Warren Grant Magnuson Clinical Center
"Hepatitis C is a devastating disease that exacts a significant toll in this
country and abroad, and whose full clinical impact has yet to be realized,"
states Anthony S. Fauci, M.D., director of the National Institute of Allergy
and Infectious Diseases (NIAID) at the NIH. "This research helps to explain
how the virus manages to persist in the body and provides physicians with a
potential way to predict the development of a chronic infection."
Nearly 4 million Americans have been infected with the hepatitis C virus
(HCV). Of those who contract hepatitis C, 85 percent remain chronically
infected, harboring a virus that continues to replicate throughout a
person's life. HCV is a major cause of chronic liver disease and is
responsible for a third of all cases of cirrhosis and liver cancer, half of
all liver transplants, and 8,000 to 10,000 deaths in this country annually.
Patrizia Farci, M.D., and Robert Purcell, M.D., of NIAID and Harvey Alter,
M.D., of the NIH Warren Magnuson Clinical Center, led a team of scientists
in a study designed to see whether the hepatitis C virus changes during
infection. Dr. Alter had been conducting long-term studies of patients who
contracted hepatitis from blood transfusions. These individuals
subsequently developed different clinical outcomes, ranging from short-term
infections to chronic disease. Some of these patients have had hepatitis C
for over 20 years. "This unique group was critical for our study, because
they had been observed continuously since early in infection," states Dr.
Farci, who splits her time between NIAID in the United States and the
University of Cagliari in Italy.
Three of the 12 patients studied had acute HCV infections, three had
fulminant hepatitis (a rare but serious form of acute disease), and six had
chronic hepatitis. The research team examined the virus in each person,
looking specifically for changes in the genes that encode special proteins
coating the viral surface. They also studied what changes occurred either
before or after the body's immune system responded to HCV infection.
In some patients, the virus remained relatively unchanged following the
initial immune response, and those people completely eliminated HCV over
several weeks. In most, however, genetic HCV variants began to appear in
response to the early immune assault. This rapid viral evolution ultimately
resulted in chronic infection.
"We know that the body responds to infection early in the disease process,
but in most patients the virus is 'smarter' than the immune system," states
Dr. Farci. "In many cases, HCV changes its surface proteins as soon as the
patient's antibodies begin to attack. In essence, the virus slips into a
disguise and continues on without detection."
Similar masquerades are used by other viruses, such as HIV and influenza,
but this is the first study to correlate such behavior with disease
progression in hepatitis C. The researchers also determined a region on
virus surface proteins where most of the changes occur. Their studies will
now focus on the types of mutations that assist HCV in avoiding the immune
system, and on the types of antibodies produced during the early response.
By understanding more about this critical checkpoint in HCV infection, they
hope to develop new tools for hepatitis C treatment and prevention.
Other collaborators from NIH, University of Cagliari, Kanazawa University
(Japan), Chiron Corporation, and Albert Einstein Medical Center participated
in this study.
NIAID is a component of the National Institutes of Health (NIH). NIAID
conducts and supports research to prevent, diagnose and treat illness such
as HIV disease and other sexually transmitted diseases, tuberculosis,
malaria, asthma and allergies. NIH is an agency of the U.S. Department of
Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.