DRUGS & CONDITIONS

WHAT IS HEPATITIS C?

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Many people have heard of the type of hepatitis that is spread by water or food contaminated with the hepatitis A virus. A diagnosis of hepatitis C, however, is often more puzzling. Your doctor has probably given you some basic facts about hepatitis C, and these articles are designed to help you learn more.

"Hepatitis" -- a term that means inflammation of the liver -- can have many causes. At least six distinct viruses are known to cause hepatitis. The first to be discovered were hepatitis A and hepatitis B. In 1989, researchers isolated another virus that causes liver disease. Originally it was named for what it was not: non-A, non-B hepatitis. Now it is known as hepatitis C virus (HCV).

Although all these viruses target the liver, they differ in many other ways. Hepatitis A is generally transmitted in food or water contaminated with the stool of someone with hepatitis A. This virus causes an acute illness that is usually relatively mild and always goes away on its own. Hepatitis B is spread through contaminated blood or via sexual contact with an infected person. It's a more dangerous virus that, in about 10 to 20 percent of cases, can cause persistent infections (called chronic infections), damage the liver over time, and even lead to liver cancer.

Hepatitis C, or HCV, accounts for only about 15 percent of cases of viral hepatitis. Only 15 to 25 percent of those infected with HCV are able to rid their bodies of the infection completely without treatment. The course of the disease varies greatly from patient to patient; as an overview from the National Institutes of Health points out, "At one end of the spectrum are patients who have no signs or symptoms of liver disease... The degree of injury is usually mild, and the overall prognosis may be good."

In most people, however, it causes a persistent, at times serious, illness. Seventy percent of all cases of chronic hepatitis are caused by HCV. In the United States, it is a leading cause of serious liver disease, including cirrhosis (scarring of the liver), liver failure, and liver cancer. In fact, roughly half of all cases of liver cancer in the US, are due to hepatitis C. Liver failure as a result of HCV infection is one of the leading reasons for liver transplants in America.

The global threat

Because symptoms are absent or hard to detect, hepatitis C virus usually often goes undetected for years, even decades, before causing serious illness. For that reason, it has been called the "silent epidemic." Yet hepatitis C poses a serious health threat around the world. Worldwide, more than 200 million people are believed to be infected with the virus. An estimated 4.1 million Americans -- or 1.3 percent of the population -- carry it. Of those, approximately 3.2 million have chronic hepatitis C.

In fact, more people are infected with HCV than with the AIDS virus. Hepatitis C is responsible for 8.000 to 10,000 deaths in the United States each year. Many people were exposed to the virus through transfusions of contaminated blood, before researchers identified hepatitis C and created tests to screen for it in the blood supply. Sharing of needles for intravenous drug use also spreads the virus.

A small but devious germ

What makes hepatitis C so dangerous? Part of the answer lies in the nature of viruses. These germs are among the smallest known disease agents. They consist of strands of genetic material containing instructions for creating new viruses, usually wrapped in a protective coating.

On their own, viruses cannot reproduce or propel themselves. But once they invade healthy cells, they take over and turn them into factories that churn out new viruses. Thousands of nearly identical copies of HCV can emerge from an infected cell. These can then infect other nearby cells. In the process of turning cells into virus-producing factories, many viruses ultimately end up killing the cells they invade, although this is generally not the case with HCV.

Even among viruses, hepatitis C is extremely small -- only 50 nanometers. A nanometer is one-billionth of a meter. Hundreds of thousands of hepatitis C viruses could gather on the period at the end of this sentence. In fact, hepatitis C viruses are even smaller than the wavelength of visible light. Hence, they have no color. What makes this vanishingly small virus so dangerous is that it can escape the immune system, whose job is to identify and kill invading viruses and other organisms.

Unlocking HCV's attack strategies

How HCV survives is still partly a mystery. Yet researchers have discovered a few of its strategies. The most important is its ability to change its shape. Each time the immune system produces antibodies against hepatitis C -- molecules designed to latch onto it and destroy it -- the virus changes its outer shape. Then the antibodies no longer lock onto the virus.

HCV uses other strategies to disarm the immune system. In 2003, researchers at the University of Texas discovered that hepatitis C virus produces an enzyme that blocks a molecule the immune system needs to attack foreign invaders. With this "master switch" shut down, the virus can gain a foothold.

Despite these strategies, some people's immune systems are able to fight off hepatitis C and eliminate it. In a majority of people, however, HCV eludes the immune system and causes a chronic, or persistent, infection. The virus goes on infecting new liver cells and using them to multiply and spread. At least three out of four people infected with hepatitis C virus develop chronic infection that causes liver disease. Why some people fight off HCV and others develop chronic infections isn't well understood.

What is now known is that many people with hepatitis C respond well to treatment. One 2007 study of nearly 1,000 hepatitis C patients found that some showed no sign of the disease for as long as seven years. "On average, 50 percent of the people we treat are cured by the treatment," says Emmet Keeffe, MD, chief of hepatology at Stanford University Medical Center.

The different faces of HCV

One reason hepatitis C infection varies may be the fact that there are many varieties of the virus. Researchers have identified at least six genetically distinct types of HCV, called genotypes (a genotype consists of all the genes in a given organism). There are also more than 50 subtypes. Genotype 1 is the most common virus found in the United States.

When someone is found to be infected with HCV, doctors usually test the genotype of the virus so they can make treatment recommendations. Patients with genotypes 2 and 3 are 50 percent more likely to respond to commonly used therapies than patients with genotype 1. Knowing the genotype helps doctors determine the ideal length of treatment. A 24-week course of combination treatment is usually adequate for patients with genotypes 2 and 3, for example. Patients with genotype 1 typically require a 48-week course of treatment.

It is possible to be infected with more than one genotype. People infected with hepatitis C can also be infected with hepatitis B, another virus that can cause chronic liver disease, as well as with HIV, the virus that causes AIDS.

Rapid progress on many fronts

Being diagnosed with hepatitis C is a frightening experience. But it tends to be a slow-moving disease, and many people infected with HCV live for years without ill effects. In addition, important and rapid progress is being made in understanding the virus and its effects. That knowledge is leading to new and better treatments.

Because the disease develops so slowly, many people with hepatitis C can expect to die of old age or other conditions instead. As hepatologist Keefe points out: "More people die with hepatitis C than because of it."

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, G.L., et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Gresens, C.J. et al. The disappearance of transfusion-transmitted hepatitis C virus infections in the United States, Clinical Liver Disease, Nov 2001, pp 1105-13

Seeff et al. The National Institutes of Health Consensus Development Conference management of hepatitis C 2002, Clinical Liver Disease, Feb 2003, pp 261-87

Farci, P. et al. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies, Science, 2000, pp 339-44

Foy, E. et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease, Science 2003 300: 1145-1148

Thomas, D.L. et al. The natural history of hepatitis C virus infection: host, viral and environmental factors, Journal of the American Medical Association, July 26, 2000, pp 450-6

American Medical Association. Cure rates becoming the norm for patients with hepatitis C. June 2007. http://www.ama-assn.org/amednews/2007/06/18/hlsc0618.htm

National Digestive Diseases Information Clearinghouse. Chronic Hepatitis C: Current Disease Management. November 2006. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/

Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing tends in hepatitis C-related mortality in the United States, 1995-2004. Hepatology. April 2008; 47(4): 1128-35.

Johns Hopkins Hospital. Hepatitis C: The Silent Epidemic. September 30, 2002.


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated August 12, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

WHO GETS HEPATITIS C?

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Who gets hepatitis C?

Anyone can get hepatitis C virus. But unlike a cold or flu virus, HCV isn't easy to catch. The virus is transmitted only by direct contact with human blood that contains the virus. There are several ways infection can occur. Those at risk of being infected with hepatitis C virus include:

People who have one or more of the above risk factors should contact their health care provider and ask to be tested for hepatitis C. If you have persistently abnormal liver enzyme, or ALT, levels, you should get the test as well.

What about tattooing?

Tattooing is not considered a risk factor for HCV infection, according to the Centers for Disease Control and Prevention (CDC). Some studies have shown a link between tattooing and the infection in very select groups of people, but the agency says there's not enough evidence to say the same is true for the general population.

The agency does, however, advise people thinking about getting tattoos or body piercing to consider the health risks. It's possible to get infected with HCV, the CDC says, if the tools used have someone else's blood on them, or if the piercer or tattoo artist fails to use proper hygiene, such as washing hands, sterilizing tools, and using disposable gloves.

Is it possible to contract HCV from a shared razor or toothbrush?

There are no documented cases of transmission, but the CDC warns that people should not share toothbrushes, razors, or other personal care items: They might have small amounts of infected blood on them.

If you or someone in your household is infected with HCV, it's very important to take steps to prevent transmission. Do not share personal items such as toothbrushes, razors, or manicuring scissors -- supplies that could be contaminated with tiny flecks of blood. Avoid contact with open cuts or sores.

The CDC stresses that the hepatitis C virus is NOT spread by casual contact or by breast feeding, hugging or kissing, sneezing, coughing, or sharing utensils, drinking glasses, food, or water.

Is sex safe?

There is also a very small risk of transmission through sex with a person infected with HCV. Experts note that this occurs only very rarely. Less than 1 percent of partners in monogamous relationships with an HCV-infected person become infected each year. That risk runs to up to 10 percent if a relationship lasts over several decades. Most federal health agencies advise monogamous couples in which one partner has hepatitis C not to change their sexual behavior because of the virus.

People who have multiple sex partners should always use a condom. Scientists don't know for certain that condoms can block HCV transmission. But they do block sexually transmitted diseases such as HIV/AIDS. If you have HCV and have sex with multiple partners, it is essential to use a condom.

In about 10 to 30 percent of cases, doctors are unable to reliably identify the way hepatitis C was transmitted. This doesn't mean the virus is spreading in some way scientists haven't identified. It means instead that doctors are sometimes unable to identify which of the known modes of transmission may have spread the virus to a certain patient.

Preventing the spread

The more we know about HCV, the better equipped we are to prevent its spread. Fortunately, the number of new cases of hepatitis C infection has been declining. However, hepatitis C-related deaths are on the rise and are expected to increase even more as the number of people with longstanding infections continues to rise. By identifying the virus and developing tests to detect it, researchers have almost completely eliminated transmission through blood transfusions and organ transplants, for instance. Substance abuse programs, including information about the dangers of sharing needles and programs that provide free disposable needles, may account for the recent decline of HCV among intravenous drug users. Researchers hope to find ways to reduce the risk to newborns born to HCV-positive mothers, as well.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, G.L., et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Gresens, C.J. et al. The disappearance of transfusion-transmitted hepatitis C virus infections in the United States, Clinical Liver Disease, Nov 2001

Seeff et al. The National Institutes of Health Consensus Development Conference management of hepatitis C 2002, Clinical Liver Disease, Feb 2003, pp 261-87

Thomas, D.L. et al. The natural history of hepatitis C virus infection: host, viral and environmental factors, Journal of the American Medical Association, July 26, 2000, pp 450-6

Hepatitis C Prevention. National Center for Infectious Diseases/Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/diseases/hepatitis/c/hepcprev.htm

CDC's Position on Tattooing and HCV Infection. Viral Hepatitis C. National Center for Infectious Diseases/Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/diseases/hepatitis/c/tattoo/htm

Centers for Disease Control. Viral Hepatitis C. December 2006. http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm

American Cancer Society. Possible Risks of Blood Product Transfusions. November 2006. http://www.cancer.org/docroot/ETO/content/ETO_1_4x_Possible_Risks_of_Blo...

National Institute of Diabetes and Digestive and Kidney Diseases. Chronic Hepatitis C: Current Disease Management. November 2006. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc

Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing tends in hepatitis C-related mortality in the United States, 1995-2004. Hepatology. April 2008; 47(4): 1128-35.


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated August 12, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HOW DOES IT SPREAD

Unlike cold or flu viruses, the hepatitis C virus (HCV) does not spread easily. It is transmitted by direct contact with blood that carries the virus. Before screening donated blood for hepatitis C became mandatory in 1991, most transmission occurred through blood transfusions.

