Benh viem gan

Hepatitis C: A silent killer
There is no vaccine. No truly effective treatment. And the death toll is rising


BY NANCY SHUTE


Janet Gobeille Crenshaw didn't suspect a thing when, eight years ago, she got a letter from the Red Cross after donating blood.

"Please don't come back," she recalls the letter saying. "See your doctor. You've tested positive for hepatitis C." "I thought, 'Well, what's that?' "

Her doctor told her not to worry about it, and she didn't. It wasn't until last summer that Crenshaw, a computer systems analyst for IBM in Dallas, decided she'd better find out something about the disease that had led to the rejection of her blood. She didn't like what she found.

Hepatitis C is a killer. About 10,000 people die of the disease each year, and the death toll is rising. It has infected four times as many people as has HIV, the virus that causes AIDS. At least 4 million Americans have it--2 percent of the population. "Hepatitis C is a grave threat to our society," Surgeon General David Satcher warned a congressional subcommittee this spring. "Many Americans infected with hepatitis C are unaware they have the disease."

What makes hepatitis C even more frightening is that while the public and the medical community have focused on AIDS, hepatitis C, a virus transmitted by exposure to contaminated blood, has lurked largely unknown. People seldom get sick when first infected with the virus, unlike what happens with its cousins hepatitis A and B. Instead, the microbe quietly damages the liver, an organ with many vital functions, for 20 years before symptoms emerge. People like Crenshaw, 49, who contracted the disease in 1981 through a blood transfusion, are only now becoming sick. "Hepatitis C is an insidious disease," says Willis C. Maddrey, a hepatitis specialist at the University of Texas Southwest Medical Center. "It creeps up on you."

Though the number of new hepatitis C infections is dropping, thanks to efforts that began in 1990 to screen the virus from the blood supply, the number of people falling ill is rising. Officials with the federal Centers for Disease Control and Prevention predict that in the next 10 years the hepatitis C death toll will triple, eclipsing that of AIDS. The costs--financial, social, and emotional--will be huge. Health care already costs more than $600 million a year, according to Satcher. And no one can calculate the value of someone like Janet Crenshaw to her family.

Her experience isn't unusual. She never would have known she was infected if she hadn't been a blood donor. Last year, when she finally connected with a doctor who knew something about the disease (many family doctors aren't up to speed on hep C), a liver biopsy revealed fibrosis, scarring caused by the virus. (Like Crenshaw, 60 percent of those now infected are in their 30s and 40s; many of them will become chronically ill in the prime of their lives.)

Crenshaw, married just two years with two teenage stepdaughters, read enough to know that the odds are 8 in 10 that she will develop chronic hepatitis with some inflammation of the liver, and 1 in 5 that she will develop cirrhosis, which kills liver cells and impairs the organ's ability to perform vital tasks such as filtering toxic substances from the blood. Liver cancer is a 1 to 5 percent risk; that risk increases by as much as 4 percent a year with cirrhosis. The treatment for cancer and cirrhosis is a liver transplant. But last year 10,000 names were on the list for transplants, and only 4,000 organs were available. "I married a widower," Crenshaw says. "The last thing I want is for him to go through that again."

Last fall, Crenshaw started on alpha interferon, a naturally occurring protein that is the primary treatment for hepatitis C. For four months she injected herself three nights a week after dinner. Her hair fell out; she felt achy and tired, as with an endless bout of the flu. Interferon is notorious for inducing flu-like symptoms and depression; 5 percent to 10 percent of patients are so miserable they quit the treatment. Crenshaw kept working, but she tucked a pillow and blanket in the car so that she could slip out of the office and nap.

And after all that, the interferon didn't work. Unfortunately, that's not unusual; interferon clears the virus from the bloodstream for only about 20 percent of patients. Two months ago, Crenshaw started treatment with Infergen, a bioengineered version of interferon that was approved by the FDA last October. Last week, she found out that she had no response to the Infergen, either. She's continuing treatment in the hope it will work over time. "The last thing I want to do is accidentally spread it to someone. I worry about passing it to my husband. In the back of my mind, it's always there."

The virus's origins remain mysterious, but it probably first spread widely during World War II. Blood transfusion, then a new technology, was common on the battlefield, and sterile equipment was rare. In the 1960s, researchers began noticing liver problems among people who had had transfusions. But it wasn't until the 1970s that scientists were able to differentiate a new strain. "We found there was a third kind of hepatitis, which we called non-A, non-B hepatitis," says Robert Purcell, an NIH researcher who led the effort to study the new virus. "We thought [its identity] would be resolved very quickly." That was in 1975. It wasn't until 1989 that a biotechnology firm replicated part of the virus and created the first blood test for it. Hepatitis C remains largely a mystery; it is one of the RNA viruses, which are less well understood than are DNA viruses, and it has defied efforts to grow it in a test tube. Like HIV, it mutates its protein coating to disguise itself from the body's immune defenses; there are at least six different genotypes of hepatitis C, and more than 30 subtypes. Unlike HIV, it doesn't attack the immune system, making victims less prone to secondary infections that plague AIDS patients. The HIV virus also progresses more quickly, and is more lethal.

