Medical Forum / Diseases and Disorders / Hepatitis / November 2009
Sexual Transmitted HCV
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Nyarnon - 30 Oct 2009 18:38 GMT Thank God we have waterspider to declare officially that there is no mounting evidence for HCV being an STD. And thank god we have our faithfulls working in the prisons explaining there that hcv is not an STD. Now spread the holy Gospel *HCV is no STD*. And while your at it tell everybody how good coffee is for them. Sigh.
http://www.reuters.com/article/pressRelease/idUS187872+30-Oct-2009+PRN20091030
New Epidemic of Sexually Transmitted Hepatitis C Infection in HIV-infected Men in NYC Presentation: Sunday, November 1, 2009, 8:00 am Eastern Time in Boston, MA
ALEXANDRIA, Va. and BOSTON, Oct. 30 /PRNewswire/ -- Researchers in New York City are reporting their work uncovering a new epidemic of hepatitis C virus (HCV) infection among men-who-have-sex-with-men (MSM) who have HIV infection. These authors have previously reported unusually rapid fibrosis progression due to new HCV in MSM who have HIV infection and now expand on their findings, demonstrating that sexual transmission rather than injection drug use is the route of infection. Treatment is highly successful if started early in the course of infection, however, they report ominous news about liver disease progression. "This epidemic represents a new clinical syndrome for HCV infection that turns much of our knowledge on its ear: a new risk group becoming infected through a previously rare route of transmission resulting in unprecedented progression of liver fibrosis," said Daniel Fierer, MD, principal investigator on this study.
In an analysis of 21 HCV-infected patients matched with uninfected controls, unprotected receptive anal and oral sex were significantly associated with new HCV infection. Neither current nor prior injection drug use was associated with HCV infection. In addition, treatment with pegylated interferon and ribavirin, initiated within 6 months of diagnosis, was completed in 16 patients with genotype 1 HCV infection; 12 (75%) achieved sustained viral response (SVR), compared to the 15-30% SVR rate expected with chronic genotype 1 HCV infection. Of significant concern, however, 30 patients underwent liver biopsy during the early infection period and 23 (77%) already had moderate fibrosis, making early curative treatment even more important to prevent further progression of liver fibrosis.
Because of these findings, study authors recommend routine screening for acute HCV for all MSM patients with HIV, using a simple and inexpensive algorithm of ALT measurement every 3 months and HCV antibody measurement every 6 to 12 months. "Changing the perception and behavior of physicians and patients is difficult," said Dr. Fierer, "One of the main barriers to early detection is the lack of recognition by physicians and patients alike that HIV-infected MSM are at risk for HCV infection. This lack of perception of the problem results in lack of screening of HIV-infected MSM and therefore lack of timely diagnosis and treatment."
Dr. Fierer thinks the next steps in battling this epidemic are educating HIV providers about the existence of this world-wide epidemic, educating patients at risk that unprotected sex among HIV-infected men is a significant risk for HCV infection, and changing the official recommendations by the US national authorities such as the CDC, HIVMA, etc, as has already been done in Europe and more recently at the state level in New York.
Abstract title: Characterization of an epidemic of sexually-transmitted acute hepatitis C infection in HIV-infected men in New York City
About the AASLD
AASLD is the leading medical society focused solely on advancing the science and practice of hepatology and represents more than 3,300 practitioners, researchers, and allied health professionals worldwide. Founded by physicians in 1950, AASLD has upheld the standards of the profession and fostered research that generates treatment options for the millions of patients with liver diseases.
This year's Liver Meeting, held in Boston, Massachusetts, October 30 - November 3, will bring together more than 7,000 researchers from 55 countries. A pressroom will be available from October 31 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Tracy at 703-299-9766.
Press releases, additional information for the media, and all abstracts are available online at www.aasld.org.
Media Contact: Gregory Bologna 703/299-9766 gbologna@aasld.org
Press Room: October 31 - November 3, 2009 Hynes Convention Center, Room 209 Telephone: (617) 954-2827
Researcher: Daniel Fierer, MD Email: daniel.fierer@mssm.edu Phone: (212) 824-7413
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com
SOURCE American Association for the Study of Liver Diseases (AASLD)
Gregory Bologna, +1-703-299-9766, gbologna@aasld.org
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Waterspider unmasked http://groups.google.com/group/alt.support.hepatitis-c/msg/987c5a3337fe148d?dmod e=source
M - 30 Oct 2009 19:42 GMT > Thank God we have waterspider to declare officially that there is no > mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 14 lines] > (HCV) infection among men-who-have-sex-with-men (MSM) who have HIV > infection. Snip.
