Alcohol increases hepatitis C virus in human cells

June 26, 2003

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:

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 NF-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 IFN-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 IFN-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 NF-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.
-end-
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 http://www.niaaa.nih.gov.

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.

NIH/National Institute on Alcohol Abuse and Alcoholism

Related Alcohol Articles from Brightsurf:

Alcohol use changed right after COVID-19 lockdown
One in four adults reported a change in alcohol use almost immediately after stay-at-home orders were issued: 14% reported drinking more alcohol and reported higher levels of stress and anxiety than those who did not drink and those whose use stayed the same.

Changes in hospitalizations for alcohol use disorder in US
Changes over nearly two decades in the rate of hospitalizations and in-hospital deaths from alcohol use disorder in the US were examined in this study.

Associations of alcohol consumption, alcohol-induced passing out with risk of dementia
The risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers was examined in this observational study with more than 131,000 adults.

New alcohol genes uncovered
Do you have what is known as problematic alcohol use?

Does estrogen influence alcohol use disorder?
A new study from researchers at the University of Illinois at Chicago shows that high estrogen levels may make alcohol more rewarding to female mice.

Sobering new data on drinking and driving: 15% of US alcohol-related motor vehicle fatalities involve alcohol under the legal limit
A new study in the American Journal of Preventive Medicine, published by Elsevier, found that motor vehicle crashes involving drivers with blood alcohol concentrations (BACs) below the legal limit of 0.08 percent accounted for 15% of alcohol-involved crash deaths in the United States.

Alcohol-induced deaths in US
National vital statistics data from 2000 to 2016 were used to examine how rates of alcohol-induced deaths (defined as those deaths due to alcohol consumption that could be avoided if alcohol weren't involved) have changed in the US and to compare the results by demographic groups including sex, race/ethnicity, age, socioeconomic status and geographic location.

Cuts in alcohol duty linked to 2000 more alcohol-related deaths in England
Government cuts to alcohol taxes have had dramatic consequences for public health, including nearly 2000 more alcohol-related deaths in England since 2012, according to new research from the University of Sheffield's School of Health and Related Research (ScHARR).

Integrated stepped alcohol treatment for people in HIV care improves both HIV & alcohol outcomes
Increasing the intensity of treatment for alcohol use disorder (AUD) over time improves alcohol-related outcomes among people with HIV, according to new clinical research supported by the National Institutes of Health.

The Lancet:Targets to reduce harmful alcohol use are likely to be missed as global alcohol intake increases
Increasing rates of alcohol use suggest that the world is not on track to achieve targets against harmful alcohol use, according to a study of 189 countries' alcohol intake between 1990-2017 and estimated intake up to 2030, published in The Lancet.

Read More: Alcohol News and Alcohol Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.