Hepatitis Patients at Risk of Developing Cirrhosis Identified

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.

The Stanford University (Stanford, CA, USA) group was one of three universities to determine that a genetic test can identify patients who are at high risk of developing cirrhosis from chronic hepatitis C infection. Management of cirrhosis patients is challenging, said Ramsey Cheung, M.D., associate professor of medicine at the school and chief of hepatology at the Palo Alto Veterans Affairs Health Care System (CA, USA), 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 (Rockville, MD, USA). Dr. Cheung is the senior author of the study, which will be published in the April 27, 2007, advance online issue of the journal Hepatology. Dr. Cheung is a 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 Dr. Cheung. Treatment includes weekly injections of alpha interferon along with the drug ribavirin, which can cost more than US$30,000 per year and can cause flu-like symptoms, nausea, depression, and other side effects. Only half of the 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.

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 Dr. 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 do not 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 cannot reveal how much future damage will occur.

The lead author of the paper is Hongjin Huang, Ph.D., associate director of liver diseases at Celera in Alameda, (CA, USA). Dr. 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 Dr. 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 the expense of current therapy.


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Stanford University
Celera