Sounds like it could be a blood to blood sex trip to me.
M
Thip - 30 Oct 2009 20:59 GMT >> Thank God we have waterspider to declare officially that there is no >> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 21 lines] > > M Because of these findings, study authors recommend routine screening for acute HCV for all MSM patients *with HIV*
And this has what to do with a female prison?
Waterspider - 30 Oct 2009 21:32 GMT >>> Thank God we have waterspider to declare officially that there is no >>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 27 lines] > > And this has what to do with a female prison? Best not to question the logic of Nyranon... it's a dark and twisty place to go ;-)
Thip - 30 Oct 2009 21:47 GMT >>>> Thank God we have waterspider to declare officially that there is no >>>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 29 lines] > Best not to question the logic of Nyranon... it's a dark and twisty place > to go ;-) Yeah, I know better. Who was it that said, "You cannot win an argument with an ignorant man"?
CatEyes - 30 Oct 2009 21:56 GMT >>>>> Thank God we have waterspider to declare officially that there is no >>>>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 32 lines] > Yeah, I know better. Who was it that said, "You cannot win an argument > with an ignorant man"? Same person who said it's no fun to have a battle of wits with an unarmed opponent? ;>
Hugs,
CatNipped
Waterspider - 30 Oct 2009 21:57 GMT >>>>> Thank God we have waterspider to declare officially that there is no >>>>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 32 lines] > Yeah, I know better. Who was it that said, "You cannot win an argument > with an ignorant man"? I rather like Shakespeare's, "I would challenge to a battle of wits, but I see you are unarmed!"
Seriously, many of this guy's comments are both dangerous and offensive. I'd hate to see some newbie have a look at the board, read some of his misinformation and base important decisions on it. He does have some knowledge, but not nearly as much as he thinks he has, and that's a bad combination. Otherwise, I'd simply plonk him.
CatEyes - 30 Oct 2009 22:00 GMT >>>>>> Thank God we have waterspider to declare officially that there is no >>>>>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 40 lines] > knowledge, but not nearly as much as he thinks he has, and that's a bad > combination. Otherwise, I'd simply plonk him. No worries about this newbie, it took me about 3 posts to determine how seriously to take his "advice".
Hugs,
CatNipped
dBo - 31 Oct 2009 19:31 GMT > No worries about this newbie, it took me about 3 posts to determine how > seriously to take his "advice". [quoted text clipped - 4 lines] > > - Show quoted text - “I learned long ago, never to wrestle with a pig, you get dirty; and besides, the pig likes it.” (George Bernard Shaw)
Good quote to keep in mind when Riba rage has people going off like rockets.... (yeah, I'll give them the benefit of the doubt and blame it on Riba Rage)
Thip - 31 Oct 2009 00:38 GMT >>>>>> Thank God we have waterspider to declare officially that there is no >>>>>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 40 lines] > knowledge, but not nearly as much as he thinks he has, and that's a bad > combination. Otherwise, I'd simply plonk him. Good point, but I've got enough going on without having to put up with his crap. I'll leave the battle to you.
Nyarnon - 31 Oct 2009 11:15 GMT Thip schreef:
>>>>>>> Thank God we have waterspider to declare officially that there is >>>>>>> no mounting evidence for HCV being an STD. And thank god we have [quoted text clipped - 43 lines] > Good point, but I've got enough going on without having to put up with > his crap. I'll leave the battle to you. Kewl, one thread collecting all the trolls at once. Showing how instead of a single argument they go straight into the defensive by personal defamation. Great work guys love it :-)
When your all done don't forget to stamp your little troll feet and shout HCV IS NOT A STD. And maybe you can also post a few of those messages saying that I say it is, even if I'm not.
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tom - 31 Oct 2009 14:10 GMT > Kewl, one thread collecting all the trolls at once. Pot-Kettle-Black
Dwight - 31 Oct 2009 20:09 GMT >> Thank God we have waterspider to declare officially that there is no >> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 22 lines] > > M Nyarnon, all bow to your infinite wisdom. HCV is not an STD. It can only be spread through blood to blood contact. (That is not the definition of an STD.) Never mind, you won't be able to consider the possibility that you may be wrong so there is no point in even trying to explain things to you.
