How alcohol use may worsen hepatitis C infection

June 26, 2003

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.
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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 he 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.

Children's Hospital of Philadelphia

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