Now that the blood supply is tested for the hepatitis C virus, this kind of transmission is extremely rare: It occurs less than once in every two million units of blood transfused. In the past, the virus was also spread through transplanted organs from people infected with HCV. Today, that risk has all but been eliminated.

One of the main ways the virus continues to be transmitted is through the injection of illegal drugs -- this accounts for 60 percent of all new cases of hepatitis C, according to the Centers for Disease Control and Prevention (CDC). Drug users who share needles are at very high risk of being exposed. Sharing a needle just once is enough to be exposed to the virus, even if that exposure took place decades ago.

The hepatitis C virus can spread in other ways as well. Mothers infected with the virus can transmit it to their babies during childbirth. About four out of every 100 infants born to infected mothers contracts the illness. Mothers who have hepatitis C often worry about spreading the virus to infants through breast milk. However, experts say there is no evidence that the virus is transmitted through breastfeeding. Still, to be safe, mothers who've tested positive for the hepatitis C virus whose nipples are cracked or bleeding should not breastfeed until their nipples heal.

Laboratory workers and medical personnel also run the risk of being exposed to the virus through accidental sticks from needles or other "sharps." Fortunately, this is not a very effective way to transmit HCV -- fewer than two people in 100 exposed to a stick from a contaminated source will become infected, according to the CDC. However, plenty of people with the hepatitis C virus do not report any of these risk factors, and the mode of transmission remains a mystery.

And unlike the virus that causes AIDS, the hepatitis C virus does not spread easily through sexual contact. Research shows there is some risk of transmission through sexual intercourse, but it is minimal. Couples in a monogamous relationship do not need to take any additional precautions when one partner is diagnosed with the hepatitis C virus. People who have sex with multiple partners should always use a condom to prevent sexually transmitted diseases.

Knowing how hepatitis C virus doesn't spread is as important as knowing how it does spread. The virus is not transmitted by sneezing, coughing, or sharing eating utensils or drinking glasses. It's also not spread through food, water, or casual physical contact like hugging or kissing. The only risk to people in a household comes from sharing personal items that may transmit blood from one person to another. These include razors, toothbrushes, and manicuring items such as nail clippers.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, GL. et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.

Morbidity and Mortality Weekly, Centers for Disease Control and Prevention, June 29, 2001.

Viral Hepatitis C, National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/diseases/hepatitis/c/

Centers for Disease Control. Frequently Asked Questions About Hepatitis C. http://www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm#2c


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated December 17, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

WHAT ARE THE SYMPTOMS OF HEPATITIS C?

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The symptoms of hepatitis C virus infection differ widely from one person to another. After being exposed to the virus, some people experience a short bout of symptoms that may include fever, loss of appetite, extreme fatigue, and pain on the right side of the abdomen. But most people carry the virus for years without ever noticing any symptoms. Many don't know they have HCV until they are tested.

Some people, in fact, never develop clinical signs or symptoms of liver disease. Though they have been infected with the virus, their liver enzyme levels remain normal. At the other end of the spectrum are people with high levels of the virus in their blood, abnormal liver enzyme levels, and signs of serious liver damage. In between are people with mild symptoms or moderate elevation of liver enzymes. But even with mildly abnormal liver enzymes, most people feel just fine.

In the majority of people infected with hepatitis C, symptoms don't show up until the second or third decade after infection. By then, unfortunately, the virus has usually damaged the liver. That's why it's important for anyone who believes he or she may have been exposed to hepatitis C to see a doctor and ask about getting tested.

Early Symptoms

Early symptoms of hepatitis are easily confused with those of other illnesses. They include such common complaints as the following:

During a physical examination, doctors may notice mild enlargement of the liver. Some patients also develop unusual reddening of the palms of the hands, called palmar erythema.

Later Symptoms

If the virus begins to cause damage to liver cells, more severe symptoms may appear. These include:

Sometimes the effects of HCV extend beyond the liver. These conditions are called extrahepatic, or "outside the liver." Many are caused by the immune system's response to the virus. These conditions include:

Since hepatitis C can also do silent damage to your liver, it's important to get tested if you have one or more risk factors for the disease.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, G.L., et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pg. 41-52

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated August 11, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

DIAGNOSIS

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Hepatitis C viruses are so small that they can only been seen with the most powerful electron microscopes. Yet simple tests can reliably tell whether someone has been exposed to the virus. Other tests can show if someone still has an active infection. Still other tests are able to gauge the extent of damage to the liver.

Often the first sign that something is wrong comes from a standard blood test, which includes a test for enzymes associated with liver function. An abnormal reading alerts doctors to the possibility of liver disease. Several other tests performed by analyzing blood can verify the presence of the hepatitis C virus. One simple test measures signs of antibodies to hepatitis C, small molecules produced by the immune system when it detects a virus. Other tests measure the level of viruses found in the blood and identify precisely which type of hepatitis C is present. The most common tests for hepatitis C include the following:

Enzyme immunoassay

This test detects antibodies to hepatitis C, sometimes called anti-HCV. Antibodies are the tiny molecules the immune system produces when it encounters foreign germs. Even after an infection is over, antibodies often remain in the bloodstream for years. Thus an antibody test can show if someone was exposed to a particular virus, even if the exposure occurred years earlier. The molecules produced to combat hepatitis C have a different shape from antibody molecules produced to thwart hepatitis A, for instance. For that reason, antibody tests are also very specific. They can determine exactly what type of hepatitis a person carries.

The anti-HCV test used today is called EIA-3, because it is the third generation of such tests. It is more specific and sensitive than previously used tests. But it isn't perfect. Sometimes it mistakenly detects antibodies when there aren't any (a false positive reading). Or it can fail to detect antibodies even when someone does have the hepatitis C virus (a false negative). False negatives can occur in people with weakened immune systems that can't produce enough antibodies for detection with EIA. Doctors typically confirm EIA-3 tests using another detection method, such as an RNA test (see below).

HCV RNA

The HCV RNA test looks for the presence of the genetic material that makes up the hepatitis C virus, called RNA. One of two different kinds of methods may be used: polymerase chain reaction (PCR) or transcription mediated amplification (TMA). Unlike an antibody test, which looks for signs that the immune system has responded to hepatitis C, the RNA test looks for the presence of the virus itself. Finding HCV RNA is a reliable way to demonstrate that HCV infection is present.

HCV RNA testing is often used for immunocompromised patients, meaning those whose immune systems may not be able to generate antibodies against the virus. It is also sometimes used for patients exposed to the virus only very recently, whose immune systems may not have had time to generate an antibody response. Doctors also use HCV RNA tests when patients have signs of liver disease but test negative for antibodies.

In patients with confirmed hepatitis C infection, viral load tests can measure the amount of virus found in blood. Viral levels do not necessarily mean a more serious disease or a bad prognosis. But knowing a patient's virus level can help predict how he or she will respond to medication. People with low levels of HCV respond better to alpha interferon and ribavirin, for instance, a combination of drugs often prescribed to treat hepatitis C. Monitoring HCV RNA levels can also provide a measure of how well treatment is working.

Unfortunately, tests that measure viral load are inexact. Different methods used by different laboratories can yield results that are sharply at variance, even when testing material from the same blood sample. What's more, levels of HCV in the blood go up and down on their own by a factor of as much as 10.

Recombinant immunoblot assay

Also called "Western blots," recombinant immunoblot assays are frequently used to confirm HCV antibody tests. For this test, blood is exposed to strips that are treated with proteins from the hepatitis C virus. A change in color indicates that antibodies from the blood have attached to the viral proteins. This shows that the immune system has responded to an infection by generating anti-HCV antibodies. If two or more proteins change color, the test is positive. If only one changes color, the results are considered indeterminate. Doctors may repeat the test, or use another test.

Genotype tests

Another useful test determines the precise form of HCV in the blood. There are six known genotypes, or genetically distinct types, and more than 50 subtypes of hepatitis C. Researchers do not understand all the ways in which these genotypes and subtypes differ. But it is clear that some genotypes respond better to antiviral treatments than others. Patients with genotypes 2 and 3, for example, are two to three times more likely to respond to interferon therapy than patients with genotype 1. Doctors typically prescribe a longer course of treatment, with higher doses of antiviral drugs, to patients infected with genotype 1.

Liver biopsies

By examining tissue taken from the liver, doctors can gauge the severity of damage to the liver. Infection with hepatitis C virus causes several characteristic changes to liver tissue, including inflammation, death of liver cells, and fibrosis (the development of scar tissue).

Doctors typically describe the extent of inflammation and cell death on a scale of none, minimal, mild, moderate, or severe. Fibrosis is typically ranked on a scale of 0 to 4, depending on how widespread it is in the liver.

Liver biopsies are invasive procedures that carry a small but real risk of complications. These include infection, bleeding, and damage to nearby organs. Some patients experience pain that requires medication after undergoing a liver biopsy.

Other tests used to diagnose HCV

Infection with hepatitis C virus can cause a number of telltale changes in levels of enzymes and other factors measured in the blood. These changes are sometimes the first sign that something is wrong. They can also be used to confirm a diagnosis and determine disease progress. Here are some of the biochemical markers that doctors measure:

Why so many tests?

When doctors suspect hepatitis C infection, several tests are often prescribed to confirm a diagnosis and determine the condition of the liver. The particular tests your physician recommends will depend on what information he or she needs. When doctors suspect a case of acute hepatitis C, for instance -- based on risk factors for the disease along with symptoms such as jaundice, fatigue, and nausea -- they often measure serum alanine transferase. Levels of this enzyme frequently increase tenfold or more in acute hepatitis C.

In as many as four out of 10 patients, anti-HCV is not detected until two to eight weeks after symptoms show up. For this reason, a test for HCV RNA is often performed. Because it detects the genetic material of the virus itself, it is more effective at detecting an early infection than antibody tests. Alternately, doctors may simply wait for a month and do another anti-HCV test.

In about 75 percent of people infected with hepatitis C, the infection becomes chronic. Chronic hepatitis C is diagnosed when the anti-HCV antibody test remains positive and liver enzyme levels remain elevated after six months. To confirm chronic hepatitis C, doctors often use the HCV RNA test to determine if viruses are present in the blood.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, G.L., et al. Hepatitis C virus infection. New England Journal of Medicine, July 5, 2001, pp 41-52 Seeff et al. The National Institutes of Health Consensus Development Conference management of hepatitis C. 2002, Clinical Liver Disease, Feb 2003, pp 261-87

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

WHAT CAN I DO TO PROTECT MY LIVER?

Topics:

If you've been diagnosed with hepatitis C, there is plenty you can do to stay healthy and lower your risk of developing serious liver disease. Like many diseases, hepatitis C is affected by the way we live -- what we eat, how much we exercise, even how we deal with stress. The healthier you are overall, the better your body can deal with the virus. The less strain you put on your liver, the healthier it will remain.

That doesn't mean you can get rid of the virus by living right or that people who develop serious liver disease as a result of HCV did something wrong and are somehow responsible. Many factors combine to determine the course of the disease. But living a healthy lifestyle can keep you stronger and better able to deal with the effects of the disease and treatment. A healthy lifestyle can also improve the overall quality of your life. Here are the six most important steps:

Eat well

Most of the substances we ingest eventually find their way to the liver. Part of its job is to remove toxins and metabolize substances for use by the body. So it makes good sense that eating a healthy diet will help keep your liver strong.

Most of the advice is valid whether you're infected with HCV or not. The Centers for Disease Control and Prevention guidelines recommend eating a well-balanced, low-fat diet. A well-balanced diet includes plenty of fruits and vegetables (five to nine servings a day), whole grain breads and cereals, and lower-fat sources of protein, such as lean meats. Saturated fat, the kind found in meat and dairy products, has been shown to clog arteries and lead to cardiovascular disease.

