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A Viral Illness That Can Be Silent and Hard to Treat but Also Cured

Hepatitis C can take decades to show up as damage to the liver.


Chronic viral hepatitis is now the leading reason for liver transplants.

Current combination therapy can be individualized to cure chronic infections in 40 to 80 percent of cases.

The consequences of being infected with hepatitis C can take years to appear. So while new cases of the disease have fallen sharply over the past few decades, many people infected years ago are only beginning to learn they carry the virus, and to grapple with its potentially serious effects.

For many, there is good news. Half of all chronic infections can now be cured through a therapy using a combination of drugs. But hepatitis C remains a wily virus, often lying low for years and then following a course so unpredictable that doctors sometimes aren’t sure whether to recommend treatment or advise patients to watch and wait.

The biggest obstacle to effective treatment remains the fact that a majority of the estimated 3.2 million Americans who harbor chronic hepatitis C aren’t even aware they have it. In four out of five people, there are no symptoms when the infection first occurs.

“Most of the people we see discovered they have chronic hepatitis C when they went to donate blood or had a physical exam in order to get insurance,” said Dr. Bruce R. Bacon, director of the division of gastroenterology and hepatology at Saint Louis University School of Medicine.

Almost a third of those exposed to hepatitis C recover fully; their immune systems rout the virus and eliminate it. About 70 percent develop chronic infections, which carry a significant risk of cirrhosis, or scarring, of the liver and liver cancer. Paradoxically, people who become sickest soon after being infected are most likely to fight off the virus, whereas those who have few if any initial symptoms are at greatest danger of suffering persistent infection.

The treatment currently recommended for chronic hepatitis C combines ribavirin, an antiviral drug, with interferon, a substance that increases the immune system’s virus-killing power. The treatment offers a lifelong cure for more than half of patients. But because the drugs are expensive and can have serious side effects, and because the course of disease varies so much from person to person, the decision to start therapy poses tough questions.

“About one-third of people with chronic hepatitis will go on to develop cirrhosis of the liver,” said Dr. Jay H. Hoofnagle, director of the Liver Disease Research Branch at the National Institutes of Health. “Only 5 to 10 percent will develop liver cancer. In other words, many people can live perfectly well with chronic hepatitis infection and never have any problems. The trouble is we can’t tell who will do well and who will die of the disease.”

Nor can doctors predict with certainty how patients will respond to the combination therapy. In 25 to 30 percent of patients, interferon produces anxiety and depression, sometimes so extreme that sufferers have attempted suicide. It can also cause debilitating flu-like symptoms.

“I can usually get anyone through two or three months of interferon and ribavirin. Beyond that, it gets really tough,” Dr. Hoofnagle said. “At least 10 percent of patients can’t make it through the recommended course of therapy.”

Fortunately, physicians are getting better at optimizing the benefits and controlling some of the unwanted side effects, thanks in part to new insights into the virus. Researchers have discovered that hepatitis C occurs in at least six forms, called genotypes. Genotype 1 is the most common and also the hardest to treat, requiring 48 weeks of treatment. Only about 40 percent of people with this subtype get rid of the virus. Genotypes 2 and 3 can be successfully treated in just 24 weeks, eliminating the virus in about 80 percent of cases.

The more rapidly virus levels begin to fall in patients, the better the odds of a cure. By monitoring levels of the virus in blood, some doctors say, it’s now possible to individualize the course of treatment.

“I call it the accordion effect,” said Dr. Ira Jacobsen, chief of the division of gastroenterology and hepatology at Weill Cornell Medical College in New York. “If virus levels drop off very quickly, we can shorten the course of therapy. If the response is slow, we can lengthen it, sometimes to as much as 72 weeks, and improve the chances of success.”

Shortening the course of therapy remains controversial because of the risk of relapse after the treatment is stopped. Relapse occurs when lingering viruses not eradicated by the medication multiply and surge back.

Antidepressant drugs, meanwhile, are being employed to ease psychiatric side effects. And doctors are getting better at predicting who will suffer depression after starting interferon.

“Not surprisingly, people with a history of depression are at greater risk,” said Dr. Francis Lotrich, assistant professor of psychiatry at the University of Pittsburgh. He and his colleagues have also observed that people with chronic sleep problems are also more likely to have trouble with depression. The reason is not clear, but studies are under way to see if improving people’s sleep with the use of insomnia medication or other techniques can lower the risk of psychiatric side effects.

The best medicine is prevention, and it’s here that the biggest gains have been won against hepatitis C. The number of new infections per year in the United States has plummeted from 240,000 in the 1980s to about 19,000 in 2006. Experts credit a screening test that now prevents hepatitis C from spreading via blood transfusions and organ transplantation, as well as public health messages aimed at discouraging the use of shared needles, which is the leading route of transmission.

In the absence of an effective vaccine, such messages, backed up by intensified surveillance, will remain the chief defense against this virus. In 2003, chronic hepatitis B and C became notifiable diseases that must be reported to federal health officials, enabling them to track new cases nationwide. In 2004, New York State began its own enhanced viral hepatitis surveillance network.

Two years ago, the program demonstrated its usefulness when officials in the Erie County Department of Health detected a cluster of cases centered in one zip code in suburban Buffalo.

“All we had at first was a bunch of dots on a map,” said Dr. Anthony J. Billittier IV, the Erie County health commissioner. Investigators went into the community and identified about 20 young people who were injecting drugs and sometimes sharing needles. The county responded by intensifying prevention efforts, including a free needle exchange.

“We’ve made a lot of progress against hepatitis C, but there’s still a lot to do,” Dr. Billittier said. “One one thing we know about this virus is it’s not going away.”

Sources: The New York Times

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