A researcher at the Stanford University School of Medicine has helped confirm the reliability of a new test for liver disease that is ushering in the long-promised era of personalized medicine based on each individual's genetic makeup.
The Stanford group was one of the five sites that helped determine that the genetic test can identify patients who are at high risk of developing cirrhosis from chronic hepatitis C infection. That means high-risk patients could be directed toward a long course of expensive, debilitating drug therapy, while low-risk patients might be better off delaying treatment.
"Management of cirrhosis patients is challenging," said Ramsey Cheung, MD, associate professor of medicine at the school and chief of hepatology at the Palo Alto Veterans Affairs Health Care System, who led the Stanford arm of the study. "This test is the first of its kind to use the genetic makeup of each patient to determine who is likely to develop cirrhosis. High-risk patients should be targeted for early treatment."
The test looks at variations of seven genes, and was developed by Celera, headquartered in Rockville, Md. Cheung is the senior author of the study, which will be published in the journal Hepatology. Cheung is a paid consultant for Celera, which also funded the study.
"Current therapy for hepatitis C unfortunately is very expensive, has multiple side effects and a suboptimal response rate for most patients," said Cheung. Treatment includes weekly injections of alpha interferon along with the drug ribavirin, which can cost more than $30,000 per year and can cause flu-like symptoms, nausea, depression and other side effects. And only half of patients undergoing this therapy will be cured of the infection.
Nearly 4 million Americans are infected with the hepatitis C virus, of which nearly 80 percent have a chronic infection, according to the American Liver Foundation. Chronic infection can lead to the severe scarring known as cirrhosis, which in turn may result in liver cancer or liver failure. Hepatitis C infection is the most common reason people need a liver transplant in the United States and is responsible for between 8,000 and 10,000 U.S. deaths annually.
But in the majority of people chronically infected with hepatitis C, the virus causes either no symptoms or vague, nonspecific ones. In around one-third of people chronically infected with the virus, the disease progression is slow and they may never develop cirrhosis, even after decades of infection.
The dilemma physicians face, explained Cheung, is deciding who to treat and who can wait for better therapies to come along. The key is being able to determine which patients are likely to see the infection progress to cirrhosis. Doctors consider such factors as age, gender and alcohol consumption to predict such risk, but because of individual variability, these factors don't yield a very accurate prediction. A liver biopsy can indicate the amount of damage to the liver up until the time of the biopsy, but can't reveal how much future damage will occur. The new test assessed by Cheung and his colleagues is a way to hedge the bets.
The lead author of the paper is Hongjin Huang, PhD, associate director of liver diseases at Celera in Alameda, Calif. Huang and her Celera colleagues developed the test by initially scanning the DNA of more than 1,000 people who had hepatitis C. Out of 25,000 genetic variations tested, the researchers discovered seven that could be used together as a "signature" for predicting progression to cirrhosis in Caucasians.
The resulting gene signature - the Cirrhosis Risk Score - was then independently validated on 154 hepatitis C patients at Stanford, the University of Illinois-Chicago and California Pacific Medical Center. Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.
"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."
Last June, Celera licensed Specialty Laboratories of Valencia, Calif., to perform the genetic test. The test currently costs about $500.
In addition to Cheung and Huang, the other 12 authors of the study are from Celera, Virginia Commonwealth University, Mount Sinai School of Medicine, California Pacific Medical Center, the University of Illinois-Chicago and the University of California-San Francisco.
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