Dwight
Nyarnon - 31 Oct 2009 21:24 GMT Dwight schreef:
>>> Thank God we have waterspider to declare officially that there is no >>> mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 30 lines] > > Dwight You could start with a peer reviewed paper proving it is not. As it stands I produced several papers now that show mounting evidence it is while the only thing I get back on f.i. this paper is a brainless comment HCV is not a STD and a lot of kids crying how big and bad Nyarnon is. Common man try to impress me with something substantial? If you can make a statement like that you must be able to support that?
And how can I be wrong? Where did I ever say it is a STD? In fact I state in almost every message that I am not saying it is one. How hard is that to observe?
Again my beef is with people who state it isn't, creating a false sence of security out there. Because HCV is blood to blood transmittable it doesn't exclude that it is a STD.
In fact we are having the same discussion, amongst adults who respect eachothers point of view and share facts instead of flames, on the nomad board. Some info came up about HIV/HCV co-infected. I'm waiting for the paper but it seems that in coinfected persons HCV is able to piggyback ride the transmission channel for HIV.
Where this is relevant you might ask? Well there is a tendency among male homosexuals who have HIV to find a partner that has HIV because of the better mutual understanding. No safe sex needed your both infected and Waterspider says HCV is no STD. Fact is that this is now becoming a new stigma under the homosexuals. And HCV is flourishing.
Thats the damage that is created right here, by saying HCV is no STD. That is what I am fighting against without claiming that it is one. Yet. Why is it so hard just not to say that until you can prove it beyond doubt?
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Waterspider - 01 Nov 2009 01:00 GMT > You could start with a peer reviewed paper proving it is not. You cannot prove that something does *not* exist; you can only prove that it *does* exist. Your repeated demand for such a paper is impossible to meet, but it is hardly proof that HCV is an STD.
As it
> stands I produced several papers now that show mounting evidence Mounting evidence is not proof. And I guess "mounting evidence" that HCV is an STD isn't a play on words...
it is
> while the only thing I get back on f.i. this paper is a brainless Brainless? Brainless is asking for proof that something doesn't exist.
> comment HCV is not a STD and a lot of kids crying how big and bad Nyarnon > is. In your dreams, honey. We're just banging our heads on the wall, saying, "It's not rocket science, why can't he get it?"
> Common man try to impress me with something substantial? If you can make a > statement like that you must be able to support that? > > And how can I be wrong? Where did I ever say it is a STD? In fact I state > in almost every message that I am not saying it is one. How hard is that > to observe? What's disturbing is that you say it isn't... and then you argue that it is.
> Again my beef is with people who state it isn't, creating a false sence of > security out there. Because HCV is blood to blood transmittable it doesn't > exclude that it is a STD. Malaria is a blood-borne virus. Do you consider malaria to be an STD?
> In fact we are having the same discussion, amongst adults who respect > eachothers point of view and share facts instead of flames, on the nomad > board. Some info came up about HIV/HCV co-infected. I'm waiting for the > paper but it seems that in coinfected persons HCV is able to piggyback > ride the transmission channel for HIV. I'm curious; just what does that mean? The bit about, in coinfected persons, HCV piggyback riding the HIV transmission channel."
> Where this is relevant you might ask? Well there is a tendency among male > homosexuals who have HIV to find a partner that has HIV because of the > better mutual understanding. No safe sex needed your both infected and > Waterspider says HCV is no STD. Fact is that this is now becoming a new > stigma under the homosexuals. And HCV is flourishing. Are you suggesting that I'm suggesting people in general and HIV patients in particular, shouldn't practice safe sex? Wow.
> Thats the damage that is created right here, by saying HCV is no STD. That > is what I am fighting against without claiming that it is one. Yet. Just to clarify: you're saying that HCV is no STD, but damage is being done because we're saying that HCV is no STD and, even though it is no STD, it may become one?
> Why is it so hard just not to say that until you can prove it beyond > doubt? Because it's wrong. Because of the stigma caused by the association between HCV and STDs. Because of the stigma caused by the association between HCV and HIV. But mostly, because it's wrong.
Thip - 01 Nov 2009 01:12 GMT > I'm curious; just what does that mean? The bit about, in coinfected > persons, HCV piggyback riding the HIV transmission channel." Easy. HVC is blood-borne and HIV can be blood-borne. Ergo, "piggyback riding the HIV transmission channel" means both of them can travel in the blood.