AIDS preoccupation. But AIDS has played a role in the hepatitis C story. Critics of the government's response to hep C, including former Surgeon General C. Everett Koop and members of Congress, say public-health authorities let themselves get preoccupied with AIDS and failed to alert the public to this other threat. Others say it would have been irresponsible to inform people if there was no way to help them. "There isn't a lot we've been able to do," says Miriam Alter, chief of epidemiology for hepatitis at the CDC. Reliable tests weren't available until 1990; and, Alter adds, "therapy has been very disappointing for most people."

Now the federal government is making its first public moves against the disease. The Department of Health and Human Services is finalizing a rule requiring blood banks and hospitals to notify people who likely contracted hepatitis C through transfusions between January 1988 and June 1992. This is cumbersome; the institutions must first search their databases for blood donors who later tested positive for hepatitis C, then search again for patients who got blood from those donors, an estimated 300,000 people. Notices won't go out for at least six months.

But many more people got transfusions before 1992, and those people will not be individually notified. In any event, transfusions account for only 7 percent of hepatitis C infections. The government hopes to alert the millions of other probable hepatitis C carriers with a $4 million public-education campaign.

Junkies. Most Americans remain in the dark about hepatitis C and how it spreads. And the authorities don't know all risk factors, which adds to the confusion. The medical community has tra***ionally considered hepatitis C a "junkie's disease," because it's easily spread by sharing intravenous needles. Blood transfusions before 1990, kidney dialysis, clotting factors for hemophilia, and organ transplants also are known risk factors. People who received blood before 1970, when hospitals quit using commercially provided blood, face a greater risk of infection than do those transfused later. Paid blood donors were often Skid Row denizens with high rates of hepatitis and other infectious diseases.

The CDC says 10 percent of transmissions are unexplained, and more than 50 percent of cases are linked to intravenous drugs. David Crosby, 1960s rocker and heavy drug user, had a liver transplant in 1994 as a result of hep C. But many people who merely experimented with IV drugs may have become infected, too. "These are [now] solid citizens who just played around in the late '60s or early '70s," says Emmet Keeffe, a professor of medicine at Stanford University. Snorting cocaine, which many people thought safe, is also risky, it turns out. Microdroplets of blood dislodged when a coke straw bumps the delicate capillaries inside the nose can be passed on the end of the straw.

Richard Wallace wonders whether he's among those paying the price for the sins of youth. A 43-year-old St. Petersburg, Fla., businessman, he found out he has hep C after a blood test in 1991 for more life insurance following the birth of his second child. Wallace figures he got the disease from a surgical procedure he had as a child, or perhaps from trying cocaine as a young man. Since then he has married, had two children, built a successful bakery-supply business, even joined the Rotary Club. The business is gone now; he sold it when he realized the hepatitis was progressing quickly. He also sold his house, buying a smaller one that took less maintenance. He hasn't been able to work since October, and a new regime licensed this month, combining interferon with ribavirin, an antiviral, failed to lower his high viral load. He's now trying high daily doses of Infergen and plans to try whatever new treatments come along. "I've got to protect myself," Wallace says. "If I slip into cirrhosis, it's the no-return point."

The CDC recently attributed 20 percent of hepatitis C cases to ***ual transmission. Having multiple partners appears to be a risk, but the virus is not easily ***ually transmitted, unlike HIV. And the transmission rate among monogamous partners is quite low, around 3 percent. Another 10 percent of cases are from blood transfusions or exposure at work or home; surgeons, nurses and emergency workers are at risk from blood splashes and needle sticks. Country singer Naomi Judd says she got hepatitis C while working as a nurse before she became famous. Hepatitis C carriers are cautioned not to share razors or toothbrushes. "Everybody is at some risk for hepatitis C," says Andi Thomas, founder of Hep-C Alert, an activist group in Florida. "You're not safe just because you've lived a safe and sane life."

