New Test Helps Identify Hepatitis C Patients at High Risk of

New Test Helps Identify Hepatitis C Patients at High Risk of Developing Cirrhosis

STANFORD, CA -- April 27, 2007



-- 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 April 27 advance online issue of 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% 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, CA. 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.