Lately, scientists have discovered that trans fats (also called hydrogenated fats) may be just as bad or worse for the arteries. And some experts believe that these artificially made fats may be especially difficult for the liver to metabolize. To reduce your intake of trans fats, cut back on processed foods, which are the main source of trans fats. Examples include chips, cookies, and crackers.

Another important aspect of a healthy diet is eating just enough to maintain a healthy weight. Doctors are alarmed at the expanding waistlines of Americans: Overweight and obesity have been linked to a long list of health problems, including diabetes and heart disease. There is some evidence that if you're HCV-positive and overweight, shedding some pounds could help your liver.

A study reported in the American Journal of Clinical Nutrition put 19 overweight people with hepatitis C on a 12-week diet and exercise program. The participants lost 13 pounds on average, about a pound a week. At the same time, several markers of liver health improved, including liver enzymes and the amount of scar tissue and fat in the liver.

Avoid alcohol

People with hepatitis C should eliminate alcohol from their diet, according to the Centers for Disease Control and Prevention. Several studies have shown that among people with hepatitis C, regular drinkers have higher levels of the virus than do nondrinkers. Studies also show that when people with HCV infection stop drinking alcohol, their virus levels decrease.

Now, for the first time, experts are finding out why. In an experiment directed by Wen-Zhe Ho, MD, director of retroviral research at Children's Hospital of Philadelphia, researchers discovered that alcohol causes hepatitis C viruses to multiply in the liver. The findings, reported in 2003 in the journal Hepatology, show that alcohol increases the activity of a protein that triggers HCV to make new copies of itself. These new copies speed the progress of the infection and raise the risk of liver damage.

Some experts still debate whether it's safe for people with HCV to drink small amounts of alcohol -- a glass of wine or beer a day, for instance. Several studies suggest that the biggest danger comes from excessive intake. But other research has shown that even small amounts of alcohol can put a strain on the liver and increase the risk of damage. For advice on what's right for you, talk to your doctor. If you have a problem with alcohol, or if someone you know needs help, you can find out about local treatment programs in your community by calling the National Drug and Alcohol Treatment Referral Routing Service at 1-800-662-HELP.

If you smoke, make a plan to quit

Tobacco is well known to increase the risk of many cancers, of course. But the toxins in cigarette smoke can also harm the liver. Studies have shown that people with hepatitis who smoke run an increased risk of developing both cirrhosis of the liver and liver cancer. A 2003 study by researchers at the Nagoya City University Medical School in Japan found that habitual smoking more than doubled the risk of liver cancer among people infected with the HCV. A study by French researchers published the same year showed that smoking also dramatically increases the risk of cirrhosis.

It's easy to advise someone to quit smoking, of course -- it's much harder to quit. Quitting may be especially difficult for anyone who is being asked to make other lifestyle changes, such as giving up alcohol and other drugs. The stress of dealing with hepatitis C can also make it hard to stop smoking. But many people do successfully quit. Nicotine patches, gum, and other aids can make it easier. Support groups are available in many communities. You'll find useful resources by contacting these Web sites:

www.surgeongeneral.gov/tobacco

www.lungusa.org

www.quitnet.com

Stay active

There is no direct evidence that physical activity helps battle hepatitis C viruses. But there is good reason to think that regular moderate exercise keeps the immune system in good working order. Regular exercise also keeps the heart strong and the cardiovascular system robust, which is important to overall good health. What's more, regular exercise helps many people relieve stress and feel better about themselves. That's particularly important when you're dealing with a medical condition like hepatitis C.

Even patients who have received liver transplants, new research shows, can benefit from moderate activity. A study by researchers at the University of California at San Francisco found that liver transplant recipients who participated in regular physical activity enjoyed a higher quality of life.

Relax and recharge

One of the biggest complaints for people with HCV infection is fatigue. When you're feeling wiped out, it's important to relax and recharge your energy. It's not always easy to find time for this if you have a lot of demands on you. But taking just 15 minutes to sit quietly and relax can make a big difference in how you feel. Another useful way to relax is to do something that you love: reading, listening to music, talking to a close friend, pursuing a favorite activity.

Taking time out to relax can also help you ease the inevitable stresses that come from dealing with a health problem like hepatitis C. There is no direct evidence that stress worsens the prognosis for people with HCV, but there is plenty of evidence that stress can weaken the immune system. Stress can also take the joy out of life, so it's important to find ways to relax and let off steam.

Talk to your doctor before starting any pills, including vitamins or supplements

Many medications and other substances are processed and broken down by the liver. But some of them can be toxic to this hard-working organ. In fact, drug-induced liver injury is now the leading cause of acute liver failure in the United States, more common than all other causes combined. Nearly 1,000 drugs are believed to harm the liver, including over-the-counter drugs, some vitamin and mineral supplements, prescription drugs, illicit recreational drugs, and even herbal remedies. In 2002 the FDA warned about liver toxicity associated with kava kava, for instance. Ephedra, mistletoe, and comfrey have also been associated with liver toxicity.

All these substances can be especially harmful if you have chronic hepatitis C. Because of the infection, you may have abnormally low levels of certain enzymes that are needed to break down toxins. Or you may have impaired blood flow, which means substances will remain in the liver longer than normal.

The list of potentially harmful drugs, medications, and supplements is long and constantly being updated, so don't take any pills or potions before talking to your health care provider. Make sure your doctor is aware of all medications, over-the-counter drugs, supplements, or herbal remedies you are currently taking.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Painter, P. et al. Physical activity and health-related quality of life in liver transplant patients. Liver Transplants, March 2001, pp 213-19.

The American Liver Foundation. Diet &your liver. www.liverfoundation.org

Ho, W. et al. Alcohol increases hepatitis C virus in human cells. Hepatology, July 2003, pp 57-65

Pessione, F. et al. Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking, and abstinence. Liver International, Feb 2003, pp 45-53

Vento, S. et al. Does hepatitis C virus cause severe liver disease only in people who drink alcohol? Lancet Infectious Diseases, 2002, pp 303-309.

Koide, T. et al. HBV/HCV infection, alcohol, tobacco, and genetic polymorphisms for hepatocellular carcinoma in Nagoya, Japan. Asian Pacific Journal of Cancer Prevention, 2000, pp 237-243

Thomas, D.L. et al. The natural history of hepatitis C virus infection: host, viral and environmental factors. Journal of the American Medical Association, July 26, 2000, pp. 450-6

HCV Advocate, newsletter. Hepatitis C and smoking. February 2003

HCV Advocate, newsletter. Drugs and the liver. May 2003

HCV Advocate, newsletter. Diet and hepatitis C. April 2003.


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated October 29, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

DIFFERENCES BETWEEN ACUTE AND CHRONIC HEPATITIS C

Topics:

The difference is a matter of time. An acute infection occurs soon after someone is exposed to a germ, such as the hepatitis C virus (HCV). If the immune system is unable to fight off the infection, the disease becomes chronic.

What are the symptoms of acute hepatitis?

The onset of acute hepatitis C is usually silent, but may be marked by malaise, nausea, and yellowing of the skin and eyes (jaundice).

In about 20 percent of HCV infections, the immune system successfully eliminates the virus and patients fully recover. In the other 80 percent, the virus persists. However, people who have a chronic infection may live for years without experiencing any symptoms at all. Severe complications and death from the infection usually only overtake those who also develop cirrhosis. (This occurs in 15 to 20 percent of people with chronic hepatitis C.)

How is chronic hepatitis diagnosed?

Doctors typically diagnose chronic hepatitis when blood tests show active virus and elevated liver enzymes for longer than six months. Chronic infections are dangerous because the virus can continue to invade and destroy liver cells. Often the immune system's unsuccessful attempts to get rid of the virus cause unintended damage to nearby tissues.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, GL, et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Centers for Disease Control. Hepatitis C FAQs for the Public. July 2008. www.cdc.gov/hepatitis/C/cFAQ.htm#cFAQ04


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

WHAT TO EXPECT OVER TIME WITH HEPATITIS C

Topics:

Very understandably, almost everyone diagnosed with the hepatitis C virus asks the same question: "What's going to happen to me?"

Unfortunately, with HCV infection, it's very hard for doctors to offer an answer. More than with most diseases, the course of HCV infection varies widely from person to person. In about 15 to 25 percent of people infected with the virus, their immune systems attack the virus and eliminate it, and they never know they were exposed. At the other extreme are people who develop chronic infections and eventually serious liver disease. In between are people who carry the virus but never show signs of trouble, and others who have mild symptoms and some liver damage, but never develop serious illness.

Many factors affect the course of HCV infection

How can one virus act so differently in different people? Researchers don't know all the answers. They do know that men are more likely to develop serious liver problems than women. A study published in 2003 found that 13 to 46 percent of men developed cirrhosis (scarring of the liver) over a 30-year period of being infected with HCV. Only 1 to 29 percent of women developed the disease during the same period.

The age when infection occurs also makes a difference in the course of the disease. The earlier in life people are infected, the lower the risk of serious complications from hepatitis C infection.

Other health problems and HCV infections

Co-infections with other viruses can worsen the prognosis for HCV. Many people are co-infected with hepatitis C and HIV/AIDS. Both viruses are spread through sharing needles. In a large European study, 33 percent of HIV-positive patients were shown to be infected with HCV as well. When experts looked just at known injection-drug users, they found that 75 percent of HIV-positive patients also had hepatitis C virus. Being infected with these two viruses appears to increase the risk of cirrhosis. In 2008, researchers found that after 20 years of infection, the risk of developing cirrhosis was 21 percent in people who carried both HCV and HIV and 16 percent for those infected only with HCV.

Certain lifestyle aspects also shape the course of HCV infection. People who are infected and who consume alcohol are more likely to develop liver problems than are nondrinkers. Alcoholics are at the highest risk. A study by University of Pennsylvania researchers found that alcohol actually causes the hepatitis C virus to multiply faster. Alcohol also lessens the effectiveness of alpha interferon, which is used to treat serious HCV infections. In a 2002 report, Italian researchers showed that alcohol increases oxidative stress in the liver, generating unstable free radicals that can damage liver cells. The scientists speculate that "oxidative injury might be one of the mechanisms by which alcohol contributes to the progression of chronic hepatitis C."

Other researchers have found a connection between hepatitis C infection and type 2 diabetes and obesity. In 2009, scientists from the Center for Liver Diseases at Inova Fairfax Hospital analyzed health data from almost 16,000 people, including some with hepatitis C. According to the study results, obesity and type 2 diabetes were associated with a higher mortality rate in patients with hepatitis C. This finding suggests that making lifestyle changes to ward off obesity and diabetes should be an important consideration for people with hepatitis C.

Surprisingly, the level of virus in the blood, called viral load, doesn't help predict the course of hepatitis C. Some people with high viral levels do well. Others, with low levels of virus, develop liver problems. Doctors use the test to gauge how well treatment is working, but not to make a prognosis. Elevated levels of aminotransferase, a liver enzyme, are a sign that the disease is causing liver damage. But even this marker isn't a perfect predictor. As many as 30 percent of patients with liver damage have normal levels of aminotranferase.

A look at the numbers

When patients ask, "What will happen to me?" the best answer doctors can give is to explain how the disease progresses in an average group of patients. Of every 100 people infected with HCV:

As those numbers show, most people infected with hepatitis develop chronic infections. Among them, most have some signs of liver damage. But the numbers are also reassuring. Fewer than 7 percent of those with chronic hepatitis C die of complications from the virus. That means that for a large majority of people, the virus isn't fatal. In many, it causes nothing more than mild symptoms such as fatigue.