My goodness, Spidey, how simple is that? Sheesh! ;-)
Waterspider - 01 Nov 2009 01:00 GMT >> I'm curious; just what does that mean? The bit about, in coinfected >> persons, HCV piggyback riding the HIV transmission channel." [quoted text clipped - 4 lines] > > My goodness, Spidey, how simple is that? Sheesh! ;-) I guess I got hung up on the part about coinfection, wondering if Nyarnon was saying that it provided a brand-new transmission channel not available if either virus was absent. Piggyback does imply that one relies on the other for transportation. This would mean that one could contract hep C from someone with HIV, where they would not have if the HIV was absent. At least I think that's what it means. Nasty little virii no matter how you interpret it.
Happy Hallowe'en :-)
Nyarnon - 01 Nov 2009 02:28 GMT Waterspider schreef:
>>> I'm curious; just what does that mean? The bit about, in coinfected >>> persons, HCV piggyback riding the HIV transmission channel." [quoted text clipped - 13 lines] > > Happy Hallowe'en :-) You may admire the size difference between HIV and HCV here: http://learn.genetics.utah.edu/content/begin/cells/scale/
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Nyarnon - 01 Nov 2009 02:02 GMT Waterspider schreef:
>> You could start with a peer reviewed paper proving it is not. > You cannot prove that something does *not* exist; you can only prove that it > *does* exist. > Your repeated demand for such a paper is impossible to meet, but it is > hardly proof that HCV is an STD. Well I am getting tired to say so but one more time I'm not trying to proof it is one. Never said it is one. And if you cannot proof it is not an STD you shouldn't say so. Simple as it gets. Your argument that you cannot proof something does not exist is not valid here as STD's do exists they are clearly defined and all you have to do is show beyond doubt that HCV does not fit that definition.
> As it >> stands I produced several papers now that show mounting evidence >> > Mounting evidence is not proof. And I guess "mounting evidence" that HCV is > an STD isn't a play on words... Proof of what? Please dont say that it is a std becouse I will have to reitterate with the comment that nobody is trying to proof it is. The farest I am willing to go at this moment is mounting evidence that HCV possibly could be an STD.
> it is >> while the only thing I get back on f.i. this paper is a brainless > Brainless? Brainless is asking for proof that something doesn't exist. Nobody ask you to proof something does not exist as I explained above.
>> comment HCV is not a STD and a lot of kids crying how big and bad Nyarnon >> is. > In your dreams, honey. We're just banging our heads on the wall, saying, > "It's not rocket science, why can't he get it?" Yes I can see that now. You don't get it. And I am obviously unable to express myself in a understandable way.
>> Common man try to impress me with something substantial? If you can make a >> statement like that you must be able to support that? [quoted text clipped - 4 lines] >> > What's disturbing is that you say it isn't... and then you argue that it is. OK now we have something substantial show me where I argue that it is?
>> Again my beef is with people who state it isn't, creating a false sence of >> security out there. Because HCV is blood to blood transmittable it doesn't >> exclude that it is a STD. >> > Malaria is a blood-borne virus. Do you consider malaria to be an STD? Have I stated anywhere that blood borne diseases are STD?
>> In fact we are having the same discussion, amongst adults who respect >> eachothers point of view and share facts instead of flames, on the nomad [quoted text clipped - 4 lines] > I'm curious; just what does that mean? The bit about, in coinfected persons, > HCV piggyback riding the HIV transmission channel." I will tell you as soon as I have received the paper. I'm very curious myself and I know that if I would give you a deeper explanation now you would explode and this discussion would be over.
>> Where this is relevant you might ask? Well there is a tendency among male >> homosexuals who have HIV to find a partner that has HIV because of the [quoted text clipped - 4 lines] > Are you suggesting that I'm suggesting people in general and HIV patients in > particular, shouldn't practice safe sex? Wow. No I don't Im suggesting that you saying it is not an STD makes the likelihood bigger for people to ignore safe sex. People dont want safe sex if they think they can avoid it they will. I do not believe that you would purposely bring people in that danger but the end result is not very much different. Just because you are unwilling to temporarily put an doctrine on halt that is currently becoming scrutinized.
I understand what you are saying what you are trying to protect, but that is not your call. People have to be allowed to make up their own mind you shouldn't make that decision for them by presenting a doctrine that you cannot prove.
>> Thats the damage that is created right here, by saying HCV is no STD. That >> is what I am fighting against without claiming that it is one. Yet. >> > Just to clarify: you're saying that HCV is no STD, No I cannot say that as I do not have conclusive evidence to make such a statement.
> but damage is being done > because we're saying that HCV is no STD and, Yes because you have no conclusive evidence to advice people in that way.
> even though it is no STD, You still have to proof that.
