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HCV infection in heavy alcohol users. Interesting Study.
I have long speculated that heavy alcohol use might just cause some sort of 'activation' of the HCV virus in certain persons that might have a suppressed, or latent form of the virus somewhere in their systems. Possibly this heavy alcohol use could cause the emergence of a full blown, chronic HCV infection, newly detectable by standard blood testing. I just came across this NIH study, and article from a few years ago, which appeared in Hepatology. Notice, way down in the article, the comments about researchers confusion over alcohol's role in the acquisition of HCV. They refer to those without other risk factors, and still seem to have not been able to clarify why there is such a disproportionate number of alcoholics who become HCV positive. Remember, these are alcoholich who have no IVDU or transfusion history. My idea is that some people probably do carry a subdetectable HCV virus, that is kept under immune system control, and is not provoking a humoral antibody response. These might be the people who 'come down with HCV' after chronic heavy drinking. Just my explanation of this riddle. Here is the article:
Alcohol Increases Hepatitis C Virus in Human Cells
Drinking May Compromise Treatment Success
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
alcohol increases HCV replication at least in part by upregulating a key cellular regulator of immune pathways and function known as nuclear factor kappa B (NF-κB);
alcohol inhibits the anti-HCV effect of interferon-alpha (INF-α) therapy; and
treatment with the opioid antagonist naltrexone abolishes alcohol actions.
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-κB 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-α, 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-α 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-κB in these cells. "These data strongly suggest that activation of the endogenous opioid system is implicated in alcohol-induced HCV expression," the authors conclude.
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 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.
--------------------------------------------------------------------------------
Alcohol Increases Hepatitis C Virus in Human Cells
Drinking May Compromise Treatment Success
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
alcohol increases HCV replication at least in part by upregulating a key cellular regulator of immune pathways and function known as nuclear factor kappa B (NF-κB);
alcohol inhibits the anti-HCV effect of interferon-alpha (INF-α) therapy; and
treatment with the opioid antagonist naltrexone abolishes alcohol actions.
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-κB 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-α, 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-α 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-κB in these cells. "These data strongly suggest that activation of the endogenous opioid system is implicated in alcohol-induced HCV expression," the authors conclude.
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 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.
--------------------------------------------------------------------------------
Enter a major trigger (heavy alcohol use, morphine/ opiate use, etc, as the article relates), and BAM, just like Chef Emeril you have the full blown Souffle!
I believe that you are right and it's a personally sensible thing. If you think about it your immune system I guess would be so busy working out all that **** out of your body that it might lessen its grip while the alcohol or drugs was helping it to replicate.
They were talking about bed bugs this morning on the news and said they can CARRY HepB / HIV but not transmit it. I thought hey why not? They said that the hep would stay alive for at least one hour after they bit the host. So I guess it's back to the question "if a mosquito can transmit malaria why not HIV or HEP" - just meaning it gave me pause to wonder how many ways can you actually GET HepC that they don't really know about yet.
I mean are the SURE?
All in all a very great article and discussion.
I believe that you are right and it's a personally sensible thing. If you think about it your immune system I guess would be so busy working out all that **** out of your body that it might lessen its grip while the alcohol or drugs was helping it to replicate.
They were talking about bed bugs this morning on the news and said they can CARRY HepB / HIV but not transmit it. I thought hey why not? They said that the hep would stay alive for at least one hour after they bit the host. So I guess it's back to the question "if a mosquito can transmit malaria why not HIV or HEP" - just meaning it gave me pause to wonder how many ways can you actually GET HepC that they don't really know about yet.
I mean are the SURE?
All in all a very great article and discussion.
hmmm...all of this seems like a pretty convincing argument to stay off the booze if I ever svr.
I am basically stating the second explanation that you described. That there are people with the virus already in their systems, but undetected, and in a more or less dormant state. The alcohol would trigger the virus into a full blown infection.
I also leave room for how they got the virus 'into' their systems initially, since I think there is not enough understanding on the realm of possibilities for this, at this point. Could a person receive the virus through a compartmentalized transmission (fluids, birth transmission, sexual, etc.) in which the virus does not trigger any humoral antibody alarms, but remains silently replicating in a contained reservoir? There is already huge research evidence that the virus exists and replicates in lymphatic glands and cells, potentially also in salivary glands, etc. So possibly there could be a 'cellular' level transmission that remains contained by the cellular immune system, and only becomes a full blown systemwide infection after some major triggering event....like the alcohol abuse behaviors described in the research article...which then allow the previously contained, compartmentalized virus to replicate. Maybe there are mechanisms for controlling minute amounts of virus in the body, as in SVR's and spontaneous clearers, where the person no longer appears to be infected, and has no PCR load, BUT the virus indeed is able to be found in very small amounts, in some compartments in the body, over many years.
My conjecture is that there may be others out there exposed in some way to the virus, that have never suffered the "Acute" infection, and whose system has already quickly contained and suppressed any exposure to the virus, and now holds it in-check in an ongoing basis. Enter a major trigger (heavy alcohol use, morphine/ opiate use, etc, as the article relates), and BAM, just like Chef Emeril you have the full blown Souffle!
So, maybe there are people scattered throughout the population in small or large percentages, who have already been exposed to the virus, may have small amounts in their systems with no viral load, and no detectable antibodies in the blood, who will never suffer an HCV infection as we know it, UNLESS they experience some triggering event. Maybe this is why so many people who have absolutely no IVDU, transfusions, surgeries, tattoos, etc. get diagnosed with HCV and literally have no idea how they could have gotten it. And maybe this also is why so many more alcohol abusers seem to get infected than the rest of the 'non-alcohol-abusing population.
I hope this clearly explains my comments, and some of the conjecture that I have added regarding the research article.