The changing picture of HCV infection

There's more good news coming out of clinical trials and pharmaceutical laboratories. The combination treatment used today is more effective than anything doctors were able to offer when the disease emerged in 1989. Combination therapy can eliminate the virus in about half of all patients. Some combination treatments can do even better. One 2007 study of nearly 1,000 hepatitis C patients showed a cure rate of 99 percent after treatment with peginterferon and ribavirin -- with a number of patients remaining disease-free for as long as seven years. The prognosis for people infected with HCV is brighter than ever. And it's likely to get even brighter as doctors learn more effective combinations of existing drugs and as new drugs are developed.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, GL, et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Ho, W et al. Alcohol increases hepatitis C virus in human cells, Hepatology, July 2003, pp 57-65

Pessione, F et al. Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking, and abstinence, Liver International, Feb 2003, pp 45-53

Seeff et al, The National Institutes of Health Consensus Development Conference management of hepatitis C 2002, Clinical Liver Disease, Feb 2003, pp 261-87

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Thomas DL et al, The natural history of hepatitis C virus infection: host, viral and environmental factors, Journal of the American Medical Association, July 26, 2000, pp. 450-6.

Quaglio GL et al, Hepatitis C virus infection: prevalence, predictor variables and prevention opportunities among drug users in Italy, Journal of Viral Hepatitis, Sep 2003, pp 394-400.

Hisada et al, Increased hepatitis C virus load among injection drug users infected with HIV and HTLV2, Journal of Infectious Diseases, Sept 15, 2003, pp 891-7 Sanchez-Quijano et al, Influence of human immunodeficiency virus type 1 infection on the natural course of chronic parenterally acquired hepatitis C, European Journal of Clinical Microbiology and Infectious Disease, Nov 1995, pp 949-53.

American Medical Association. Cure rates becoming the norm for patients with hepatitis C. June 2007. www.ama-assn.org/amednews/2007/06/18/hlsc0618.htm

National Digestive Diseases Information Clearinghouse. Chronic Hepatitis C: Current Disease Management. November 2006. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/

Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis c virus infection: A meta-analysis and meta-regression. Hepatology. August 2008; 48(2): 418-431.

Thein HH, Yi Q, Dore GJ, Krahn MD. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of antiretroviral therapy: a meta-analysis. AIDS. October 1, 2008; 22(15).

Centers for Disease Control. Hepatitis C: FAQs for the Public. July 2008. www.cdc.gov/hepatitis/C/cFAQ.htm#cFAQ25

Younossi ZM, McCullough AJ. Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: impact on disease progression and treatment response. Liver International. 2009 Apr;29(4):617.


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated September 28, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HEPATITIS C AND LIVER DISEASE

Topics:

The word hepatitis is derived from Greek -- "hepar" meaning liver, and "-itis" the suffix meaning inflamed or diseased. The causes of hepatitis range from chronic alcoholism to chemical toxins. In addition, at least six different viruses that cause the disease have been identified. The most prevalent chronic infection in the United States is due to hepatitis C.

Why do certain viruses target the liver? To begin with, almost all viruses target specific tissues in the body. Cold and flu viruses invade cells of the respiratory tract. Polio viruses strike nerve cells. HIV attacks key immune cells. Similarly, the natural target for the hepatitis C virus and other hepatitis viruses is liver cells, because molecules on the surface of liver cells match corresponding molecules on the surface of the viruses.

Turning liver cells into virus factories

Once inside a healthy cell, the hepatitis C virus (HCV) inserts its own genetic code into the genes of the cell, and, like an enemy invader, takes control. The virus shuts down the cell's normal functions and begins to use the cell to create new viruses. These newly formed viruses wrap themselves in pieces of the cell's outer wall before breaking free to infect other cells.

Researchers used to believe that only a small percentage of liver cells became infected with the virus. However, more recent studies show that 50 percent or more liver cells can harbor the virus. HCV is also an extremely robust virus: Scientists estimate that an infected individual can produce 10 trillion new viruses in a single day.

How does the hepatitis C virus cause disease? First, cells invaded by the virus stop functioning normally. These injured cells begin to leak an enzyme called alanine aminotransferase, or ALT. Rising levels of ALT in the bloodstream are often the first sign of liver damage. Eventually, the disruption caused by surging swarms of new viruses destroys invaded cells.

Meanwhile, the immune system struggles to fight the infection and causes inflammation in the liver, which further damages healthy liver cells. Tiny scars form as the liver tries to repair itself, in much the same way that skin heals after being injured. Unfortunately, when the infection becomes chronic, more and more scar tissue is created in a process called fibrosis. Eventually the scar tissue knits together and begins to interfere with normal liver function. Knots of this scar tissue, or nodules, form as large areas of the liver become scarred.

Slowly, more and more of the liver's normal functions become impaired, causing the condition called cirrhosis. Blood no longer flows normally through the organ because the main vein that supplies blood to the liver can become restricted and even blocked. As the disease advances, the normally smooth and firm organ shrinks and becomes hard. The liver begins to fail when it becomes unable to filter toxins, drugs, or wastes from the blood, and can no longer produce the clotting factors necessary to stop bleeding. At this point, fluid builds up in the abdomen and legs and there may be bleeding in the intestines.

Hepatitis and liver cancer

In some cases, hepatitis C infection can also lead to liver cancer. In absolute numbers, new cases of liver cancer are on the rise in the United States: The incidence of liver cancer has climbed from 1.4 people in every 100,000 during the 1970s to 6.4 per 100,000 between 2001 and 2005. Today, researchers attribute the increasing number of liver cancer cases to an increasing population and note that the disease has stabilized. The American Cancer Society estimates 22,620 new cases in 2009, mostly in men, with an average age of 65.

Experts say one major reason for the increase is the surge of HCV infections that began in the 1960s. That surge came about in part when the virus entered the blood supply and began to be spread through transfusions. Another reason may be the rise in hepatitis B infections, which can also lead to liver cancer. (HIV/AIDS infection also increases the danger of liver cancer.)

Scientists are only beginning to understand exactly how hepatitis C virus causes cancer. The invading virus's genes disrupt the genes of healthy liver cells. Some of the genetic changes that occur interfere with normal signals that control how cells grow. Scientists suspect that the virus's ability to stimulate cell growth may explain why infection sometimes leads to liver cancer because cancer is a disease of runaway cell growth. Researchers have recently discovered that hepatitis C viruses can also stimulate liver cells to reproduce. This strategy creates more cells for the virus to invade, and it may also set the stage for cancer.

The future toll

Developing cirrhosis or liver cancer can take 20 to 30 years, or even longer. Medical experts predict that cirrhosis and liver cancer will take a growing toll in years to come, even though the number of new HCV infections is declining. In a 2003 analysis, scientists at Baylor University Medical Center calculated that the proportion of people infected with the virus who develop cirrhosis could increase from 16 to 32 percent by 2020. The incidence of liver cancer could climb by 81 percent, and liver-related cancer deaths could jump by 180 percent.

Although these statistics are frightening, most infections with hepatitis C do not advance to liver failure or liver cancer. What's more, new treatment options are already improving the prognosis for people with hepatitis C. It's also worth remembering that people infected with the virus can improve their odds of staying healthy by avoiding alcohol and following the appropriate drug regimen. For example, combined treatment with alpha interferon and ribavirin has been shown to arrest hepatitis C in more than half (and in some studies, nearly all) of patients treated, dramatically reducing the danger of future complications.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Davis, GL. et al. Projecting future complications of chronic hepatitis C in the United States, Liver Transplantation, Apr 2003, pp 331-8.

Hashem, B. et al. Dramatic rises in the incidence of hepatocellular carcinoma in the United States, abstract, Digest Disease Week Conference 2003.

Lauer, M et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

National Digestive Diseases Information Clearinghouse at digestive.niddk.nih.gov

American Cancer Society. What Are the Key Statistics About Liver Cancer? May 2007.

American Cancer Society. How many people get liver cancer? May 2007.

American Medical Association. Cure rates becoming the norm for patients with hepatitis C. June 2007. www.ama-assn.org/amednews/2007/06/18/hlsc0618.htm


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

YOUTH AND HEPATITIS C

Topics:

Hepatitis C, sometimes known as the "silent epidemic," can attack the liver over a period of years or even decades before its unwitting victims realize they've been infected. Until recently, this potentially fatal disease was all but unknown, making it a mystery to both its victims and the public at large.

Today, however, most of us have seen at least one news report about the virus that now infects nearly an estimated 4 million Americans -- or five times the number of people infected with HIV. Many baby boomers raising children of their own -- and warning them to avoid hard drugs -- have been horrified to learn that their own all-but-forgotten teen-age experiments with injectable drugs left them infected with the hepatitis C virus.

But what about the young people who make up the bulk of new infections today? In 2007, according to the Centers for Disease Control and Prevention (CDC), about 17,000 people were newly infected with HCV, the virus that causes hepatitis C. Although many older folks got hepatitis C from contaminated donated blood (the national blood supply wasn't screened for the disease until 1992), most new infections are occurring among young adults (20-39 years old) and injection drug users, according to CDC data.

A lifesaving tattoo?

Among the young people grappling with the disease is 20-year-old Winnifred Pitts, who learned she had hepatitis C in 2001. By then, she had already been shooting heroin for two years. "I only shared needles a couple of times with a couple of different boyfriends," she says. "But they were both junkies, so I probably got it from one of them."

Pitts ran away from home at age 14 and lived on the streets in Eugene and Portland, Oregon, and in Tucson, Arizona, over the next several years. She ended up back in Eugene at a drug rehabilitation center in 2001. It was there, while she was withdrawing from heroin, that doctors told her she had hepatitis C.

Young people living on the street, such as Pitts, are more likely than other teen-agers and young adults to use injectable drugs -- and consequently, to contract hepatitis C. One Portland study found that homeless youths who used injection drugs were nearly 10 times more likely than the average American to have either hepatitis C or B. (Hepatitis B is also spread through shared needles, but it can be contracted through sex much more easily than hepatitis C.)

Other young adults may increase their risk of the disease if they use injection drugs or get body piercings or tattoos with unsterilized needles. (Although tattoos and piercings are not classified as an official risk factor for hepatitis C, the Centers for Disease Control and Prevention note that they can be risky if they're performed with dirty or blood-stained tools.) Youths -- and everyone else -- may also be at slightly greater risk for hepatitis C if they have unprotected sex with multiple partners, according to the CDC, and may be at greater risk if they snort drugs like heroin, cocaine, or methamphetamine ("crystal meth").

For her part, Pitts is doing better these days. She works part-time as a tree-trimmer in Eugene and is sharing an apartment with friends. However, the young Oregonian is still fighting her addiction. Her body still craves heroin, and she had a relapse a few weeks ago. Despite medical advice that she should stay away from alcohol, fighting her drinking problem has also been a struggle. "Now I only drink like one night a week," says Pitts. "That's about the best I can do right now."

For now, Pitts tries to eat a low-fat diet, does kickboxing and yoga for exercise, and is focusing on getting back on her feet. Worried at the way her liver aches when she drinks, she occasionally goes to a doctor to have her liver enzymes measured. (One test she undergoes is known as the ALT test; it looks at the enzyme alanine aminotransferase, or ALT, which is found in significant concentrations in the liver. The enzyme should be found inside liver cells and in very small concentrations in the blood; when blood levels are high, this suggests possible liver damage.) Her levels are high, but she's not really sure what that means. Besides, Pitts confesses, she didn't have enough money to pay her health insurance premium recently, so now she doesn't go to the doctor at all.

One thing Pitts is adamant about is making sure she doesn't infect anyone else with hepatitis C: She had "HCV" tattooed in large block letters across her stomach last year. "I think everyone should get their STDs and stuff tattooed on them," says Pitts, "because otherwise they don't tell anyone and they pass them onto other people."

Widespread ignorance

Of course, for every youth like Pitts, there are many more who may be spreading the virus unwittingly. The good news is that HCV infections have decreased dramatically over the past decade. New infections dropped from an estimated high of 291,000 cases per year in 1989 to an estimated 17,000 in 2007. According to the Centers for Disease Control and Prevention (CDC), most of the decline occurred among injection drug users, perhaps because of safer injection practices brought about by HIV prevention programs and needle-exchange programs around the country. The challenge today is twofold: to keep bringing the number of new infections down each year; and to get those who have the virus diagnosed and under a doctor's care.