> it > may become one? No it cannot become that, it can be determined to be one. It that case it will always have been one. Like the flat earth theory, when proven to be round the earth didn't become round it always was round.
>> Why is it so hard just not to say that until you can prove it beyond >> doubt? >> > Because it's wrong. Why would that be wrong? Is it a religious thing?
> Because of the stigma caused by the association between HCV and STDs. That stigma is there and by defending unholdable doctrines without an argument you will not prevent that.
> Because of the stigma caused by the association between HCV and HIV. You wont stop that the casus of the Gay community shows that, wait here another one, page 77 please:
http://www.gscene.com/pdf/gsceneapril2008.pdf
> But mostly, because it's wrong. So it is a religious thing. I'm so sorry it must be hard to stand on the brink of loosing a god or confirm him for that matter. Nailbiting so to speak.
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Paul - 31 Oct 2009 15:23 GMT On Fri, 30 Oct 2009 17:38:42 +0000, Nyarnon <roelfrenkema@gmail.com>,
>Thank God we have waterspider to declare officially that there is no >mounting evidence for HCV being an STD. And thank god we have our >faithfulls working in the prisons explaining there that hcv is not an >STD. Now spread the holy Gospel *HCV is no STD*. And while your at it >tell everybody how good coffee is for them. Sigh. Well I suppose that if someone has had HCV as very long time it could mean that their liver is f.cked. However, I'm not sure that's what's meant by it being an STD. Also, how long have Nescafé been funding HCV research? :-)
Thip - 31 Oct 2009 15:36 GMT > Well I suppose that if someone has had HCV as very long time it could > mean that their liver is f.cked. However, I'm not sure that's what's > meant by it being an STD. > Also, how long have Nescafé been funding HCV research? :-) ROFL!!!!
I thought it was Starbucks?
Nyarnon - 31 Oct 2009 16:18 GMT Paul schreef:
> On Fri, 30 Oct 2009 17:38:42 +0000, Nyarnon <roelfrenkema@gmail.com>, > [quoted text clipped - 8 lines] > meant by it being an STD. > Also, how long have Nescafé been funding HCV research? :-) Hahaha yes the research is probably fueled by coffee so in the end it might indeed be good against HCV,
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Waterspider - 31 Oct 2009 17:35 GMT > On Fri, 30 Oct 2009 17:38:42 +0000, Nyarnon <roelfrenkema@gmail.com>, > [quoted text clipped - 5 lines] > Well I suppose that if someone has had HCV as very long time it could > mean that their liver is f.cked. LOL!
Cactus Jammies - 04 Nov 2009 16:41 GMT are you being thick-skulled purposely? oh, and please read the Milk Thistle discussion thread about what really counts when you take it. It's in the compound in the seed. Silymarin is refined to a concentrate for the IV experiments on viral load reduction before standard treatment is started.
cactus jammies ~~~~~~~~~~~~~ at least this isn't crossposted to the whole frakkn world
> Thank God we have waterspider to declare officially that there is no > mounting evidence for HCV being an STD. And thank god we have our [quoted text clipped - 124 lines] > > Gregory Bologna, +1-703-299-9766, gbologna@aasld.org Nyarnon - 04 Nov 2009 23:34 GMT Cactus Jammies schreef:
> are you being thick-skulled purposely? oh, and please read the Milk > Thistle discussion thread about what really counts when you take it. > It's in the compound in the seed. Silymarin is refined to a concentrate > for the IV experiments on viral load reduction before standard treatment > is started. I hate to be the one to bring this to you but you realy should stop spelling the commercials. Milk Thistle has been used for over 2000 years against liver disease. Now some pharmas come decide to pick out a few things call it Silymarin, put in on *alcohol* and that it?
Yes a few things Silimarin is a combo.
Please consider f.i. that the seed is full of fibers. How do they interact with your liver in the silymarin? Right they don't. Another example are probioticts. Are you using probiotics?
http://news.bbc.co.uk/2/hi/health/8286646.stm
Why do I mention that? Like the Silymarin the probiotics in f.i. actimel are a cheap worthless copy of the real thing:
http://en.wikipedia.org/wiki/Kefir
Go buy your bottle of concentrated Silymarin. And do believe everyone who tells you the seed is useless for your liver, it has only been used for 2000 years for that purpose.
BTW The IV experiment was sponsored by the only company allowed to produce the German medical version of Silymarin. Sure they will tell you the seed won't work.
