Turning the Corner in Hepatitis C Treatment

Last Editorial Review: 6/30/2005

Newer medications are making a difference, and better ones may be on the way.

WebMD Feature

Reviewed By Charlotte Grayson

Getting diagnosed with hepatitis C can be frightening, and it's natural to worry. You may have heard that treatment is difficult. Or you may wonder if you'll need a liver transplant someday. But while hepatitis C is undeniably a serious disease, it's not as bad as many people imagine.

"For people who have just been diagnosed, it's normal for hepatitis C to be a source of worry," says Paul Berk, MD, professor of medicine at Mt. Sinai School of Medicine and Chair of the American Liver Foundation. "But it shouldn't be a source of panic."

The facts are reassuring. Even without treatment, most people with the hepatitis C virus (HCV) live decades without having any symptoms. According to the Centers for Disease Control and Prevention (CDC), between 40-80% of all patients can now be essentially cured with current treatment regimens. Moreover, new drugs are in development that may radically improve the prognosis.

This is impressive progress for a disease that was only identified in 1989.

"If you've been newly diagnosed, you really should be optimistic," Berk tells WebMD. "This is a disease that's going to be manageable."

Understanding Hepatitis C

Almost 4 million people in the U.S. are infected with hepatitis C, according to the CDC. Most don't know they have it. Hepatitis C causes few symptoms. Indeed, many of the people who are infected have had the virus for years. They may have contracted it from a blood transfusion or organ transplant before 1992, when supplies began to be screened for the disease.

There are at least six different subtypes of the hepatitis C virus. While no one type is more dangerous than another, they do respond differently to treatment. Hepatitis C Type 1 is the most common type in the US. Unfortunately, the medications we have don't work as well with Type 1 as with other subtypes of the virus.

Current Hepatitis C Treatment

For years, the standard hepatitis C treatment was a combination of injected interferon and the oral antiviral drug ribavirin. Recently, a new form of interferon -- peginterferon, or pegylated interferon -- has become the standard of care. It's a significant step toward better treatment.

"Combination treatment with pegylated interferon and ribavirin is giving us appreciably better results than what we used to get," says Berk.

Interferon is a manufactured version of certain natural proteins that fight viruses. Peginterferon, or pegylated interferon, is modified so that it stays in the body longer than standard interferon. Because the drug stays at more constant levels in the body, patients need only one injection a week instead of three.

Hepatitis C treatment with peginterferon and ribavirin achieves a "sustained response" up to 54% of people, which means that the virus has been eliminated from their blood after stopping treatment. People with hepatitis C types 2 and 3 have sustained response rates of about 80%; people with type 1 have rates of up to 50%. As far as we know, a sustained response means that the illness is cured, says Berk.

Berk also believes that hepatitis C treatment is better now because doctors now use various hormones that can counteract drops in blood cell counts, a common side effect of treatment. In the past, these side effects might make a doctor reduce the dose, or stop treatment altogether. Now it's possible to correct the side effects and carry on.

In cases where a person can't tolerate the effects of ribavirin, it's possible to use pegylated interferon on its own. However, the treatment is less effective. Ribavirin by itself doesn't work.

The Trouble With Treatment

While hepatitis C treatment has come a long way, there are still drawbacks. For a person who's newly diagnosed, a 54% cure rate may not sound great. After all, it means that about one out of two people won't respond to treatment.

Also, hepatitis C treatment is less effective in some populations. For reasons that no one understands yet, African-Americans are less likely to benefit from treatment. And the treatments may not be safe for people with other medical conditions -- such as kidney failure, heart disease, or pregnancy. Interferon can also be expensive; according to the American Academy of Family Physicians, it can cost $6,000 per year.

Even when hepatitis C treatment works, it can be difficult. Therapy lasts from 24 to 48 weeks. It requires weekly injections and regular check-ups. While pegylated interferon causes less severe side effects than older drugs, it can cause flu-like symptoms, fatigue, depression, muscle aches, and hair loss. More severe side effects are rare. Ribavirin can also cause potentially serious anemia.

"A lot of people come in expecting the treatment to be awful," says David Thomas, MD, professor of medicine at Johns Hopkins School of Medicine. "But it's often not so bad."

Also, while the length of treatment -- up to a year -- might seem daunting, Thomas encourages his patients to look at it in smaller steps.

"Within a couple of months of starting treatment, we can usually tell if it's working," Thomas says. He explains that if tests show that treatment isn't working after a few months, it's very unlikely that a full year's worth will do any good. As a result, your doctor may suggest stopping treatment.

But if treatment is working after a few months, there's almost a 70% chance that a full cycle of treatment will cure the disease, says Thomas. So a person has a good idea if treatment will work before committing to a whole year of it.

Who Needs Hepatitis C Treatment?

Before a person gets caught up in the pros and cons of treatment, it's important to consider a more basic question: do you need treatment at all? In many cases, you don't.

