Drinking May Worsen Hepatitis C Infection

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.

Alcohol Affects the Hepatitis C Virus

"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 journal 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.

Naltrexone Blocks Alcohol's Effects

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.

Major Cause of Cirrhosis

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.

Source: University of Philadelphia.

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