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Cactus Jammies - 07 Nov 2009 19:12 GMT > BTW The IV experiment was sponsored by the only company allowed to produce > the German medical version of Silymarin. Sure they will tell you the seed > won't work. .........................................
ummmm.... buddy. you don't seem to read very well. first of all Silymarin is the way it is spelled on the label of the bottle of milk thistle capsules sitting in front of me. and I never said that the actual non-concentrate, the ground milk thistle seed is useless. I wrote that you need both, if you care to look up a few postings. It performs other functions and is a part of the stuff in the capsules I use. But one without the other is not what you want. Such as you grinding your own. Sure it may reduce inflammation in your liver (which it does, or lowers your alt/ast) but it doesnt get into your bloodstream to depress the viral load count. which is not a bad thing. and which is what the Silymarin (silimbum?) compound apparently does do. do.
this is stressful. I am booking out of this particular string.
cactus jammies
Nyarnon - 07 Nov 2009 21:00 GMT Cactus Jammies schreef:
>> BTW The IV experiment was sponsored by the only company allowed to >> produce the German medical version of Silymarin. Sure they will tell [quoted text clipped - 17 lines] > > cactus jammies I never said you said that, they said that and I just added it as an illustration that I think they have a special intrest in having people avoid the thistle in favor of there product. In fact today NATAP gives us more of the same crap. Again a university, France this time and who is involved again? Cologne.
Notice how Milk Thistle this time is avoided like the plague? Now it thrives on the new buzzword INHIBITOR. Kewl.
NATAP http://natap.org/ _______________________________________________
Silibinin and Related Compounds are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase
Reported by Jules Levin AASLD Oct 31-Nov 3 2009, Boston, MA
A. Ahmed-Belkacem1; N. Ahnou1; L. Barbotte1; C. Wychowski2; R. Brillet1; R. Pohl3; J. Pawlotsky1
1. Henri Mondor Hospital, University of Paris 12, Creteil, France.
2. Institut de Biologie de Lille, Lille, France.
3. Madaus-Rottapharm, Cologne, Germany.
Only approximately 50% of patients with HCV genotype 1 infection eradicate infection upon pegIFN-ribavirin therapy. Current HCV drug discovery efforts focus on developing molecules that specifically inhibit HCV enzymes, such as the RNA-dependent RNA polymerase (RdRp) or the NS3/4A protease. Silymarin is a mixture of flavonolignans extracted from the milk thistle, which contains several molecules including silibinin A, silibinin B, isosilibinin A, isosilibinin B, silichristin, and silidianin. Intravenous infusion of Legalon SIL®, a commercially available preparation of silibinin, induces dose-dependent reduction of HCV RNA levels. Our aim was to test the isomers contained in silymarin preparations for their ability to inhibit HCV enzymatic functions and replication in different models.
METHODS: The inhibitory activity of silymarin components was tested in HCV RdRp and NS3/4A protease enzyme assays. Their ability to inhibit replication of an HCV genotype 1b replicon and the JFH1 infectious HCV model in cell culture was also studied. The effect of amino acid substitutions known to confer HCV resistance to RdRp inhibitors was tested.
RESULTS: Silibinin A, silibinin B, their water-soluble dihydrogen succinate forms and Legalon SIL®, a commercially available intravenous preparation of silibinin, inhibited HCV RNA-dependent RNA polymerase function, with inhibitory concentrations 50% (IC50s) of the order of 75-100 micromolar. Silibinin A and silibinin B also inhibited HCV genotype 1b replicon replication with effective concentrations 50% (EC50s) of the micromolar order, and HCV genotype 2a strain JFH1 replication in cell culture with EC50s approximately one log above those observed in the replicon system. None of the tested silymarin components showed any inhibitory activity in the NS3/4A protease assay, up to a concentration of 200 µM. No cytotoxic effect was observed at inhibitory concentrations in two different human cell lines (Huh7 and HEK 293). Amino acid substitutions known to confer resistance to RdRp inhibitors, including 2?-methyl nucleoside analogues (S282T) and non-nucleoside inhibitors (P495L, M423T, H95Q, and C316Y, located in thumb 1, thumb 2, palm 1 and palm 2 RdRp domains, respectively) did not confer resistance to silibinin in the RdRp enzyme assay.
CONCLUSIONS: Silibinin A and silibinin B, as well as Legalon SIL®, inhibit HCV replication in cell culture. This effect is at least partly explained by the ability of these compounds to directly inhibit HCV RdRp activity. These results provide a basis for the optimization and subsequent development of members of the Flavonoid family as specific HCV antivirals.
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