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Advances in Hepatitis C Treatment
By: R. Morgan Griffin WebMD Medical News Archive Archive Jan. 19, 2000 (Baltimore)

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. With hepatitis C treatment, about 50% of all patients can now be cured. 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

About 4 million people in the U.S. are infected with hepatitis C, according to the National Institutes of Health. 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" in about 55% 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 70-80%; people with type 1 have rates of about 40-45%. 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 55% cure rate may not sound hopeful. 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.

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.

"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 about a 70% chance that a full cycle of treatment will cure the disease. 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.

"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."

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 only about 5,200 liver transplants total in the U.S. last year. However, there are about 3 to 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.

"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 the next few years, another slightly different version of interferon may become available, as well as a new drug similar to ribavirin. Doctors hope that these medications might make hepatitis C treatment more effective with fewer side effects.

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.

One of the risks to this 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."

While targeted therapy is exciting, these drugs won't to be available soon. Experts estimate that these drugs won't even be tested in clinical trials for several years at least. No one knows when and if they'll become available to most people.

"For the next five or so years at least, treatment is going to be pegylated interferon and ribavirin," says Worman. "Or maybe some slightly better versions of those drugs."

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: "I don't think there's any vaccine that's close to being ready."

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 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 half of the time. There aren't many other examples of that."