How Alcohol Use May Worsen Hepatitis C Infection; Cell Studies Shed Light on Liver Disease

06/26/2003

PHILADELPHIA, June 26 /PRNewswire/ -- Immunology researchers have
demonstrated that alcohol promotes the proliferation of hepatitis C virus in
human liver cells. By studying molecular mechanisms in cell cultures, the
researchers help explain the role of alcohol in aggravating hepatitis C
infection and interfering with drug treatment for the infection.

Infecting some 170 million people worldwide, hepatitis C virus is one of
the leading known causes of liver disease in the United States.

"It was already known that habitual alcohol drinkers have higher blood
levels of hepatitis C virus, compared to infrequent drinkers, even when both
are infected with the virus," said Wen-Zhe Ho, M.D., the director of
retroviral research at The Children's Hospital of Philadelphia, who led the
research team. "We investigated how alcohol affects the hepatitis C virus at
the cellular level. Our study provides a biological mechanism to support
clinical observations." The study appears in the July issue of Hepatology.

The researchers found that alcohol increases the activity of a protein
called nuclear factor kappa B, and thereby causes the hepatitis C virus to
replicate, or produce multiple copies of itself. That protein is an important
cellular regulator of gene products involved in inflammation. Furthermore,
they found that alcohol interferes with the antiviral activity of interferon-
alpha, a key therapy used for patients infected with hepatitis C.

A third finding that may eventually have implications for patient
treatment was that naltrexone, a drug used to help patients with alcoholism
avoid relapse, may also block the deleterious effects of alcohol in promoting
hepatitis C infection.

The current research builds on previous research by the Children's
Hospital team, which found that morphine also stimulates hepatitis C virus in
liver cells by the same mechanisms as those found with alcohol.

Both alcohol and morphine activate opioid systems present in liver cells,
according to Dr. Ho. These systems contain biological pathways that produce
natural opiates that may play a crucial role in drug and alcohol addiction.

This process may explain why naltrexone, which blocks opiates from binding
to their receptors on cell membranes, reduced the effects of alcohol in the
current study. "Although further study is needed, our results suggest that
naltrexone might supply additional benefits in reducing hepatitis C
infection," said Dr. Ho.

Approximately 4 million people in the United States are infected with
hepatitis C virus, which is a major cause of cirrhosis and liver cancer, as
well as the most common reason for liver transplantation. The only licensed
treatment for the infection is interferon-alpha, but this is not permanently
effective in a majority of patients. There is no effective vaccine against
the virus either, so any interventions that reduce the activity of the virus
could have considerable benefit, said Steven D. Douglas, M.D., chief of
Immunology at The Children's Hospital of Philadelphia, and the principal
investigator of the study.

Co-authors with Drs. Douglas and Ho are Ting Zhang, M.D., Yuan Li, M.D.,
and Jian-Ping Lai, M.D., of the Division of Allergy and Immunology at
Children's Hospital, and David S. Metzger, Ph.D., and Charles P. O'Brien,
M.D., Ph.D., both of the Center for Studies of Addiction at the University of
Pennsylvania (Dr. O'Brien is director of that Center). The study was
supported by grants from the National Institutes of Health, specifically from
the National Institute on Alcohol Abuse and Alcoholism, the National Institute
of Mental Health and the National Institute on Drug Abuse.

Founded in 1855 as the nation's first pediatric hospital, The Children's
Hospital of Philadelphia is ranked today as the best pediatric hospital in the
nation by a comprehensive Child magazine survey. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 381-bed hospital recognition as a leading advocate for children
and adolescents from before birth through age 19. For more information, visit
http://www.chop.edu.

CONTACT: John Ascenzi, The Children's Hospital of Philadelphia,
+1-215-590-7332, Ascenzi@email.chop.edu.