"The awareness of hepatitis C today is about at the level of HIV awareness in 1985," says Jarvis Allen, supervisor of the Yellow Brick Road outreach program for homeless youth in Portland, Oregon. The majority of homeless youth with HCV exhibit no symptoms, and many don't even know they're infected. Those who do know they have the disease often don't understand how it is spread, and may not think it's serious enough to change their lifestyles.

"They're just thinking, 'Hey, I've got a place to sleep tonight, I got something to eat, I got friends down here, and maybe I even got drugs. Life is good,' " Allen says.

Allen's organization is working hard to change those misconceptions. It reaches out to thousands of homeless youths every year, offering blankets, food, and counseling to those they find sleeping under bridges and in parks. Equally important, the program also directs at-risk youth to the nearby free medical clinic Outside In, which offers screening and treatment for hepatitis C.

Allen also advises all parents to sit down with their teenagers and have "the talk" about injection drugs and hepatitis C. "Chances are they already know someone who uses IV drugs, and these kids don't think twice about the deleterious health effects of what they're doing," says Allen. "There's no sense trying to shelter kids from this anymore."

-- Paige Bierma is a health and medical writer who has contributed to Hippocrates, Safety + Health magazine, and Vibe.

Further Resources

National Center for Infectious Diseases
Centers for Disease Control and Prevention
Hepatitis C Page
888/4-HEP-CDC (443-7232)
www.cdc.gov/ncidod/diseases/hepatitis/c/index.htm

American Liver Foundation
75 Maiden Lane, Suite 603
New York, NY 10038
800/GOLiver (465-4837) or 888/4 HEP USA (423-7872)
www.liverfoundation.org

Hepatitis Central
A national Web site that lists support groups by state and provides hundreds of articles about hepatitis.
www.hepatitis-central.com

References

Interview with Winnifred Pitts, Eugene, Oregon.

Interview with Jarvis Allen, Yellow Brick Road, Portland, Oregon.

Injection Drug Use in a Homeless Adolescent Population. Oregon Research Institute. 2001.

Viral Hepatitis C: Frequently Asked Questions. National Center for Infectious Diseases, Centers for Disease Control. Feb. 13, 2003. www.cdc.gov/ncidod/diseases/hepatitis/c/faq.htm

Centers for Disease Control. Viral Hepatitis C. December 2006. http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm

C. Everett Koop Institute. Hepatitis C: The Epidemic. http://www.epidemic.org/theFacts/theEpidemic/

National Institute of Allergy and Infectious Diseases. HIV Infection and AIDS: An Overview. October 2007. http://www.niaid.nih.gov/factsheets/hivinf.htm

Centers for Disease Control. FAQs for Health Professionals: Hepatitis C. July 2008. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1

Centers for Disease Control. Viral Hepatitis Statistics. 2009. http://cdc.gov/hepatitis/statistics.htm


Reviewed by Joshua Rassen, MD, FACP, a board-certified internist and geriatrician with a practice in San Francisco.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HOW IS HEPATITIS C TREATED?

Topics:

Dramatic advances have been made in the treatment of hepatitis C since the virus that caused it was first identified in 1989. The current treatment for most patients is a combination of two drugs: pegylated alpha interferon and ribavirin. Together, these two drugs have been shown to slow or stop the progress of hepatitis C in some, but not all, patients. Although far from perfect treatments, they offer new hope to people with the disease.

Pegylated interferon (peginterferon)

Alpha interferon is a substance produced by the immune system in response to viral infections. Researchers have developed techniques to synthesize alpha interferon that can be used as a drug. The newest form has been chemically modified by the addition of a molecule of polyethylene glycol. The process -- pegylation -- creates a form of alpha interferon, called peginterferon that remains in the blood longer. Levels of peginterferon in the blood are also much more constant than those of previous forms of alpha interferon. For that reason, pegylated interferon can be administered as an injection just once weekly. The new form of the drug is also better than previous forms at inhibiting the hepatitis C virus. More patients respond to peginterferon than previous forms of synthetic alpha interferon.

Ribavirin

Ribavirin is an antiviral drug given in pill form. It acts against a variety of viruses, including herpes and influenza. Alone, it has little effect against the hepatitis C virus. But the combination of ribavirin and peginterferon has been shown to produce an antiviral effect two to three times more powerful than peginterferon alone. Ribavirin is typically given twice a day in 200-mg capsules. The total dose is based on a person's body weight. Someone who weighs 145 pounds, for example, is given 1000 mgs.

Combination therapy (peginterferon and ribavirin)

For patients treated with the combination of peginterferon and ribavirin, the length of treatment depends on the genotype of the virus. Patients with genotype 1, the most common form found in the US, are usually given the drugs for 48 weeks. Those with genotypes 2 and 3 usually respond better to the combined treatment, and are typically given the drugs for 24 weeks. The optimal dose of ribavirin also varies depending on genotype. Patients with genotypes 2 and 3 are typically prescribed a dose of 800 mg, while those with genotype 1 typically receive 1000-mg doses.

Some patients shouldn't receive peginterferon. These include people with autoimmune hepatitis or liver disease in which the liver is starting to fail, or those who have had an allergic reaction to alfa interferon in the past, or to products derived from E. coli.

An important caution about both alpha interferon and ribavirin: They can cause serious complications in pregnant women and severe birth defects. Birth control is essential for both men and women taking these drugs. Neither pregnant women nor the female partners of men on this therapy should take these drugs, and both groups should be extremely careful to avoid becoming pregnant for six months after the therapy is discontinued. Male partners of pregnant women should not take these drugs, either.

In addition, some patients cannot tolerate ribavirin because the drug can cause dangerous reactions in people with kidney disease or serious heart disease. In this case, pegylated alpha interferon alone is recommended for a period of 48 weeks.

How well do the treatments work?

In seven out of 10 patients, the hepatitis C virus can no longer be detected (using HCV RNA blood tests) after treatment is completed. Liver enzyme levels return to normal. In some patients, the virus begins to multiply again once treatment is stopped, but 55 percent of patients given combination therapy have a sustained response. That is, the virus remains undetectable for six months or more after treatment is stopped. About 35 percent of patients given alpha interferon alone have a sustained response.

Are there side effects to treatment?

Yes. Like almost all effective treatments, the drugs used against hepatitis C have side effects and complications. Most are mild to moderate in severity, and can be managed by your doctor. Side effects are typically the worst after the first injection and during the first few weeks of treatment.

Side effects of combination therapy that occur in 10 percent or more of patients include:

Are there other treatments for hepatitis C?

Yes. Other treatments include interferon alone, standard interferon plus ribavirin, and standard interferon plus amantadine. These drugs are sometimes used to treat people whose infection has relapsed, or who don't respond to the peginterferon and ribavirin combination therapy.

Recent research on a hepatitis C-specific protease inhibitor called telaprevir forecasts a new era in the treatment of this disease. In April 2009, the New England Journal of Medicine reported on a study that showed significant improvement in the chances of being cured when telaprevir was added to the current standard therapy, and treatment took only half the time. If further studies confirm these results, telaprevir could soon be approved by the Food and Drug Administration.

A closer look at hepatitis C treatment and depression

In some cases, side effects can be severe enough to force people to stop taking the medications. In a 2003 study of 39 patients with life-threatening liver disease, for instance, one in three people became so depressed after several months of interferon therapy that they stopped taking their medication. The depression showed up suddenly and at almost the same time in most of the patients -- usually two or three months after starting the drug treatments. Researchers suspect that interferon may deplete levels of the mood-related brain chemical serotonin. Studies suggest that patients who experience serious depression during treatment may be less likely to clear the virus from their system.

Be sure to call your doctor immediately if you develop signs of depression or feel suicidal during treatment; become unusually irritable, anxious or aggressive; or experience other unusual mood or behavior changes.

Fortunately, depression triggered by hepatitis C drugs can be treated. Researchers at the Northwest Hepatitis C Resource Center of the Portland VA Medical Center in Portland, Oregon, who conducted the depression study, gave the affected patients the commonly used antidepressant citalopram (Celexa). Within five to six weeks, 11 out of 13 patients were no longer depressed. The drug, like other selective serotonin reuptake inhibitors (SSRIs), helps make more serotonin available to brain cells. A Canadian report in September 2009 summarized nine trials and also concluded that evidence suggests SSRIs are safe and effective in treating depression during HCV treatment.

Many of the other moderate side effects associated with HCV treatment can also be eased or eliminated. For example, acetaminophen can relieve the muscle aches, headaches, and low-grade fever that sometimes accompany treatment. The dosage of ribavirin can be reduced if the asthma-like symptoms become severe. Even when side effects can't be eliminated, they usually go away within a few weeks after treatment is completed.

More serious side effects

Less commonly, ribavirin, peginterferon, and the combination of the two drugs can cause more serious complications. In most patients, ribavirin causes a small percentage of red blood cells to die. The severity of this side effect varies widely among patients. In most people, the loss of red blood cells can cause anemia. Symptoms of anemia can include fatigue, shortness of breath, irregular heartbeat, and headaches. Doctors closely monitor red blood cell counts, or hemoglobin, during treatment. In rare cases, the drop in red blood cells can cause chest pain, heart attacks, or strokes. (That's why ribavirin is not prescribed to people with serious heart or cerebral vascular disease.)

Other uncommon side effects of peginterferon and combination therapy include:

In rare cases, therapy for hepatitis C has been associated with heart failure, kidney failure, and vision loss, among other complications. It's important to remember that these side effects occur very rarely. For most people with hepatitis C, the benefits of treatment outweigh the risks.

In addition, many of the unwanted side effects of combination therapy can be relieved. Doctors can prescribe red blood cell growth factors to treat anemia, for instance. Acetaminophen helps ease the muscle aches and reduce low-grade fever. Doctors can also adjust the dose of both peginterferon and ribavirin to lessen side effects.

When should I contact my doctor about side effects?

Stop using interferon and ribavirin and call your doctor immediately or seek emergency medical help if you have:

In addition, talk to your doctor if you notice thinning hair, a rash or itchiness, nausea, dizziness, nervousness, irritability, insomnia, or pain or redness at the injection site.

What should I discuss with my doctor before using peginterferon and ribavirin?

Before taking this combination therapy, tell your doctor if you have had blood problems such as anemia, high blood pressure, heart problems; a history of depression or another mental illness; drug abuse; lung or breathing problems; kidney disorders; diabetes; thyroid problems; autoimmune disorders; psoriasis; eye problems; pancreatitis; an active infection, liver disease (other than hepatitis C); or bone marrow suppression, which is marked by low red or white blood cells or platelets.

These conditions mean that you might not be a candidate for combination therapy, or that your dosage might need to be adjusted.

Who should be treated -- and when?

Surprisingly, this is one of the most difficult and controversial questions in hepatitis C care. Most diseases are treated immediately after they are diagnosed. But because hepatitis C can infect people for years without causing any symptoms, let alone liver damage -- and because the treatments pose risks of their own -- many experts say it makes sense for some patients to wait.

At the same time, it's true that some patients do develop serious liver damage. For them, treatment can be life-saving. Unfortunately, it's not easy for doctors to determine who is at highest risk. Even a high level of the virus in the bloodstream isn't an indication of the seriousness of the infection.

In 2002, hepatitis C experts met to establish guidelines for treatment. The group, called the National Institutes of Health Consensus Development Conference Panel, recommended that treatment be limited to patients with elevated aminotransferase levels and evidence of progressive liver disease. The determining test is a liver biopsy, which removes a very small piece of liver tissue which can be obtained with a relatively non-invasive procedure called a needle aspiration. If the results show significant fibrosis (fibrous strands in the liver) or moderate to severe inflammation and dying liver cells, treatment is recommended.

As doctors learn more about hepatitis C, they gain additional useful insights into optimal treatment regimens. A study published in 2003 in the Journal of the American Medical Association showed that early treatment may make more sense for men than for women. Scientists found that the probability an infected man will develop cirrhosis over a 30-year period is between 13 and 46 percent. The same risk for a woman is only between 1 and 29. Also, the older people are at the time they become infected, researchers found, the more likely they are to develop serious liver problems.

