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Why Hepatitis Drug Works for Some People
By Nancy Touchette

The most promising drug for hepatitis B infection helps only one in four patients. Now, researchers in the United States and Italy have identified genetic changes in the hepatitis virus that can predict whether a patient will respond to the drug.

Transmission electron micrograph of hepatitis B virions.

The drug, lamivudine, is expensive, and the new findings could eventually help doctors decide who should use the drug and who should try alternative therapies. A third of the world’s population has been infected by the hepatitis B virus, which kills more than a million people each year.

The researchers detected two changes in a gene that codes for an essential enzyme in the hepatitis B virus. If the virus harbors either variation, lamivudine therapy is doomed to fail. But the drug efficiently kills “normal” viruses by blocking the enzyme, called DNA polymerase.

In a recent study, the researchers treated 26 people infected with hepatitis B virus with the drug. None of the seven patients who recovered completely had either variant. Half of the patients responded initially, but then relapsed, and the rest never improved.

“It’s an all or nothing response,” says John L. Gerin of Georgetown University’s Laboratory of Molecular Virology & Immunology in Rockville, Maryland, who led the study. “Of the patients who did not ultimately benefit from therapy, all had one of the polymorphisms in the polymerase gene.”

The findings were presented at the Annual Conference for Antiviral Research in Savannah, Georgia. The Georgetown group collaborated with researchers in Torino, Italy.

Brent Korba, another Georgetown researcher on the project, says the findings could help doctors and patients if confirmed by larger studies.

“Why give the drug to someone who won’t benefit?” he asks. “The drug is very expensive and once you start therapy, you have to stay on it for life.”

Most people infected with hepatitis B experience an initial acute phase, which usually clears on its own. But many are plagued with a chronic infection that lasts a lifetime. Hepatitis can ultimately cause cirrhosis of the liver, liver cancer, and death.

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