U.S. veterans appear to have higher rates of hepatitis C than the civilian population. In a recent six-week survey, 20 percent of patients at the Washington, D.C., VA Medical Center tested positive for hepatitis C; 10 percent tested positive at the San Francisco VA hospital, and half of the VA's liver-transplant patients have the disease. Dr. Thomas Holohan, chief of patient-care services, says that "veterans have a higher incidence of drug use than the civilian population," and that Vietnam veterans were more likely to have been exposed to blood during transfusions and evacuations. Last week, the Department of Veterans Affairs sent its doctors a directive to screen all their patients for any of 10 factors, including tattoos and "intemperate alcohol use," then test those with risk factors for virus antibodies. Within the next month, the VA also will issue formal treatment guidelines.

Testing, testing. Federal health officials say anyone with a major risk factor should get tested for hepatitis C. So should people who show elevated liver enzymes on a standard blood test (but those can also rise from having a glass of wine the night before). Some insurance companies won't pay for hep C tests, so the simplest and cheapest way to get tested, doctors say, is to donate blood. Donors are notified within six months if there is a problem, and tainted blood is destroyed. (For free information, contact the American Liver Foundation at 888-443-7872 or www.liverfoundation.org.)

People who find out they have hepatitis C face the question of whether or not to get treatment. It's not an easy decision. A 1997 report from the National Institutes of Health recommends that patients with elevated liver enzymes and fibrosis be treated with interferon but said it's unclear whether people with mild cases, or those with advanced disease, will benefit. Drinking alcohol can exacerbate the disease, and doctors recommend quitting, or cutting back to one drink a day.

Many drug companies, enticed by a global market of 170 million potential customers, are working on new hep C treatments. A vaccine is nowhere on the horizon because it's very hard to come up with enough variations to attack the virus's many forms. But some potential treatments look promising, particularly protease inhibitors similar to those that have proved so successful with AIDS. The drugs could disrupt the virus's enzymatic processes and block its replication. But clinical trials are at least several years off. Until we have better weapons to use against hepatitis C, we have to learn to live with it.

With E. F. Licking and Stacey Schultz

The ABCs of hepatitis

Hepatitis A and B, both viruses that affect the liver, were identified following World War II. Since the 1970s, doctors had been aware of a virus that was neither A nor B, but it was not until 1989 that hepatitis C was identified. Other viruses have been identified more recently.

Hepatitis A

Transmission: Contact with something, usually food or water, contaminated by the feces of an infected person.

Symptoms: Flu-like symptoms such as fatigue, abdominal pain, loss of appetite, nausea, diarrhea, dark urine, and jaundice (yellowing of the skin and eyes). But some infected people have no symptoms.

Treatment: Bed rest and increased intake of fluids. Infections can be prevented if immune globulin, which is a preparation of antibodies, is given within two weeks of exposure to the virus. Vaccines are available.

New infections per year: Up to 200,000

Hepatitis B

Transmission: Direct contact with infected blood or bodily fluids, such as from sharing drug needles or having *** with an infected person. Babies can be infected by their mothers during birth.

Symptoms: Jaundice, fatigue, abdominal and joint pain, loss of appetite, nausea, and vomiting. Can lead to cirrhosis of the liver and liver cancer, however most people infected with the virus do not develop chronic infection. Some people never develop symptoms.

Treatment: The drug interferon reduces the chance of a return of the disease and can be effective in about 30 percent to 40 percent of patients. A vaccine has been available since the early 1980s.

New infections per year: Between 150,000 and 300,000

Hepatitis C

Transmission: Shared drug needles, ***ual contact and blood transfusions prior to 1992. Babies can get the disease from their mothers during birth.

Symptoms: Most people never experience acute symptoms such as fatigue, abdominal pain, loss of appetite, jaundice, nausea, and vomiting. Can cause chronic liver damage, cirrhosis of the liver, and liver cancer.

Treatment: Interferon. When that is not effective, doctors try Rebetron, a combination of drugs made up of interferon and ribavirin. There is no vaccine.

New infections per year: Between 28,000 and 180,000

Hepatitis D

Transmission: Intravenous drug use, *** with an infected partner, and from mother to baby. But it can only be contracted by people who also are infected with hepatitis B.

Symptoms: Jaundice, fatigue, abdominal and joint pain, loss of appetite, nausea, and vomiting. Produces chronic liver-damage symptoms that are similar to hepatitis B only more severe.

Treatment: Interferon is used for some people. The vaccine for hepatitis B is effective in stopping the transmission of hepatitis D, too, but only in people who are not already infected with hepatitis B.

New infections per year: About 5,000

Hepatitis E

Transmission: Contaminated water from the feces of infected humans. It is not commonly contracted in the U.S.

Symptoms: Inflammation of the liver leading to loss of appetite, nausea and vomiting, fever, fatigue, and abdominal pain. Many people who contract it have no symptoms.

Treatment: No vaccine. Doctors encourage bed rest and drinking extra fluids.

New infections per year: Few U.S. cases



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