"A lot of people and even some doctors act like hepatitis C is cancer," says Howard J. Worman, MD, associate professor of medicine at Columbia University's College of Physicians and Surgeons. "They behave as if you'll get sick and die if you don't treat it right away. But that isn't what hepatitis C is like."

Since hepatitis C may not cause problems for decades, if at all, merely having the virus is no reason to begin treatment. Instead, doctors usually consider hepatitis C treatment in people who have high viral levels and biopsies that show fibrosis, or scarring of the liver.

"Deciding whether to get treatment is almost never an emergency," Worman tells WebMD. "It's usually not even urgent. People should take their time in deciding what to do."

In cases where a person has acute hepatitis C -- meaning that he or she has recently been infected - Worman does advise quick treatment because it's likely to work in the early stages. However, he and other experts don't see many cases of acute hepatitis. Most of the people newly diagnosed with hepatitis C have had the virus for a long time.

One frustrating aspect of the disease is that it's hard to predict how it will develop in any one person. While many people will go decades without problems, others will have faster progression of the disease. No one knows why. Currently, the only good way to find out how a person is doing is with periodic liver biopsies.

If Treatment Doesn't Work

Don't assume that you will suffer serious complications if treatment fails. It's true that there is no other combination of medications that works as a second line of defense right now. But behavioral changes, such as reducing or cutting out alcohol, can make a difference. The disease itself progresses so slowly that researchers may develop new hepatitis C treatments before you run into serious problems, if you ever do at all.

Doctors and researchers are also looking into the possibility that continuing treatment with peginterferon and ribavirin may have benefits even in people who didn't have sustained response. Continued therapy may be able to suppress the virus, even if it can't get rid of it. However, because treatment does have risks, it's important to be cautious in prescribing long-term therapy.

"A lot of people are doing research on the benefits [of continued therapy]," Thomas tells WebMD. "We're trying to figure out whether it helps."

Researchers are currently looking at other drugs that might help. One possible approach is to add a third drug -- amantadine -- to pegylated interferon and ribavirin. Preliminary results look like the triple combination might help, but more research is needed.

Also, don't worry that you're on an irrevocable path to a liver transplant. You may have heard the statistic that hepatitis C is the leading cause of liver transplants in the US. While it's true, that statistic shows just how common hepatitis C is in the population. According to the Organ Procurement and Transplantation Network there were fewer than 6,200 liver transplants total in the U.S. in 2004. However, there are almost 4 million people with hepatitis C in this country. So you don't need to be a statistical wiz to see that the vast majority of people with hepatitis C never need a liver transplant.

Worman encourages his patients to look at a possible transplant from a positive perspective.

"Instead of being afraid of that small chance that they'll need a transplant," Worman says, "I tell my patients to look at it as an insurance policy. Most people never get that sick. But if you're one of the few who do reach that stage, you should be assured by the fact that even then, we can still do something."

Alternative Therapies for Hepatitis C

Turning to alternative therapy may be tempting for people with a disease like hepatitis C. After all, treatment is difficult and may not work in half the people. You may feel like there's no harm in giving an alternative treatment a shot first.

Understand that no matter what you might find in books or on the Internet, researchers have not found a diet, supplement, or herbal remedy proven to treat hepatitis C.

"I think there should be studies of these alternative medicines," says Thomas. "But until we have good evidence, they should be considered experimental."

Some herbs that look more promising than others. Milk thistle has been used for centuries for various liver complaints, and studies have shown mixed results. Currently, the National Center for Complementary and Alternative Medicine at the National Institutes of Health is sponsoring a clinical trial of milk thistle in people with hepatitis C. [NOTE for JAYNE: I checked and there are no results yet, it seems.]

"My patients are very interested in alternative treatments like milk thistle, and I am absolutely convinced by the amount of evidence that milk thistle is safe," says Berk. "However, I'm not convinced that milk thistle is really effective."

Thomas agrees. "I generally say milk thistle is okay to my patients," says Thomas. "But only after we've gone over any other medications they're taking that might cause interactions with milk thistle."

Those interactions can be dangerous. Berk and Thomas both stress that other herbal remedies and supplements may be much less safe.

"People need to think of herbal remedies as drugs, which is what they really are," says Thomas. "There have been some people who died from liver failure as a result of some of these alternative medicines."

Anyone with hepatitis C absolutely must talk to his or her doctor before taking any herbal remedies or supplements.

New Drugs for Hepatitis C

While combination therapy with pegylated interferon and ribavirin has made a difference, new treatments are still needed for hepatitis C. In coming years, slightly different versions of interferon may become available, as well as a new drug similar to ribavirin. Researchers are also looking into the possibility of inhaled -- rather than injected -- interferon. Doctors hope that these new medications might make hepatitis C treatment more effective with fewer side effects.

However, doctors are much more excited about the next generation of medicines.