In another recent advance, researchers at Baylor University Medical Center in Dallas, Texas, reported that it may be possible to predict how well the treatment will work even before the course of therapy is completed. In a study reported in the journal Hepatology, experts found that patients most likely to have a complete response were those who saw a significant drop in viral activity during the first 12 weeks of treatment. Patients who experienced little or no change in virus activity during that same period of time were unlikely to have a complete response, even if the treatment was continued for up to nine months.

In August 2009, scientists at Duke University Medical Center reported that they had identified the first genetic marker that predicts who is most likely to respond to hepatitis C treatment. This discovery provides valuable information for patients and doctors making decisions about the course of treatment.

Who shouldn't be treated?

Many people infected with hepatitis C virus aren't sick enough to justify treatment, while those with advanced liver disease are too sick to benefit from interferon/ribavirin, but may be eligible for liver transplant. For patients with certain other medical conditions, the risks of treatment may outweigh the benefits in some instances. Doctors often decide whether treatment is appropriate on a patient-by-patient basis. As a guide, the National Institutes of Health Consensus Development Conference Panel determined that treatment was NOT advisable for:

Ribavirin can cause severe birth defects, so women who are unable to stick to a birth control regimen should not take the drug. And because alcohol consumption interferes with peginterferon treatment and worsens the prognosis for people with hepatitis C, patients with a drinking problem should not be treated until they have stopped drinking, usually for a period of six months.

A new push to expand treatment

Guidelines for treatment are likely to change as researchers assess new findings. One controversy is whether patients with normal aminotransferase levels should be treated. The official guidelines say no. But approximately 30 percent of patients with chronic hepatitis C have normal aminotransferase levels. In general, normal or only moderately elevated aminotransferase levels indicate that the disease is progressing very slowly.

Yet a small percentage of patients with normal levels do develop advanced fibrosis or cirrhosis. Such patients are likely to benefit from treatment. Some experts argue that combination therapies are proving to be so successful that they should be offered to more patients.

Official guidelines are just that, of course. Doctors ultimately decide, in consultation with their patients, the best course of treatment. The decision is based on many factors, including the patient's age, test results, symptoms, and wishes.

The importance of staying informed

Only two decades since hepatitis C virus was identified, doctors have made giant strides in treating the infection. The prognosis for people with the disease has improved dramatically. It's likely to get even better as doctors learn to increase the benefits of existing drugs, and as new medications come along. Even now, new drug protocols and new drugs are being tested. The standard of care is likely to change as researchers refine their knowledge, so staying informed is a crucial part of staying healthy.

Everyone with hepatitis C, even if mild and nonprogressive, should make sure to see their doctor at least once or twice a year to get blood tests and to learn if there are any new developments in this rapidly changing field.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Chronic Hepatitis C: Current Disease Management. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). November 2006.

Seeff et al. The National Institutes of Health Consensus Development Conference management of hepatitis C 2002, Clinical Liver Disease, Feb 2003, pp 261-87

Foy, E. et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease, Science 2003 300: 1145-1148

Raison CL, et al. Depressive Symptoms and Viral Clearance in Patients Receiving Interferon-alpha and Ribavirin for Hepatitis C. Brain, Behavior, and Immunity. January 2005; 19(1): 23 - 27.

McHutchison, JG et al. Telaprevir with peginterferon and ribavirin for chronic HCV Genotype 1 infection. New England Journal of Medicine. April 2009.

New Biomarker Predicts Response to Hepatitis C Treatment. http://www.dukehealth.org/health_library/news/new_biomarker_predicts_res...

Sockalingam S and Abbey SE. Managing depression during hepatitis C treatment. Canadian Journal of Psychiatry. September 2009; 54(9): 614-25.


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco, and Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. Potter is board-certified in family practice.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HEPATITIS C AND CLINICAL TRIALS

Topics:

Existing drugs can eliminate hepatitis C in some patients, but they don't work for everyone. For that reason, a variety of clinical trials are under way to test new and as-yet unapproved treatments for HCV infection.

What are clinical trials?

Clinical trials are the means by which new drugs and treatments are tested to determine if they work. They are the engine that drives progress in medicine. For patients who have run out of other options, clinical trials offer a last chance at a potentially effective therapy. In some cases they provide access to research treatments before they are made widely available.

But it's important to remember that clinical trials often involve unproven therapies. There is no guarantee that the treatments under investigation will work. And there is always a chance that they may cause serious side effects. Still, by participating in clinical trials, patients help advance the science of medicine.

Are there guidelines to participate in a clinical trial?

Yes. If you or someone you know is interested in participating in a clinical trial, there are some important things to remember.

Clinical trials have specific guidelines about participation. To make sure clinical trials are safe and provide reliable scientific information, researchers carefully choose who can -- and who can't -- take part. Clinical trials include "inclusion criteria" (the requirements for participating) and "exclusion criteria" (factors that disallow people from taking part). These are usually spelled out in descriptions of clinical trials made available to the public.

Participants must be informed and give their consent. Doctors and nurses are required to explain the details of the investigation to prospective participants. They also provide an "informed consent" document, with the details of the study explained in writing. Participants are asked to sign the document. Additional information is sometimes provided during the study, as it becomes available.

Participants are always free to withdraw from a study. Even after you sign an informed consent document and join a clinical trial, you can withdraw at any time. Withdrawing can jeopardize research, however. So it's important to learn everything you can before agreeing to join a trial.

Not everyone in a study always receives the active drug or treatment. Some studies test an active drug against a placebo. In blinded studies, neither participants nor researchers are allowed to know who is getting the real drug and who is being given the placebo. (A sealed code is used to keep track for later analysis.) Blinded studies are essential to eliminate bias in interpreting the results. Typically, if a drug appears to be working effectively, researchers will decide to "unblind" the study and offer the new treatment to everyone in the study.

How are clinical trials conducte?

Clinical studies are conducted in four phases. Phase I trials test a new drug or treatment in a small group of people to make sure it's safe, to determine a safe dosage range, and to look at side effects. Phase II trials usually include more people and study both whether the drug is safe and whether it's effective. Phase III trials include even more participants. They are designed to confirm a treatment?s effectiveness, monitor its side effects, and sometimes compare it to commonly used treatments. In Phase IV trials, drugs that have already been approved are studied for more information about their benefits, uses, or potential risks.

Investigational drugs are sometimes offered outside of clinical trials. The FDA allows manufacturers of investigational drugs to offer them to people who might benefit but who don?t qualify for clinical trials. "Expanded access," as it's called, is usually offered to people with a serious or life-threatening illness. The drug must already have been shown to be safe and effective in well-controlled studies.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

Further Resources

For more information about clinical trials: National Institutes of Health http://www.ClinicalTrials.gov This site provides detailed information about clinical trials and has a search feature that locates on-going clinical trials.

CenterWatch http://www.CenterWatch.com This site includes a listing of clinical trials organized by state.

References

National Institutes of Health, An Introduction to Clinical Trials: http://www.clinicaltrials.gov

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated September 28, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HEPATITIS C AND LIVER TRANSPLANTS

Topics:

Most people know him as the bad guy JR Ewing on the TV show "Dallas." But lately the actor who played the part, Larry Hagman, has adopted a different role: champion for the cause of organ transplants.

In 1995, Hagman, who had advanced cirrhosis, received a life-saving liver transplant. Since then he has gone on to become honorary chairman of the U.S. Transplant Games, an Olympics-style competition held for patients who have received donated organs. Hagman called the games "a true celebration of a second chance at life for transplant recipients from across the country."

For patients with advanced hepatitis C liver disease, liver transplants can offer just such a second chance. Cirrhosis of the liver caused by HCV infection is the leading reason for liver transplants. The surgery is complicated and can be risky. Yet it saves lives. About 73 to 77 percent of adult patients survive the operation and resume normal lives. Some 90 percent of liver transplants in children are successful. And new advances in the surgery, including the use of combination anti-viral therapy and "live donor" liver transplants, are improving those odds.

Among those who beat the odds is David Crosby, formerly of the band Crosby, Stills, Nash, and Young. Learning from doctors at Johns Hopkins in the 1990s that chronic hepatitis C had "munched" his liver "to a truly amazing degree… so that I had very little function left," he received a long-awaited liver transplant in 1994. Today, the grateful musician says he is "having a ball" raising a 3-year-old, touring with one of his sons, and making a documentary about musician activism. In his spare time, Crosby has also found time to narrate public service announcements about hepatitis C. "A lot of people think that if they ignore the disease, it will go away," he told an interviewer recently. "It won't. It will come knock on your door."

Who qualifies for transplant

Because donated organs are in short supply, doctors carefully screen patients before putting them on the list to receive a liver.

In general, transplants are offered to patients who can't be treated using drugs or other therapies, and whose disease has become life-threatening. For HCV-infected patients, the most common reason for a transplant is severe cirrhosis, or scarring of the liver. Performing transplants on patients with liver cancer is less common and can be controversial. By the time cancer is detected, it has often spread too far to be cured by a liver transplant.

Transplants are usually not offered to people with ongoing drug or alcohol abuse problems, since the likelihood of success would be small. Crosby, for example, had experimented with needle drugs a few times and developed a serious drinking problem during his years on the road, but had been sober for 10 years before he learned he had hepatitis C. "I had already made the changes that I would recommend to anybody who discovers that they've got it, which are: Don't drink and don't use," he told Hep-C Alert. "I had decided that long before, or they wouldn't have done the treatment."

Timing is critical for patients who may need a liver transplant. Although transplantation is a last resort, it is important not to wait too long. If a patient's condition has seriously deteriorated, the chances of a successful liver transplant are lessened. Typically, a team from the liver transplant center determines, in consultation with the patient and family, whether a liver transplant is appropriate. Most centers have medical review boards that assess a patient's health information and make the final decision.

If a patient is approved, he or she is placed on the national waiting list for liver transplants. The wait can be a long one. It often takes more than a year to find a suitable donor.

Weighing the risks

Like all major surgeries, liver transplants carry risks of infection and bleeding. During the surgery, doctors sometimes have difficulty removing the diseased liver. Problems can also arise if the blood vessels connected to the new liver develop clots, reducing blood supply to the transplanted organ. Once the surgery is completed, there is risk that the immune system will reject the organ. This danger can usually be minimized with drugs that suppress the rejection mechanism.

The chances of surviving a liver transplant vary depending on the age and condition of a patient. On average, about three out of four transplant patients survive the first five years after transplantation. Those might not seem like very good odds. But among patients who are in good condition, the survival rate is as high as 90 percent. Among critically ill patients, the survival rate is about 50 percent.

Surgery and recovery

Liver transplants are performed only at major medical centers around the country, by expert teams of transplantation surgeons. In the past, donated organs came only from people who had died and agreed to donate their organs. Recently some centers have also begun performing "live donor" organ transplants, in which part of the liver from a matched donor is removed and transplanted. The surgery is possible because healthy livers can regenerate themselves. Within a year, the part of the liver removed from a donor has fully grown back.

Transplant patients typically spend a few days in an intensive care unit after surgery, where their condition can be carefully monitored. Then they are moved to a regular hospital room for a stay of two to three weeks, on average. Patients who are critically ill at the time of the transplant may need to remain in intensive care and in the hospital longer, up to three months. Once patients leave intensive care, they begin to resume normal diets and are encouraged to get out of bed and walk.

The paradox of rejection

The most dangerous risk for transplantation patients is rejection. This occurs when the body's immune system attacks and destroys the transplanted organ.

Why does the immune system, which is there to protect us, try to reject the life-saving transplant? Rejection occurs because the immune system's job is to target and destroy foreign cells that pose a risk. Immune cells identify foreign cells by looking at unique molecular fingerprints on their surfaces and comparing them to the body's own unique molecular fingerprints. In this way, the immune system distinguishes between "self" and "non-self." A donor organ comes from someone whose cells have a different molecular fingerprint. Unfortunately, the immune system reacts as if the body has been invaded. It unleashes its destructive power to get rid of the foreign cells that it has mistakenly perceived as a threat. If not suppressed, the immune system can destroy a transplanted liver within days.