DoubleDose
I also leave room for how they got the virus 'into' their systems initially, since I think there is not enough understanding on the realm of possibilities for this, at this point. Could a person receive the virus through a compartmentalized transmission (fluids, birth transmission, sexual, etc.) in which the virus does not trigger any humoral antibody alarms, but remains silently replicating in a contained reservoir? There is already huge research evidence that the virus exists and replicates in lymphatic glands and cells, potentially also in salivary glands, etc. So possibly there could be a 'cellular' level transmission that remains contained by the cellular immune system, and only becomes a full blown systemwide infection after some major triggering event....like the alcohol abuse behaviors described in the research article...which then allow the previously contained, compartmentalized virus to replicate. Maybe there are mechanisms for controlling minute amounts of virus in the body, as in SVR's and spontaneous clearers, where the person no longer appears to be infected, and has no PCR load, BUT the virus indeed is able to be found in very small amounts, in some compartments in the body, over many years.
My conjecture is that there may be others out there exposed in some way to the virus, that have never suffered the "Acute" infection, and whose system has already quickly contained and suppressed any exposure to the virus, and now holds it in-check in an ongoing basis. Enter a major trigger (heavy alcohol use, morphine/ opiate use, etc, as the article relates), and BAM, just like Chef Emeril you have the full blown Souffle!
So, maybe there are people scattered throughout the population in small or large percentages, who have already been exposed to the virus, may have small amounts in their systems with no viral load, and no detectable antibodies in the blood, who will never suffer an HCV infection as we know it, UNLESS they experience some triggering event. Maybe this is why so many people who have absolutely no IVDU, transfusions, surgeries, tattoos, etc. get diagnosed with HCV and literally have no idea how they could have gotten it. And maybe this also is why so many more alcohol abusers seem to get infected than the rest of the 'non-alcohol-abusing population.
I hope this clearly explains my comments, and some of the conjecture that I have added regarding the research article.
DoubleDose
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.
-------------------------------------
I've always believed that this is how many of us who were more than "casual" drinkers could reach a high stage in the same amount of time as another who does not drink. Increasing the replication raises the liver enzymes and voila....major cell death and increasing stages. Duh, easy point.
Of course - there can be people who treat and completely annhiliate the virus and are truly UND, then there can be others who "appear" to be completely UND - are not - go back to drinking and the virus springs back into heavy replication.
Once again it would seem to be to be completely subjective to what is going on in the persons particular body - true UND or not. SVR would therefore mean to me "under control barring no unforeseen complications" - meaning you could have virus - albeit undetectible levels of it but still have systemic virological response - but NOT truly be UND.
Then the virus would have the perfect opportunity if one were to imbibe and not truly be UND (compared to SVR) and begin its replicating wonderland of freefall.
I hope that made some sort of sense. SVR with TRUE UND level of ZERO or SVR with UND levels. And I guess since there is no test that sensitive one could never know until it's too late.
-------------------------------------
I've always believed that this is how many of us who were more than "casual" drinkers could reach a high stage in the same amount of time as another who does not drink. Increasing the replication raises the liver enzymes and voila....major cell death and increasing stages. Duh, easy point.
Of course - there can be people who treat and completely annhiliate the virus and are truly UND, then there can be others who "appear" to be completely UND - are not - go back to drinking and the virus springs back into heavy replication.
Once again it would seem to be to be completely subjective to what is going on in the persons particular body - true UND or not. SVR would therefore mean to me "under control barring no unforeseen complications" - meaning you could have virus - albeit undetectible levels of it but still have systemic virological response - but NOT truly be UND.
Then the virus would have the perfect opportunity if one were to imbibe and not truly be UND (compared to SVR) and begin its replicating wonderland of freefall.
I hope that made some sort of sense. SVR with TRUE UND level of ZERO or SVR with UND levels. And I guess since there is no test that sensitive one could never know until it's too late.
I am very confused. Are you saying that drinking might CAUSE the hcv virus to spontaneously appear? I hope not because spontaneous generation was debunked by Louis Pasteur in the 19th century, and his findings are the cornerstone of microbiology and germ theory (remember biology class).
Or are you saying that people can walk around with a tiny amount of virus in their system which alcohol helps replicate and then become chronic? This seems probable considering all of the people that 'clear' the virus on their own. I think that people experiencing alcohol seemingly causing the hcv infection could be from this group of people that cleared the virus initially. That makes sense to me, but then they still had to get the initial infection from a blood to blood contact right?
This harks back to the good old debate as to whether are bodies ever really get rid of the virus completely.
Anyway, please clarify, because it seems like you are proposing both scenarios...
Or are you saying that people can walk around with a tiny amount of virus in their system which alcohol helps replicate and then become chronic? This seems probable considering all of the people that 'clear' the virus on their own. I think that people experiencing alcohol seemingly causing the hcv infection could be from this group of people that cleared the virus initially. That makes sense to me, but then they still had to get the initial infection from a blood to blood contact right?
This harks back to the good old debate as to whether are bodies ever really get rid of the virus completely.
Anyway, please clarify, because it seems like you are proposing both scenarios...
I just said that Schiff's explanation -- per my quote -- seemed more plausible -- so you must admit I have good company :) That doesn't mean I'm selectively throwing out anything or even discounting what you are theorizing. I DO keep an "open and keenly inquisitive mind" or so I tell women at bars (sipping diet coke, of course) trying to
impress:) Hope this finds you well, and please keep the thoughts coming but please also accept respectful alternative/counter theories, as hopefully mine are presented.
-- Jim
impress:) Hope this finds you well, and please keep the thoughts coming but please also accept respectful alternative/counter theories, as hopefully mine are presented.
-- Jim
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