Monday, August 17, 2009

New genetic discovery identifies which patients likely to benefit from Hepatitis C treatment

Hepatitis C affects approximately 170 million people worldwide, but only around 40 percent of people who seek treatment are likely to have the virus successfully eliminated.

But a huge new discovery has found a gene that indicates which patients with genotype 1 of the Hepatitis C virus (HCV) are most likely to have success with treatment, and it also provides insight into why different racial groups respond so differently to treatment.

The findings will likely help patients decide whether they want to pursue treatment, and could have a significant influence on the study design of future HCV trials. The standard treatment for HCV lasts 48 weeks, and frequently the side effects are so bad that some patients decide to stop treatment altogether. Knowing they have a much greater chance of success could help physicians and patients determine if they should consider HCV treatment.

“For geneticists, understanding response to treatment for hepatitis C infection has been almost like a Holy Grail,” says David Goldstein, PhD, director of the Center for Human Genome Variation in Duke's Institute for Genome Sciences & Policy and the senior author of the study. “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 findings were published online in Nature on August 16. The DCRI's Alexander Thompson, PhD, was one of the study's lead authors, and the DCRI's Andrew Muir, MD, and John McHutchison, MD, were co-authors on the paper.

“This stunning finding supports the integration of research efforts that previously were not connected,” says Robert Califf, MD, vice chancellor for clinical research and director of the DTMI. “The researchers have combined world class genotyping and clinical trials management in an academic medical center with an industry sponsored clinical trial to produce a set of findings that are likely to change practice. Their focus on modification of clinical outcomes is especially important to note as we design future studies.”

As part of the IDEAL study, patients were asked if they would consent to provide a sample of their DNA and more than 1600 agreed. Researchers found a genetic marker that significantly indicates whether treatment will be successful. Eighty percent of patients who had the marker had no signs of HCV in their systems following treatment, but only 30 percent of patients who did not have the gene had the virus successfully eradicated.

Another finding about the gene is that African-Americans are less likely to carry it, which offers some explanation as to why these patients have traditionally not responded as well to treatment compared to Caucasians.

“This discovery appears to explain a large part of it. It is most certainly a triumph of translational medicine,” said study co-author Dr. McHutchison, associate director of the DCRI and a member of the Division of Gastroenterology in the School of Medicine at Duke. “This is a perfect example of bedside to bench and back to bedside investigation.”

The marker that researchers found consists of a single letter change – a C instead of a T – in a tiny segment of DNA near the IL28B gene. The marker was more likely to appear in Caucasian patients, who make up a significant portion of the HCV population.

Researchers want to do future studies to test other genotypes of HCV, to see if patients who have different genotypes of the virus also have the genetic marker and if it indicates a similar success rate with treatment.

When diagnostic tests become available for patients to see if they have the genetic marker, researchers hope it will encourage more patients to get diagnosed and to consider treatment. HCV is a leading cause of cirrhosis of the liver and a significant contributor to why patients need liver transplants.

“These findings are an example of true translational research, and a great example of the rewards it can yield,” said Dr. Thompson.

Drs. Muir and Thompson both feel that this discovery is one of the most remarkable that they have come across in their careers, and they feel that it will have significant impact on many HCV patients around the world.

“This is absolutely one of the reasons why I went into clinical research. Working for an academic research center, with a world leader in Hepatitis C research in Dr. McHutchison and one of the world's leading geneticists in Dr. Goldstein, we are able to bring together clinical problems and the scientists who want to help improve care,” said Dr. Muir. “It is incredibly rewarding to be a part of it.”