Several drugs have been developed that stop or slow the rejection process. Anti-rejection drugs may be given by injection during the first several weeks and later in pill form.

All anti-rejection drugs work by suppressing the immune system. As a result, they make patients more susceptible to infections. Other side effects include elevated blood pressure, fluid retention, puffiness, and bone loss. Over time, as the body begins to tolerate the new organ, patients require less anti-rejection medicine. Still, it's likely that all transplant patients will have to take the drugs for the rest of their lives. Because of the potentially serious side effects, doctors typically try to lower the dosage to the smallest amount required to prevent rejection. To prevent serious infections, transplant patients are often given antibiotics in pill form.

Liver transplantation doesn't always succeed. In some cases, the transplanted organ may fail to function. Clots forming in the blood vessels that supply the transplanted organ may cut off blood supply, starving the new liver. Sometimes doctors are unable to stop the rejection process. If the liver begins to fail, a second transplant may be necessary.

For most patients, however, liver transplants are nothing short of a miracle. People who were seriously ill, like Crosby, have been able to return to full, active lives. Some, like snowboarder Chris Klug, compete in the US Transplant Games as a way to inspire other patients facing transplants. In July 2000, Klug received a liver transplant because of a rare congenital liver condition. Five months after the surgery he won a World Cup in the parallel giant slalom. He took home a bronze medal in the 2002 Winter Olympics.

New advances ahead

For HCV-positive patients, a liver transplant doesn't offer a cure. Because HCV is circulating in the bloodstream, the transplanted liver inevitably becomes infected with the virus. Over time, the infection can begin to injure the new liver.

Fortunately, advances in treating hepatitis C promise to slow that process dramatically. The higher the viral load at the time of surgery, studies have shown, the more quickly symptoms of hepatitis C infection recur in transplant patients. That finding led scientists to wonder if anti-viral treatments given before surgery could lower viral levels and protect the new liver from damage. To find out, experts at Loyola University Medical Center in Illinois have begun aggressively treating HCV patients with high doses of alpha interferon. Early results suggest that the treatment may help delay recurrence of the disease.

The use of "live donor" liver transplants, meanwhile, could significantly increase the availability of donor organs. Because this technique poses some risk to the healthy donor, however, it remains controversial. In 2002, the National Institutes of Health launched a seven-year study to assess the technique and identify the safest ways to perform the procedure.

Another new advance could help buy time for patients awaiting donor livers. The Mayo Clinic laboratory is developing a bioartificial liver, which operates outside the body like hemodialysis but contains live, functioning liver cells. This new form of therapy is intended not only for patients prior to transplantation but also for those in need of chronic supportive therapy.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Thomas, R.M. et al., Infection with chronic hepatitis C virus and liver transplantation: a role for interferon therapy before transplantation, Liver Transplantation, September 2003, pg. 905-915

Wiesner, R.H. et al., Recent advances in liver transplantation, Mayo Clinic Proceedings, February 2003, pg. 197-210

The Texas Liver Coalition, www.texasliver.org

HCV Advocate newsletter, An artificial liver device, July 2003

Hep-C Alert Interviews Crosby, www.hep-c.org

US Department of Health and Human Services. Chapter III: Pediatric Transplantation in the United States, 1996-2005. http://www.ustransplant.org/annual_reports/current/chapter_iii_AR_cd.htm

US Department of Health and Human Services. 2006 OPTN/SRTR Annual Report. http://www.ustransplant.org/annual_reports/current/chapter_i_AR_cd.htm

Mayo Clinic. Scott L. Nyberg (artificial liver and liver transplantation). http://mayoresearch.mayo.edu/mayo/research/nyberg_lab/

Mayo Clinic. Hepatitis C. September 2007. http://www.mayoclinic.com/health/hepatitis-c/DS00097


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated November 10, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

HEPATITIS C AND STRESS

Topics:

It's natural for everyone to feel stress, but people with hepatitis C have additional concerns. There's the prospect of medical tests and procedures, worry over medical bills, and the fear of infecting others to name a few. Some people feel angry either at themselves or at someone else -- or simply at the rotten blow that life has handed them. That anger can lead to depression, which only adds to the burden of emotional stress.

Being diagnosed with hepatitis C can be especially stressful because of the uncertainty associated with its course. Uncertainty creates a feeling of helplessness, which, researchers have learned, is one of the key factors in stress. Having a lot of demands on you isn't inherently stressful, after all. Not having control over those demands is.

Taking stress seriously

Stress can erode the quality of life, taking the pleasure out of work and relationships. It can also compromise overall health. There is no direct evidence that chronic stress worsens hepatitis C infection or injures the liver, but there is good evidence that chronic stress can impair the immune system. Easing stress, on the other hand, can boost immunity.

The most startling evidence comes from experiments involving AIDS patients. In research conducted by Michael Antoni, PhD, a psychologist at the University of Florida at Coral Gables, volunteers who took part in group sessions on stress reduction lowered their levels of cortisol and noradrenaline -- two hormones associated with stress that are known to impair immunity. One year after learning and practicing stress-reduction techniques, the volunteers had significantly more new T cells, the immune cells that are generated to fight infections. So by learning to handle stress, the volunteers were actually able to restore some of their immune function.

Reducing stress has also been shown to alleviate symptoms of other conditions, such as heart disease and asthma. Learning to cope with stress is obviously important for your emotional well-being, but it's also important for your overall physical health.

Know the danger signs

The first step is recognizing the symptoms of too much stress. Remember: Not all stress is negative. Pressures at work and occasional tensions within your family are a normal part of life. Sometimes stress pushes you to do your best. However, stress becomes negative when you feel as if you can't escape it, or when you feel as if the pressures in your life are out of control.

The immediate physical reaction to stress can include high blood pressure, perspiration, a racing pulse, and a fluttering feeling in your chest. Adrenaline, the biochemical that readies the body for fight or flight, surges into the bloodstream. Other typical signs of stress include:

Unfortunately, there is no objective test for stress. But if you feel as if the pressures of dealing with hepatitis C are a problem for you, it's time to make some changes.

Different ways of reducing stress work for different people. Most people try a few approaches before finding the ones that work best for them. The good news is that you won't have to turn your life upside down to tame stress, says psychologist Frederic Luskin, PhD, a researcher at the Stanford University Center for Research in Disease Prevention. "A few simple techniques, things you can do anywhere and that don't have to take more than a few minutes, can stop the stress response before it goes out of control."

Here are seven strategies for beating stress:

Clear your head

At least once every day, find a quiet corner and take five or 10 minutes to sit quietly and do nothing. Sitting quietly slows heart rate and reduces blood pressure, countering two of the most obvious effects of stress. A quiet break can also increase your sense of control over events. At the Center for Mindfulness in Medicine, Health Care, and Society at the University of Massachusetts, patients are encouraged to sit and become aware of their feelings and the sounds around them. Taking a quiet break like this can help you get past the fatigue that is a common symptom of hepatitis C infection.

Refocus your thoughts

Shifting the focus of your thoughts from things that worry you to things that bring you happiness can change your mood for the better -- and ease stress. Psychologists call this technique "positive emotion refocusing." Thinking pleasant, calming thoughts can actually counteract the physiological changes that occur during stress by slowing your heart rate and lowering your blood pressure, for example.

Take a deep breath

Deep breathing exercises have been part of meditation techniques for centuries -- with good reason. Concentrating on the simple act of inhaling and exhaling almost inevitably calms mind and body. Some people get even more benefit from repeating a mantra-like word or phrase each time they breathe in. Another technique is to picture each inhaled breath filling your body with soothing light. Imagine each exhaled breath blowing away tension and stress.

Have a laugh

Laughter really is the best medicine, according to studies at Loma Linda University in Loma Linda, California. Researchers there have shown that laughter lowers levels of the stress hormones cortisol and epinephrine. A good belly-laugh also boosts immunity and these physiological effects can last up to 24 hours. Amazingly, the team at Loma Linda found that just looking forward to something funny helps. Telling volunteers that they would participate in an experiment that involved watching a humorous video lowered their stress levels and created a more positive mood.

Do what you love

Managing a health problem like hepatitis C isn't easy. The best solution is to make time in your day for at least one thing you really love to do, whether that's listening to music, dancing, gardening, playing with the kids or the dog, painting, or reading. Listening to music may be especially soothing. At Monash University in Victoria, Australia, two groups of students were told to prepare an oral presentation. One group worked in silence. The other listened to the gentle strains of Pachelbel's Canon in D Major. Blood pressure and heart rate were more likely to climb among the silent workers, while those who listened to music reported feeling much less stress. Another study, this one at the Medical College of Ohio in Toledo, found that patients who listened to music while undergoing uncomfortable medical procedures required less sedation.

Take a hike

Exercise of any sort can help ease stress. Walking is an especially good choice because you can do it almost anywhere. Even if you're feeling tired as a result of your condition, you probably have the energy for at least a leisurely walk around the block. And walking has proven benefits. In an investigation at Stanford University School of Medicine, researchers studied people who were taking care of relatives with Alzheimer's Disease. Volunteers who began walking for 30 to 40 minutes four times a week reported feeling less distressed and sleeping better. Also, tests showed that their blood pressure was more likely to hold steady when they were under pressure.

Change what you can

If you notice yourself getting stressed out again and again in the same situations or because of the same problem, think about what you can change. Overwhelmed by chores at home? Create a chore-sharing plan with the other members of your household. Does your blood pressure climb every time you find yourself searching for your glasses or the car keys? Decide on a place to put them and get into the habit of placing them there. Having trouble with your boss at work? Consider sitting down to talk about the situation and offer constructive ways to make things better.

Accept the rest

Of course some of life's frustrations and worries can't be eliminated. If you or someone close to you has been diagnosed with hepatitis C, this is a reality you have to live with. It's important to recognize what you can't change and move on. The process is very much like forgiving someone who has hurt you, according to psychologist Luskin. Accepting what you can't change allows you to let go of hurt and anger and focus on more constructive thoughts.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Benson, H. The Relaxation Response. Harper Collins

King, AC. et al. Effects of moderate-intensity exercise on psychological, behavioral, and emotional responses to family caregiving: a randomized controlled trial, Journal of Gerontology, Jan 2002, pp M26-36

Smolen, D. et al. The effect of self-selected music during colonsocopy on anxiety, heart rate, and blood pressure, Applied Nursing Research, Aug 2002, pp 126-36

Knight, WE et al. Relaxing music prevents stress-induced increases in subjective anxiety, systolic blood pressure, and heart rate in healthy males and females, Journal of Music Therapy, Winter 2001, pp 254-72

Berk, LS. et al. Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter, Alternative Therapies in Health and Medicine, Mar 2001, pp 62-76

Berk, et al. Neuroendocrine and stress hormone changes during mirthful laughter, American Journal of Medical Science, Dec 1989, pp 390-396

Antoni, MH. Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection, Stress, Sep 2003, pp 173-88

Antoni, et al. Cognitive-behavioral stress management reduces distress and 24-hour urinary free cortisol output among symptomatic HIV-infected gay men, Annals of Behavioral Medicine, Winter 2000, pp 29-37


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated October 29, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

ALCOHOL AND HEPATITIS C

Topics:

If you've been diagnosed with hepatitis C, your doctor has probably advised you to give up alcoholic beverages. For some people, this can be one of the most difficult lifestyle adjustments to make. But it's also one of the most important.

Several studies have shown that among people with hepatitis C, regular drinkers have higher levels of virus than nondrinkers, according to Wen-Zhe Ho, MD, director of retroviral research at the Children?s Hospital of Philadelphia. Studies also show that when people infected with the hepatitis C virus (HCV) stop drinking alcohol, levels of the virus decrease.

