Finding the right combination to fight hepatitis C

Of the millions of Americans infected with hepatitis C, only half respond to treatment. The others live with the constant threat that their health may suddenly, and fatally, deteriorate.

A new drug could improve those odds. When used with the antiviral drug interferon, a medication called Zadaxin may help thousands of patients better fight the disease.

“This medication looks promising for people who don’t respond to other drugs,” says Dr. Sammy Saab, a liver specialist at UCLA’s David Geffen School of Medicine. “It may also be used as part of a combination drug cocktail for all hepatitis C sufferers, since it seems to work by a different mechanism of action than other medications.”

About 4 million Americans are infected with hepatitis C, and about 2.7 million of those have an active infection, in which the liver is inflamed. Infection is insidious, however. People can be symptom-free for years, but the virus can quietly incubate, causing cirrhosis of the liver, liver cancer or even liver failure. Hepatitis C, which kills 10,000 people a year, is the leading reason for liver transplants in the U.S.

The current treatment -- a combination of two antiviral medications, interferon and Ribavirin -- helps only about half of those with active infections and less than a third who are infected with the more prevalent and more dangerous form of hepatitis C, known as genotype 1.

The drugs also have serious side effects, leading many people to stop taking them. Ribavirin can cause anemia, which leaves patients feeling extremely fatigued, while interferon can cause flu-like symptoms and birth defects if taken by pregnant women. These side effects “can result in having to reduce the dose and therefore decrease the efficacy of the drugs,” says Dr. Adrian Di Bisceglie, a liver specialist at St. Louis University School of Medicine in Missouri.

Zadaxin has no apparent side effects. It is a synthetic version of thymosin alpha 1, a naturally occurring protein that circulates in the body and stimulates the production of certain immune system cells. Zadaxin is approved for sale in 30 countries as an antiviral drug to treat hepatitis B but in only a few countries to combat hepatitis C.

Results of a 2002 U.S. study of the drug as a hepatitis C therapy were encouraging. The test involved 31 patients who had high levels of genotype 1 and who hadn’t responded to standard medications. Zadaxin, used in combination with interferon, greatly reduced levels of the virus in up to 36% of the patients.

The findings were especially significant because patients who don’t respond to the initial round of treatment seldom benefit from subsequent therapy.

“We purposely chose the most difficult of the most-difficult-to-treat patients,” says Di Bisceglie, who conducted this research. The drug is in the final phase of U.S. trials.

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About the disease

Hepatitis C is one of five identified viruses -- hepatitis A, B, C, D and E -- that attack and damage the liver. Hepatitis C, however, is considered the most grave and is spread mostly through contact with infected blood.

Before a test was available for hepatitis C, some people were unwittingly infected through blood transfusions. Others acquired it by injecting illegal drugs, receiving organs from donors whose blood contained the virus, getting pricked with a needle that had infected blood on it, snorting cocaine using shared equipment, getting a tattoo or body piercing with non-sterile instruments or through sexual activity.

Although Zadaxin may help treat the virus, other drugs -- which aren’t as far along in development -- may ultimately vanquish it. Among the more promising are hepatitis C protease inhibitors, which work by blocking the action of a key enzyme that the virus needs to replicate. Drugs that have a similar mechanism of action, disabling protease, revolutionized AIDS treatment.

Other experimental medications include a monoclonal antibody that latches onto the surface of the HCV (HCV-AB68), preventing the virus from entering the cells, and a fusion protein (albuferon), which may enhance the action of interferon.