Genetic Marker Predicts Response to Hepatitis C Treatment

A genome-wide association study found that the coding at a single site on DNA was responsible for differences in people's response to treatment for hepatitis C virus (HCV) infections. This finding will be used to develop a genetic test that will help physicians decide whether patients should undergo standard treatment for the infection. The test would not be used to deny anyone treatment, but rather to determine the patient's best options.

The genetic marker not only predicted who is most likely to respond to hepatitis C treatment and who is not, but also appears to explain why there are different rates of response among racial and ethnic groups, a phenomenon that has puzzled physicians for many years.

The new marker is a single letter change--a C (cytosine) instead of a T (thymine)--in a tiny segment of DNA near the IL28B gene. Duke University (Durham, NC, USA) scientists discovered the change when they studied 1671 individuals who participated in the individualized dosing efficacy vs. flat dosing to assess optimal pegylated interferon therapy (IDEAL) study--a multi-center clinical trial that compared two widely used therapies among patients with hepatitis in the U.S. and Europe.

Dr. Goldstein, director of the center for human genome variation at Duke's Institute for Genome Sciences and Policy (Durham, NC, USA), and colleagues found that patients who had the single-letter change in their DNA were significantly more likely to respond to treatment than those without it. "Eighty percent of those with the favorable response genotype eradicated the virus, while only about 30 % with the less favorable response genotype did so. With differences of that magnitude, patients considering therapy may want to know what their genotype is before they start treatment," said Dr. Goldstein, senior author of the study.

Hepatitis C is one of the most common infections in the world, affecting an estimated 170 million people. Many can live with the disease for years without serious complications. However, in about one quarter of infected people, hepatitis C leads to cirrhosis of the liver, which, in turn, can lead to liver cancer, death, or the need for a transplant. Hepatitis C is the leading cause for liver transplants in the United States.

The standard treatment for infection with the hepatitis C virus is a 48-week course of the antiviral drugs interferon and ribavirin that gives some patients flu-like symptoms and severe depression. The treatment varies in its effectiveness, being more successful in Americans of European descent than in African-Americans.

"For geneticists, understanding response to treatment for hepatitis C infection has been almost like a Holy Grail," noted Dr. Goldstein, "The side effects of hepatitis treatment can be brutal, and about half the time, the treatment fails to eradicate the virus. This discovery enables us to give patients valuable information that will help them and their doctors decide what is best for them. This is what personalized medicine is all about."

The study was reported online in the August 16, 2009, edition of the journal Nature.

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Duke University
Duke's Institute for Genome Sciences and Policy