"In the next ten years, we'll hopefully be moving away from interferon and ribavirin to more specific drugs that attack the virus itself," says Worman.

Interferon and ribavirin both have general antiviral properties, but researchers are now working on various drugs that will specifically target the hepatitis C virus, interfering with the way it replicates itself. These drugs will be similar to the drugs used to fight HIV, such as protease inhibitors.

Early studies of these new drugs have been mixed. Researchers had to stop testing one promising antiviral drug when it turned out to harm the heart.

However, experts had much more success with another drug manufactured by Vertex Pharmaceuticals. Of eight people treated with the ideal dose of the drug for 14 days, half had a 25,000-fold drop in their hepatitis C levels. The disease was undetectable in two patients. Considering that standard treatment takes months to achieve similar results, the effects were striking.

However, much more research needs to be done. Even if further studies prove that the new drug works and is safe, it will be many years before it becomes available. One of the risks to this antiviral approach is that, potentially, the virus could become resistant to these drugs over time. This is what happened with HIV.

"We could run into drug resistance," admits Worman. "But hopefully, we'll come up with multiple drugs that attack different targets. We could use them in combination, or use one to replace another that fails."

Many other companies besides Vertex are working on similar drugs. But while targeted therapy is exciting, it's not going to be available soon. For the next several years at least, treatment will still be pegylated interferon and ribavirin, says Worman. "Or maybe some slightly better versions of those drugs," he adds.

Other Advances

Researchers are working on other ways to improve the lives of people with hepatitis C. While the liver biopsy remains the best test to evaluate the disease, it has drawbacks: namely, no one likes to be poked with a big needle. Researchers hope to develop blood tests that could test for cirrhosis and spare people the discomfort and mild risks of biopsies.

"I'm really hopeful about blood tests that might replace biopsies," says Thomas. "That research has some of the greatest promise in near to mid-future."

Researchers are also working on therapeutic vaccines. These wouldn't prevent the disease, but could be given to a person who's already infected to help fight the virus.

"There are some drug companies that are putting a lot of resources into hepatitis C vaccines and there are some promising leads," says Berk. But, he cautions that we're still years away from using any of them.

Hope for the Future

While it may be discouraging to learn that the next generation of hepatitis C treatments is still a few years away, it's important to keep things in perspective. Hepatitis C progresses slowly. Most people infected today may be able to take advantage of these drugs when they're available.

For the time being, experts encourage people with hepatitis C to be optimistic.

"If you're someone who doesn't need treatment right now, try to relax about it," says Thomas. If you do need treatment, try to be comforted by the fact that we can cure this disease [over] 50% of the time."

Berk agrees. "As much as we want better therapies, the success we've had so far is pretty amazing," says Berk. "We can now take a serious, chronic viral illness and cure it [over] half of the time. There aren't many other examples of that."

Medically updated June 2005.

Originally published March 2004.

SOURCES: Paul Berk, MD, Professor of Medicine and Emeritus Chief of the Division of Liver Disease, Mount Sinai School of Medicine, New York City; Chairman of the Board of the American Liver Foundation. Alan Franciscus, Executive Director, Hepatitis C Support Project and Editor-in-Chief of HCV Advocate, San Francisco. Thelma King Thiel, Chair and CEO of the Hepatitis Foundation International. David Thomas, MD Professor of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. Howard J. Worman, MD, Associate Professor of Medicine and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York City. The American Gastroenterological Association web site. The Centers for Disease Control web site. The Hepatitis Foundation International web site. The HCV Advocate web site. Medscape Conference Coverage, based on selected sessions at the 54th Annual Meeting of the American Association of the Study of Liver Diseases. November, 2003. The National Center for Complementary and Alternative Medicine (National Institutes of Health) web site. The National Digestive Diseases Information Clearinghouse (National Institutes of Health) web site. The National Institute of Allergic and Infectious Diseases (National Institutes of Health) web site. The Organ Procurement and Transplantation Network web site. WebMD Medical Reference in Collaboration with Healthwise: "Health Guide A-Z: Hepatitis C." WebMD Medical Reference: "Newly Diagnosed: Hepatitis C." WebMD Scientific American Medicine. Gastroenterology: VI. Acute Hepatitis. 1-10. WebMD Scientific American Medicine. Gastroenterology: VII. Chronic Hepatitis. 1-9. WebMD Medical News. "Hepatitis C Drug Rocks Virus in Early Test." American Academy of Family Physician's FamilyDoctor web site. Wedemeyer, H. Management of Hepatitis C -- Addressing the Issues Beyond the Guidelines. May 12, 2005, Medscape web site. Heathcote, J. Journal of Viral Hepatitis, 2005; vol 12: pp 223-235. Papatheodoridis, G. Journal of Viral Hepatitis, 2005; vol 11: pp 287-296. Pawlotsky, JM. Seminars in Liver Disease, 2005; vol 25: pp 72-83.

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