Cell Studies Shed Light on Liver Disease
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.

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