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U.S. Department of Health and Human Services
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Date Posted: Sun, July 13 2003, 12:06:56 PDT
In reply to:
Arch Intern Med 2002
's message, "Smoking and alcohol consumption are independently associated with disease progression" on Wed, April 17 2002, 7:52:29 PDT
U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
http://www.niaaa.nih.gov/
FOR IMMEDIATE RELEASE Thursday, June 26, 2003
Contact:
NIAAA Press Office (301) 443-0595 (301) 443-3860
ALCOHOL INCREASES HEPATITIS C VIRUS IN HUMAN CELLS
Drinking May Compromise Treatment Success
A team of NIH-supported researchers today report that alcohol increases
replication of the hepatitis C virus (HCV) in human cells and, by so doing,
may contribute to the rapid course of HCV infection. The researchers tested
the actions of alcohol in HCV replicon - viral HCV-
ribonucleic acid or HCV-RNAs that, when introduced into human liver cell
lines, replicate to high levels. In separate laboratory experiments they
showed that
-- alcohol increases HCV replication at least in part by upregulating a key
cellular regulator of immune pathways and function known as nuclear factor
kappa B;
-- alcohol inhibits the anti-HCV effect of interferon-alpha therapy; and
-- treatment with the opioid antagonist naltrexone abolishes alcohol
actions.
Wenzhe Ho, M.D., and Steven D. Douglas, M.D., Department of Pediatrics,
University of Pennsylvania, and the Joseph Stokes, Jr. Research Institute at
The Children's Hospital of Philadelphia, and colleagues in the Department of
Psychiatry, University of Pennsylvania School of Medicine report their
results in the July 2003 issue of "Hepatology"
(Volume 38, Number 1, pages 57-65).
Speculating that alcohol somehow promotes HCV expression, the researchers
relied on a recently available cellular system for studying the dynamics of
virus replication (developed and provided to the investigators by Drs. C. M.
Rice, The Rockefeller University, and Christoph Seeger, Fox Chase Cancer
Center) to demonstrate for the first time that alcohol enhances HCV replicon
expression at both the messenger RNA and protein levels. In the cell lines
used for the study, the research team also showed that alcohol activation of
nuclear factor kappa B was responsible for increasing HCV expression.
"Although the replicon system mimics only some aspects of HCV replication,
we have identified at least a likely mechanism whereby alcohol increases
viral load and thus may become an important cofactor in HCV severity," Dr.
Douglas said.
"These findings are immediately useful to clinicians for counseling
HCV-positive patients about alcohol use," said Ting-Kai Li, M.D., Director,
National Institute on Alcohol Abuse and Alcoholism (NIAAA). "For clinical
and basic scientists, they raise new research questions, many of which no
doubt will be explored using the model and methods introduced today." NIAAA
supported the experiments through a grant to Dr. Douglas, whose work also
was supported by the National Institute of Mental Health and the National
Institute on Drug Abuse (NIDA). The NIAAA and NIDA supported Dr. Ho's work
on the study.
HCV is an RNA virus of the flavivirus family that infects about 4 million
U.S. residents and produces some 30,000 new infections each year. HCV
typically escapes clearance by the immune system and leads to persistent,
chronic infection in 70 to 85 percent of infected individuals, of whom fewer
than 50 percent respond to interferon-alpha, the HCV therapy of choice. Over
the long term, HCV infection can lead to cirrhosis, liver failure, and liver
cancer. As a group, HCV-infected individuals are the major recipients of
liver transplantation.
Clinicians have long observed a high incidence of HCV infection in heavy
drinkers, including those without other risk factors such as intravenous
drug abuse or history of blood transfusions. In addition, the virus is more
likely to persist in heavy drinkers and to lead to such complications as
cirrhosis and liver cancer. Suspected mechanisms for the latter effects
include alcohol's capacity to compromise immune function and enhance
oxidative stress. The role of alcohol use in HCV acquisition has been more
of a mystery.
During the 1990s, several studies reported higher blood levels of HCV in
drinkers than abstainers and in habitual than infrequent drinkers. Further,
drinking reduction was shown to diminish the number of virus particles in
the blood. These observations led Dr. Douglas and his colleagues to pursue
the role of alcohol in HCV replication.
Using the same replicon, Drs. Ho, Douglas and their colleagues also
demonstrated that alcohol compromises interferon-alpha action against HCV
and explored a plausible mechanism for alcohol's role in HCV expression.
Alcohol interferes with endogenous opiates, which have a key role in its
addictive properties. The researchers found that the opiate receptor
antagonist naltrexone, better known for its utility in helping alcoholism
treatment patients to avoid relapse, not only blocked the promoting effect
of alcohol on HCV expression but also diminished alcohol activation of
nuclear factor kappa B in these cells. "These data strongly suggest that
activation of the endogenous opioid system is implicated in alcohol-induced
HCV expression," the authors conclude.
For an interview with Dr. Douglas, please telephone (215)
590-1978; for an interview with Dr. Ho, please telephone (215) 590-4462. For
an interview with NIAAA staff members, please contact the NIAAA Press
Office. Publications and additional alcohol research information are
available at .
The National Institute on Alcohol Abuse and Alcoholism, a component of the
National Institutes of Health, U.S.
Department of Health and Human Services, conducts and supports approximately
90 percent of U.S. research on the causes, consequences, prevention, and
treatment of alcohol abuse, alcoholism, and alcohol problems and
disseminates research findings to science, practitioner, policy making, and
general audiences.
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