Gene predicts response to hepatitis C drugs: study

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A slight difference in a person’s genetic code could determine whether they respond to a grueling round of treatment for hepatitis C infection or not, U.S. researchers said on Sunday.

Tests looking for that deviation could be used to help decide which patients are most likely to benefit, they said. The finding may also explain why some racial and ethnic groups fare more poorly on standard treatments than others.

“This discovery enables us to give patients valuable information that will help them and their doctors decide what is best for them,” genetics researcher David Goldstein of Duke University in Durham, North Carolina, said in a statement.

Hepatitis C is a blood-borne liver disease that can lead to chronic liver problems, liver cancer, Cirrhosis and death. The virus affects an estimated 3.2 million people in the United States alone and 170 million worldwide.

Treatment typically involves 48 weeks of interferon plus the antiviral drug ribavirin. Some patients develop such taxing side effects that they stop treatment. Blacks are less likely to respond than whites.

Until now, no one has known why.

‘SPELLING MISTAKE’

According to Goldstein’s study, published in the journal Nature, it may be because of a “spelling mistake”—a one-letter error in the genetic code near the Interleukin-28B or IL28B gene, which plays a role in fighting off infections.

“If you look at individuals with the good response genotype, about 80 percent of them will be cured. If you look at individuals with the poor-response genotype, about 30 percent of them will be cured,” Goldstein said in a telephone interview. “That is just a huge, huge difference.”

The discovery came from a clinical trial of 1,671 people with the most common form of the disease in the United States and Europe who were taking the two most common hepatitis C therapies.

It was funded by Schering-Plough, maker of one of two standard hepatitis C regimens—a combination of Pegintron and the antiviral ribavirin. Roche Holding AG makes the other, known as Pegasys.

They found having a favorable genotype made a significant difference in treatment response across all populations in the study, but because it occurs most often in whites of European ancestry, it helps explain why blacks fare less well on standard treatments.

Goldstein said few discoveries involving inherited genetic variations are specific enough to guide treatment decisions, but he thinks this is one.

“It is very difficult for me to imagine this wouldn’t be something that both the patient and the clinician would want to know about in deciding on a course of treatment,” he said.

“Right now, absent genetic information, if a patient comes into the clinic and they have no signs of liver damage, a decision is often reached to postpone treatment because the treatment is unpleasant and it often doesn’t work.”

He said the finding does not mean poor responders should not be offered therapy but it may alter their decision-making.

Goldstein said patients who are poor responders to standard treatments who have no liver damage might want to wait for the arrival of a new class of drugs called protease inhibitors.

The drugs are now in mid-stage development by Schering-Plough and Vertex Pharmaceuticals Inc.

By Julie Steenhuysen
CHICAGO (Reuters)

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