal decision and best made after a thoughtful conversation with a primary care doctor or a liver expert, doctors said. But increasingly patients are being encouraged to get treatment, even if their infection isn't particularly virulent.
"I still try to triage based on the risk of end-stage liver disease. But now more patients are willing to be treated," said Dr. Natalie Bzowej, a liver disease specialist at California Pacific Medical Center.
Bzowej helped lead national research into one of the first antiviral treatments that targeted hepatitis C, a protease inhibitor called telaprevir made by Vertex Pharmaceuticals, which was approved by the FDA in June 2011. A similar drug, boceprevir from Merck, also won FDA approval last year.
Remarkable successIn clinical trials, about 80 percent of patients with the most common strain of hepatitis C who took one of those drugs, plus the usual interferon and ribavirin combination, were cured. That was a remarkable improvement over the previous 40 to 50 percent cure rate.
Also encouraging: Most of the patients who were cured were able to stop taking the medications after just 24 weeks, cutting the treatment time in half.
The reason for the difference is that the new drugs single out the hepatitis C virus specifically, whereas the interferon and the ribavirin essentially just give a boost to the body's natural immune system. For many people, the immune system is not strong or fast enough on its own to fight off the virus.
Protease inhibitors are best known as a class of drugs used to treat HIV infection. They work by attacking specific enzymes, or proteases, in a virus that are a key part of the replication process. By inhibiting those enzymes, the virus is unable to reproduce and eventually dies off.
Now, scientists are looking for the next line of drugs to attack other points of the hepatitis life cycle. The pharmaceutical industry is racing toward clinical trials - companies battling to be the first to get new drugs, especially those that would make interferon obsolete, to the market.
Multidrug attackDoctors and scientists alike expect the first of the new wave of drugs to be available in four or five years. Part of the reason not everyone can be cured of hepatitis C is that, like many viruses, it mutates so quickly and becomes immune to drugs. So ideally, doctors will have at their disposal several drugs - maybe dozens - that will attack the virus on several fronts at once.
If those drugs are strong and fast enough, they could cure patients without the need for interferon. Protease inhibitors and other antiviral drugs aren't without side effects, but the symptoms are much less severe than those from interferon, and the newest classes of drugs may work in as little as 12 weeks, or about half the time it takes telaprevir, the protease inhibitor, to do the job.
"I feel like we are glimpsing the beginning of the end for hepatitis C," said Dr. Cami Graham, vice president of global medical affairs at Vertex. "We really are beginning to see what that path to eradication is going to look like."
Long incubation periodBoth drug developers and doctors alike said they are advising patients not to raise their hopes too high. Almost all of the clinical trials are in their earliest stages, and for the Baby Boomers especially, patients with decades-old infections may not have even a few years to wait for new treatments.
"What we have now is better than anything we've had in a long time," said Dr. Joanna Ready, chief of gastroenterology at Kaiser Santa Clara. "What will be even better is interferon-free therapies, and the early studies have been very, very, very promising. But the disease has such a long incubation period and damages the liver over decades, so we really need to be following people over time.
Still, Ready said, she's hopeful.
"If we don't wipe out hepatitis C entirely, we can probably make it go away like polio, where you haven't gotten rid of it but you've really beaten it down," she said. "The science behind these treatments is improving every day. And the more we know, the better we are at treating it."
Erin Allday is a San Francisco Chronicle staff writer. E-mail: email@example.com