Researchers have found that alcohol causes the hepatitis C virus to multiply in the liver by increasing the activity of a protein that triggers the virus to make new copies of itself. These new copies speed the progress of the infection and raise the risk of liver damage.

Protecting your liver

There are other compelling reasons not to drink alcoholic beverages if you have hepatitis: One of the liver's jobs is to process alcohol. Too much alcohol can poison liver cells and cause a form of the disease called alcoholic hepatitis. If people continue to drink excessively, the condition can lead to permanent liver damage, or cirrhosis.

As you would expect, alcoholic hepatitis is frequently diagnosed in alcoholics. But it can also show up in some social drinkers because the liver's ability to process alcohol varies widely from person to person. Women, for instance, metabolize alcohol more slowly, so they seem to be at greater risk of suffering liver damage from drinking alcohol than men are.

If you've been diagnosed with hepatitis C, drinking alcohol adds to the strain on the liver, increasing the risk of damage to cells. That raises the danger of cirrhosis and liver cancer. If your liver has already been damaged by the virus, drinking can make things even worse.

For people being treated with interferon-alpha, there's another strong reason not to drink: The same scientists who showed that alcohol spurs the growth of the hepatitis C virus also found that alcohol weakens the effect of interferon-alpha. Drinking any amount of alcohol can interfere with treatment.

How to get help

The risks from alcohol are so serious that doctors usually advise people with drinking problems to abstain from alcohol for six months before beginning treatment.

Some people find it easy to stop drinking alcohol. But others, especially alcoholics, find it very difficult. One out of every 12 Americans – 17.6 million in all -- suffers from alcoholism or alcohol abuse, according to the National Institute on Alcohol Abuse and Alcoholism. For some people, a diagnosis of hepatitis C is the wake-up call that motivates them to make healthy lifestyle changes. But the added stress of having a potentially serious illness like hepatitis C can also make it harder for others to take control of their lives and stop drinking.

Taking the step

The toughest step can be admitting that there is a problem. If you or a loved one has been diagnosed with hepatitis C and are struggling with a doctor?s advice not to drink, ask for help. There are many resources available to help people overcome a drinking problem. Talk to your doctor or call the National Drug and Alcohol Treatment Referral Routing Service at (800)662-HELP for information about treatment programs in your community. Acknowledging that drinking is a problem could be the most important step toward staying healthy.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Lauer, GL. et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

Ho, W. et al. Alcohol increases hepatitis C virus in human cells, Hepatology, July 2003, pp 57-65

Vento, S. et al. Does hepatitis C virus cause severe liver disease only in people who drink alcohol? Lancet Infectious Diseases, 2002, pp 303-309.

Pessione, F. et al. Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking, and abstinence, Liver International, Feb 2003, pp 45-53.

The American Liver Foundation, Myths vs. facts about alcohol and the liver, http://www.liverfoundation.org

National Institute on Alcohol Abuse and Alcoholism. FAQs for the General Public. February 2007. http://www.niaaa.nih.gov/FAQs/General-English/default.htm


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive

DRUGS & CONDITIONS

NEW ADVANCES IN HEPATITIS C RESEARCH

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It has been only 20 years since the hepatitis C virus was first identified. In that time, an extraordinary amount of progress has been made in the fight against this virus. Still, much needs to be done. Improved diagnostic tests are needed to identify people infected with HCV more precisely and less expensively than is possible today.

Better ways to prevent transmission are urgently needed. With an astonishing 3 percent of the world's population infected with HCV, the most intense research is being done in the area of treatment. Current treatments eliminate the virus in only a little more than half of all patients. The drugs also have unwanted side effects that make it difficult or impossible for some patients to take them. In all these areas, rapid progress is being made. Here's an overview from several fronts in the battle against HCV:

New and more effective treatments

Intense research efforts around the world are focused on developing new and more effective treatments to eliminate or control the hepatitis C virus. Scientists are improving existing drugs in significant ways. The development of pegylated interferon, or peginterferon, has significantly increased interferon's effectiveness. By combining peginterferon with ribavirin, doctors are achieving even better results. A new version of ribavirin called viramidine (taribavirin) is under investigation and at least one study has shown that it triggers fewer side effects, including anemia, than the original ribavirin. It has not yet been approved by the FDA, but has shown promise in clinical trials.

Recent research on a hepatitis C-specific protease inhibitor called telaprevir also forecasts a new era in treatment. In April 2009, the New England Journal of Medicine reported on a study that showed significant improvement in the chances of being cured when telaprevir was added to the current standard therapy, and treatment took only half the time. If further studies confirm these results, telaprevir could soon be approved by the FDA.

Another drug that shows promise in clinical trials is the anti-cholesterol medication fluvastatin. A small study of veterans in 2008 found that fluvastatin may help to temporarily reduce hepatitis C levels. Now researchers will look at combining it with standard therapy in an effort to improve cure rates.

Meanwhile, entirely new drugs are also being developed to fight HCV. Researchers hope to use the same model that has proved so successful in developing HIV/AIDS therapies -- targeting enzymes that the virus needs to reproduce. The specific drugs that fight HIV don't work against HCV, because the two viruses use different kinds of enzymes, but the same strategies are likely to work in conquering them.

The three most likely targets include three different classes of enzymes: proteases, helicases, and polymerases. Advances are being made against all three. For example, in 2003, researchers announced the identification of a protease enzyme that HCV uses to evade the immune system. The enzyme, labeled NS3/4A, inhibits a key immune system molecule that regulates interferon. The scientists used a protease inhibitor that prevented the virus from making NS3/4A. The experimental drug restored the immune system's ability to respond to the virus.

"Now that we know NS3/4 inhibition essentially restores the host's immune response to the virus, we can assess hepatitis drug candidates for this ability as well," says Michael Gale Jr., PhD, of the University of Texas Southwestern Medical Center at Dallas, on behalf of the National Institute for Allergy and Infectious Diseases. In 2008, experts reported encouraging findings from a clinical trial that showed that the use of the polymerase inhibitor R162 in combination with standard therapy can significantly improve treatment results. Extensive testing remains to be done before these and other new antiviral drugs are approved. Still, the fact that so many are in the pipeline is encouraging, experts say. As new drugs become available, doctors will be able to create "cocktails" of treatments, much as they do for HIV-infected patients today. By individualizing therapy, doctors will be able to treat patients more effectively and with fewer side effects.

In the meantime, another discovery is providing valuable information for patients and doctors making decisions about the course of treatment. In August 2009, scientists at Duke University Medical Center reported that they had identified the first genetic marker that predicts who is most likely to respond to HCV treatment.

New ways to study hepatitis C

Although HCV grows quickly in the human liver, researchers have struggled to find ways to grow the virus in the laboratory. Recently, scientists developed strains of mice that can be infected with HCV, an advance that should help speed progress in understanding the virus and developing treatments. And in 2008, scientists at the University of California, San Diego announced that they had succeeded in developing the first tissue culture of normal human liver cells that can be infected with the virus in the laboratory. This should facilitate more rapid testing of new drug candidates in the future.

More accurate diagnostic tests

Although existing tests to detect and measure HCV are highly sensitive and specific, they are not perfect. In some cases the tests fail to detect infections (false negatives). In other cases they show positive readings in people not infected, or in people whose bodies have actually eliminated the virus (false positives). Tests that measure the amount of virus in the blood, or viral load, vary widely in quality. Researchers are working on developing more reliable tests that would reduce false negatives and false positives. Another goal is to develop less expensive tests, for use in poorer countries, where cost can make testing prohibitive.

A vaccine against hepatitis C

The transmission of HCV through blood transfusions and organ transplants has been largely stopped, thanks to increasingly sophisticated screening tests. Now more must be done to prevent its spread among drug users. Needle exchange programs and counseling on safe methods to handle syringes could help. Ultimately, the gold standard for disease prevention is a vaccine. Vaccines "prime" the immune system to detect and destroy invading germs before they can gain a foothold. Some vaccines can even be used to treat people already infected with a virus by boosting their immune response. Unfortunately, experts are still far from developing a hepatitis C vaccine. The biggest challenge is the fact that hepatitis C virus is constantly changing its shape to elude immune detection. For this reason a vaccine that protects against one form of the virus may not protect against others. Still, the scientific community is making progress in identifying stable regions of the virus that do not change, and is exploring a variety of new approaches for developing vaccines.

Staying informed in a fast-changing field

The swift progress being made on many fronts offers encouragement to everyone infected with HCV. But rapid developments in medicine can also cause confusion and frustration. Preliminary results often make headlines years before new drugs are available. Popular articles may highlight positive results from studies and then fail to follow up when subsequent tests show problems with a new drug or treatment. Sorting through all the information in a fast-changing field like HCV research can be daunting. Two strategies can help you stay abreast of new developments without becoming overwhelmed.

First, find a few reliable sources of information and stick with them. Web sites sponsored by federal health agencies like the National Institutes of Health are a good place to start, as they are frequently updated and experts carefully screen the information posted.

Here are a few recommended sites:

The National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/topics/hepatitis/hepatitisc

National Institute of Diabetes and Digestive and Kidney Diseases http://www.digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm

National Center for Complementary and Alternative Medicine http://www.nccam.nih.gov/health/hepatitisc/

Second, talk to your doctor. Most doctors want patients to be informed and to ask questions. What's more, your doctor can help you evaluate new findings and put them in the context of other research on hepatitis C.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

Pietschmann, T. Tissue culture and animal models for hepatitis C. Clinical Liver Disease, Feb 2003, pp 23-43

Frick, D.N. Helicases as antiviral drug targets. Drug News Perspectives, July-Aug 2003, pp 355-62

Foy, E. et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science, Apr 17, 2003

Lechmann, M. et al. Vaccine development for hepatitis C. Liver Diseases Section, NIDDK, National Institutes of Health, Seminars in Liver Disease, Medscape

Watson, J. Prospects for hepatitis C virus therapeutics: levovirin and viramidine as improved derivatives of ribavirin. Curr Opin Investig Drugs, May 2002, pp 680-3

HCV Advocate. HCV Reports from the Retrovirus Conference, Apr 2003

HCV Advocate. Bayer Receives Viral Load Test Approval, May 2003

The National Institute for Allergy and Infectious Diseases.

McHutchison JG, Manns MP, Longo DL. Definition and management of anemia in patients infected with hepatitis c virus. Liver International. May 2006; 26(4): 389-98.

D Nelson, PJ Pockros, E Godofsky, et al. High End-of-Treatment Response (84%) After 4 Weeks of R1626, Peginterferon Alfa-2a (40kd) and Ribavirin Followed By a Further 44 Weeks of Peginterferon Alfa-2a and Ribavirin. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.

Pockros P, et al. R1626 plus peginterferon alfa-2a provides potent suppression of HCV RNA and significant antiviral synergy in combination with ribavirin. Hepatology. August 2008.

Bader T et al. Fluvastatin inhibits hepatitis C replication in humans. American Journal of Gastroenterology. June 2008; 103(6): 1390-92.

Buck M. Direct infection and replication of naturally occurring hepatitis C virus genotypes 1, 2, 3, and 4 in normal human hepatocyte cultures. PLoS One. July 16, 2008; 3(7).

Marcellin, P et al. Safety and efficacy of viramidine versus ribavirin in VISER2: Randomized, double-blind study in therapy-naïve hepatitis C patients. Journal of Hepatology. October 2009.

McHutchison, JG et al. Telaprevir with peginterferon and ribavirin for chronic HCV Genotype 1 infection. New England Journal of Medicine. April 2009.

New Biomarker Predicts Response to Hepatitis C Treatment. http://www.dukehealth.org/HealthLibrary/News/new_biomarker_predicts_resp... http://www.niaid.nih.gov/dmid/hepatitis/

National Institute of Diabetes and Digestive and Kidney Diseases http://www.digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm

National Center for Complementary and Alternative Medicine http://www.nccam.nih.gov/health/hepatitisc/


Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.

Last updated December 18, 2009

Copyright © 2003 Consumer Health Interactive