August 17, 2009

Gene Predicts Poor HCV Treatment Response in Blacks

Lack of a favorable genetic polymorphism (like a mutation) in people with Hepatitis C virus (HCV) predicts about 50 percent of all HCV treatment failures, according to a study published online August 16 in Nature. Because blacks are less than half as likely to have the favorable gene than white and Hispanic patients, this goes a long way toward explaining why they respond a lot less frequently to HCV treatment.

One unexplained difference in HCV treatment rates has been in black patients. A number of studies, though not all, have found that black patients also respond less well than white patients. While some of the difference in treatment response among black study participants could be explained by a variety of factors, such as higher HCV viral loads before starting therapy and a higher likelihood of having HCV type 1, these did not explain all of the difference. Researchers have long suspected that there might be genetic differences between black and white or Hispanic people with HCV, and the newly published Nature study describes exactly that.

Dongliang Ge, PhD, from Duke University in Durham, North Carolina, and his colleagues looked at gene sequences from more than 1,600 patients with HCV from several HCV treatment studies. None of the patients were also infected with HIV. Ge’s team found that a polymorphism near the IL28B gene significantly enhanced a person’s response to HCV treatment. Those without the genetic polymorphism did much more poorly.

This link between the polymorphism and a favorable treatment response held true regardless of race. Not having the polymorphism reduced a person’s chances of responding to treatment by 50 percent. The proportion of people having the polymorphism, however, varied significantly depending on race.

More than 50 percent of white and Hispanic participants and 70 percent of East Asian participants in the studies had the polymorphism. Far fewer black patients, however—just over 20 percent—had the favorable polymorphism. In other words, blacks are a lot less likely to have the polymorphism that helps a person respond well to treatment. Thus, it appears that genetics, not race, describes most of the treatment response differences.

Ge and his colleagues estimate that the genetic polymorphism predicts the poorer treatment response in blacks about half the time. Combined with the other factors associated with a poor response in the various studies—such as higher HCV viral loads—which were more likely in black patients, this could explain much of the difference in treatment responses by race observed so far.

Given the magnitude of the difference in treatment response, the authors state that testing for this genetic polymorphism in the future could be an important factor in deciding in whom, and how, to initiate HCV treatment. Future studies, however, will be necessary to confirm their finding, especially in individuals coinfected with HCV and HIV.

NEW! Scroll down to comment on this story.

Previous Comments: