Hepatitis C remission due to drinking again

[artesian]

About 13 years ago my father had cirrhosis of the liver which led to Hepatitis C.  He recovered from the disease and became healthy. He completely stopped drinking for about 10 years, but has started drinking again in the past two or three years. At first it was just a little here or there...a glass or wine or a beer, but has now become a daily habit. He has even started drinking hard liquor, which seems worse although it is technically the same amount of alcohol. Anytime we make a comment, he tells us to give him a break.  He doesn't get drunk, but because of his history we are all uncomfortable with him drinking PERIOD.

The question I am hoping someone out there can help me with is does his resumed drinking increase the changes that his cirrhosis or hepatitis will come back? I would imagine so, but am hoping for some studies or statistics on the matter so I can show it to him. I would greatly appreciate any response...thank you.

[CoWriter]

You have it backwards.....Cirrhosis of the liver does NOT lead to Hepatitis C.  Hepatitis C is caused by a virus and it's transmitted from blood contact....meaning if somehow, infected blood got into his blood.  Risk factors include blood transfusions, IV drug use, tattoos, body piercings, etc.

Hepatitis C (as well as alcohol use) can cause cirrhosis.   The fact that he stopped drinking probably helped his liver, but cirrhosis doesn't really go away by itself.  Successful treatment for Hepatitis C sometimes reverses some of the damage.  

Some people can clear the Hepatitis C virus on their own in the first six months after getting infected....but if your father had Hepatitis C for longer than 6 months, then he probably still has it.

Alcohol use doubles the rate of liver damage progression and it can make the Hepatitis C virus multiply.  And if he already has cirrhosis, getting decompensated and needing a liver transplant in the future is a real possibility if he continues drinking.  
  

[Grace724]

Co writer is exactly right...HepC can lead to Cirrhosis. Cirrhosis does not cause HepC.

While it is possible to clear HepC on your own, that is not the norm. Most people don't even know they have HepC until they've had it for years. At that point the only way to rid yourself of HepC is to go on treatment that last many weeks. If your Dad has not done this...he still has HepC.

The 10 yr. hiatus of alcohol probably gave your Dad's liver a reprieve from the harsher symptoms of cirrhosis but it's doubtful that it eradicated it. Now that he is drinking again, he is pretty much throwing himself out of the frying pan and into the fire. His drinking will only cause more harm to his liver. His HepC will rev up and then he'll have that attacking his liver as well as the alcohol. A double whammy.

Does your Dad or did he see a Gastroenterologist or a Hepatologist? If not, he needs to see one soon. He needs to have his labs done, especially a liver panel to check his liver enzymes. He also needs to have the appropriate tests to check his HepC to see where he stands there in terms of viral load. I would also think he would need a liver biopsy, fairly simple procedure done on an out patient basis. The liver biopsy will tell him what the state of his liver is as far as Stage, which is the amount of damage to the liver and Grade which will indicate the level of necrosis (scarring) of the liver and the amount of inflammation.

Most of all he needs to have his doctor thoroughly educate him as to what alcohol is doing to his body and his chances of living a long life.

Good luck.

[artesian]

Thank you for updating my medical knowledge about the disease. Maybe I had the facts backwards, but I know my father no longer has Hepatitis C due to many months of giving himself shots, and was completely cleared by his doctor many years ago of the disease.

My question was in regards to any studies or statistics that prove starting to drink again will increase the likeliness of Hep C returning...that is our fear.

[jmjm530]

The question I am hoping someone out there can help me with is does his resumed drinking increase the changes that his cirrhosis or hepatitis will come back?

As suggested, your facts are incorrect.

(1) Cirrhosis does not cause Hepatitis C but hepatitis C can  cause Cirrhosis.

(2) You cannot "recover" from Hepatitis C. Either your cured or you still have it.

(3) Drinking alcohol does not cause Hepatitis C.

(4) As to your question, his resumed drinking will not bring Hepatitis C back, although from your statements it's unclear if your father really has it and/or he really got rid of it. That said, his drinking could seriously harm him if he has cirrhosis.

-----------------
I suggest your father see  liver specialist (hepatologist) and find out what is really going on. Both with the Hep C and cirrhosis.

The specialist will probably run a viral load test to see if he has Hepatitis C or not. Equally important, he will evaulate your father's liver condition in terms of how much damage he has and come up with a plan moving forward.

-- Jim

[jmjm530]

Our posts crossed.

From what you say, it appears your father once had Hep C and was cured with treatment.

And while drinking won't bring back the Hep C, it can potentially can do even more damage depending on how much he drinks and what the condition of his liver is today.

Again, a good liver specialist (hepatologist) should be able to evaluate his condition and point both of you in the right direction.

-- Jim

[CoWriter]

I disagree with jmjm.  After successful treatment for hepatitis C, small amounts of virus are left and it is believed that if your immune system at some points gets suppressed, the virus can become active again.  And alcohol is an immune-suppressant.

[jmjm530]

Co: I disagree with jmjm.
----------------------------------
You mean to say that you disagree with my doctors and our resident doctor here per his two posts. Had my docs told me "no alcohol" then I might just have had no alcohol.

As far as "small amounts of virus" being left -- without debating that point -- there areno cases I'm aware of where HCV has been "activated" post treatment by alcohol or any other means. The exception being 2-3 cases of postulated relapse due what I remember to be serious steroid therapy. to If you have any studies that suggest alcohol can reactivate Hep C, please post. But no quizzes :)

-- Jim

[DoubleDose]

The issue that you discuss above, re-activation of the virus after achieving SVR, is a controversial subject that has not received sufficient long term study, other than statistical studies of SVR's, which show that about 98% of SVR's remain virus free over five to ten years.  There are also a small number of those who 'relapse' after one or two years, after having been SVR, (the two percent above) and this is where the controversy becomes very cloudy.

Many claim that the late relapsers were never really SVR at all, but just appeared to be clear of the virus (whatever that means), and others claim that they must have been re-infected with a brand new infection.  The third camp believes that a this very tiny group of late relapsers have somehow 're-activated' their original viral infection, either by suppressing their immune system (through heavy drinking, opiate drugs, or immuno-suppressant drugs), and have actually 'relapsed.  This would be dependent on the research theories that demonstrate an ongoing sub-detectable very low level viral infection long term AFTER SVR has been achieved.  

On this board you will get lots of flak if you have an opinion that falls in line with this last group, or the 'viral persistence' camp.  Even though a large number of independent HCV and viral researchers have demonstrated this 'persistent virus' to be a verifiable phenomenon after SVR, many either dismiss their findings out of hand, or assume that their findings must be flawed.  To many out there, the fact that most Hepatologists call the treatment, and SVR a "CURE", then presumes that the virus must be completely eradicated and gone forever from all compartments in the body, and never can return.

This belief is still waiting for solid proof, one way of the other, and I think that only after more research, and also longer term studies following SVR's, and looking at any relapsers that develop, will we really get answers to these questions.  Either the virus is in a sort of 'quasi-permanent' remission, or it is totally gone forever, CURED so to speak, and there is honestly no real final answer yet.  Regardless of what either side claims on this forum, there is plenty of scientific ammunition to support either belief at this point, and nothing near a real consensus in the scientific community.  Time will tell.

DoubleDose

[jmjm530]

I didn't get the impression that "CO" was talking about viral persistence after SVR, an issue which I intentionally avoided per my first sentence second paragraph, last post.

Are you saying that you believe alcohol can "reactivate" Hepatitis C in an SVR? And I use reactivate in the sense of an SVR becoming HCV detectible using conventional PCR and TMA testing. My understanding is that is what "CO" is talking about, but I'm sure she will correct me if wrong.

[jmjm530]

I just read your post on the related alcohol thread and it leads me to believe that there are two different discussions going on here, since you appear to believe that light drinking  SVR is OK. Again, I think what CO is talking about is alcohol turning an SVR into someone HCV positive via conventional testing. I'm assuming you agree this is not possible but certainly won't speak for you.

[DoubleDose]

What I am saying is that CO's comments about remission, whether CO is aware of the 'persistence theory' or not, would necessarily be 'dependent' on this theory being valid, to take place.  If there is actually a 'viral remission' that occurs after SVR, then the assumption would have to be that it COULD be reactivated potentially.  Alcohol would be a likely cause for re-activation, if the 'remission' research and theory ends up being valid.

I am NO claiming that either belief is valid, since we do NOT have firm, final proof or consensus yet.  We have statements, we have opinions, etc.  But final, ultimate, agreed upon proof of either total eradication, or remission, is not here yet.  Unless you know of some meeting between the various camps of viral researchers where the differences have been ironed out and agreed upon?  

So, what I am saying, is that if CO's idea of remission is indeed an eventual reality, then their supposition that alcohol could possibly provoke a relapse, would not be an outlandish suggestion.  Especially in light of the studies on HCV rates in alcoholics, etc. that we have discussed at length in the past.  

We FIRST NEED a real consensus from the research and scientific community on the validity of either "total eradication, permanantly and forever', OR, "remission, based on some persistent viral mechanism, that is not well understood yet"

Note again, that I did not claim either opinion to be accurate or true.  We don't have enough information yet.

DoubleDose

[jmjm530]

OK, so you agree that's it's OK to drink lightly after SVR but you won't say that it realistically won't reactivate the virus? We're not talking about whether CO's comment is "outlandish" or not -- I never said that -- just that in the real world I haven't seen anything to suggest that one should modify one's drinking behavior (within the confines mentioned) because of HCV reactivation using the conventional definition which CO apparently does since she uses the phrase "become active again" which in common usage refers to what is commonly called "relapse" and nothing to do with the persistence theory. Not try to put you on the spot, just trying to clarify things for others in a discussion that is now starting to mix viral persistence theory with practical opinions re light alcohol use post tx.

What I'm saying -- and what I thought you said in another thread -- is that it's OK to drink alcohol post SVR within the limits mentioned. I believe that is the point that was being originally discussed and that many here may be interested in.

-- Jim

[DoubleDose]

Yes I am saying it is probably OK to drink in very light, infrequent, moderate amounts, after SVR, and NO I don't think that this sort of drinking could ever 'reactivate' a virus. IF it were in remission.  What I do think is this: if it turns out that HCV is actually 'in remission' after SVR, rather than absolutely eradicated and gone forever' , then I think that extremely heavy drinking, from everything that we know about the virus and alcohol abuse, would be a likely factor in potential viral 're-activation' , along with the other assumed culprits, like extreme immune system suppression.   There are still about 2% of long term SVR's that have demonstrated late 'relapse' or viral infection, well after the one year point of SVR.  Though a 'small' percentage, the cases are largely unexplained as to the EXACT and definite cause of relapse.

And, NO,  I disagree that remission has nothing to do with the 'viral persistence' research!!!  Quite the contrary.  I believe that the issue of 'remission' has EVERYTHING to do with persistent virus.  I would think that this extreme, low level, persisting virus, hiding wherever it might be, would be the actual 'resting place' for the virus in remission.  So maybe, the immune system somehow 'controls' the low level virus at some point, in SVR's, and holds it there permanently, in remission.  Whether this 'remission' could lead to a re-activation is still very cloudy, and controversial.  It would probably be extremely rare, but IF it can happen at all, ever, in just one case, then you have a situation of 'viral remission', and re-activation rather than total eradication.  Just not enough long term study and validation on either front currently.

Again Jim, the final answers have NOT been resolved yet, or agreed upon by the top scientific researchers.  You may believe that the answers are here now, firm and final.  But that does not in fact mean that this is the case.  I think that even HR leaves this door wide open in his past commentaries about viral persistence, and other forms of infection in cellular mediated tissues, etc.

I hope I am being clear, and that you do not misinterpret what I am claiming.  Because, I am saying that we just don't really have these answers yet.  I am not sure what you are claiming?

DoubleDose

[jmjm530]

DD: Yes I am saying it is probably OK to drink in very light, infrequent, moderate amounts, after SVR, and NO I don't think that this sort of drinking could ever 'reactivate' a virus. IF it were in remission.
--------------
That was the only issue I was discussing and thought the only issue "CO" was discussing. So we agree at least on the above point. The rest has been covered -- both sides -- extensively in other threads.

-- Jim

[DoubleDose]

Glad to see we are in agreement.

I don't think that CO is only referring to the sort of 'light drinking' that we discuss for SVR's though.  It looks to me fro the psot that her husband is moving toward more problematic drinking, more frequently and with more alcohol heavy drinks (hard liquor, etc.)  This could become a problem on several fronts.  First, even without the possibility of remission/reactivation, a cirrhotic drinking hard liquor, on an increasing basis could easily increase the odds of HCC dramatically.  This has happened MORE frequently in SVR's who were beyond stage 3.  The second issue that I see, is that if there is really a possibility of 'reactivation' of the virus, heading toward problem drinking, and hard alcohole use is not the best direction to be heading.  If the drinking spirals further into the 'heavy abuse' category, then 'reactivation' would be a 'concern' at least, if there is a true remission that takes place.  

If the drinking remains very light, and 'safe' to some extent, then he should be relatively OK.  We hope.  Again, the cirrhotic issue is central.

[mremeet]

Moderate to light amounts of alcohol consumption post SVR will not "reactivate" the virus (in the event the virus is even there at all). If it did, I never would have achieved and sustained my own SVR (along with a whol lotta other folks). Even heavy drinking will not "reactivate" the virus (again assuming it's even there). Also, the durability of SVR beyond 2 or 3 years is *extremely* reliable, and for all intensive and practical purposes constitutes an outright cure. The supposed "2%" of SVR's that DD refers to that "relapse" afterwards can very easily and reasonably be explained by (1) sampling/testing/experimental error, and (2) re-infection.

[HCA]

Drinking post SVR cannot possibly cause relapse morever patients who have had transplant post SVR ( and there are such examples) do not relapse in the face of the harsh immuno-suppressant drugs given to prevent rejection.RNA traces found in SVR patients (often tested post mortem) are weak quasi-species and are not thought to invade cells liver or otherwise.

[DoubleDose]

HCA:  This is news to me.  Weak quasi-species??? (Who has ever documented these?????)  Not thought to invade liver cells???  RNA traces????  Where did you get this information.  You are talking about something entirely different than the "persistent replicating virus" found in recent years by researchers in LIVE SVR's, years after finishing therapy.  And the two suspected cases of relapse, by the way, were both in patients who had received heavy doses of immuno-suppresant drugs, after SVR.  Both were suspected to be late relapses!

Mremeet  you said: " The supposed "2%" of SVR's that DD refers to that "relapse" afterwards can very easily and reasonably be explained by (1) sampling/testing/experimental error, and (2) re-infection."

Well, yes you can explain it that way, if you assume that to be the case.  These assumptions were never proven to be the case though.  Just a possible explanation.  Let's not confuse conjecture with proof.   If you want to just 'blow off' the 2% fine.  Don't call it science though!

DoubleDose

[alagirl]

I believe that I concur with Dr. Shiffman on this one:


http://www.news.vcu.edu/news.aspx?v=detail&nid=2096

For immediate release:
5/21/2007

Anne Buckley
VCU Communications and Public Relations

Current treatment for Hepatitis C can be considered a cure, VCU researcher announces
Disease is leading cause of cirrhosis, liver cancer and the need for transplants

Video Clip 1: "THIS LONG-TERM STUDY SHOWS THAT 99 PERCENT OF PATIENTS WERE CURED OF THE HEPATITIS C VIRUS."

The use of peginterferon alone, or in combination with ribavirin, points to a cure for hepatitis C, the leading cause of cirrhosis, liver cancer and the need for liver transplant, a Virginia Commonwealth University researcher said today.

Mitchell Shiffman, M.D., professor in the VCU School of Medicine, and chief of hepatology and medical director of the Liver Transplant Program at the Virginia Commonwealth University Medical Center, is one of the lead investigators in the study, which was presented at the 38th annual Digestive Disease Week conference in Washington, D.C. VCU was among about 40 sites worldwide studying pegylated interferon alfa-2a, manufactured by Roche Inc.

Nearly all — 99 percent – of patients with hepatitis C who were treated successfully with peginterferon alone, or in combination with ribavirin, had no detectable virus up to seven years later. Researchers say this data validates the use of the word "cure" when describing hepatitis C treatment as successful treatment is defined as having undetectable hepatitis C virus in the blood six months following treatment.

"We at VCU are encouraged by this data because it is rare in the treatment of life-threatening viral diseases that we can tell patients they may be cured," Shiffman said. "In hepatitis C today, we are able to help some patients achieve an outcome that effectively enables them to put their disease behind them."

[alagirl]

There are still about 2% of long term SVR's that have demonstrated late 'relapse' or viral infection, well after the one year point of SVR.  Though a 'small' percentage, the cases are largely unexplained as to the EXACT and definite cause of relapse.

and

"Again Jim, the final answers have NOT been resolved yet, or agreed upon by the top scientific researchers."
----------------------------------------------
The world population purportedly has a 3% hep c rate (I heard this on the radio the other day, don't know where they got the stats).  If that's true, I don't know why its so outlandish to believe that 2% of the folks who were SVR got reinfected.  And you know what else I think?  I think addiction is a very difficult thing and I think that there are some addicts who have hep c who use IV drugs off and on for years.  They may stay sober for years at a time, but then they fall of the wagon from time to time and start using drugs again.  There are TONS of fifty and sixty year old IV drug addicts in the county where I live, and many of them are treating hep c.  A LOT of them are treating at UAB.  It is certainly not beyond the scope of imagination that some of them have been in these studies during periods of sobriety and have then been reinfected.  And it would also seem to me to stand to reason that there would be more people of the same genotype in these population areas where a lot of IV users cluster.

So if some of these folks were in a study and then went back to their old ways, with their same friends, it wouldn't be a huge mystery that they came up with the same genotype again.

Also, if 3% is really the number of people with hep c in the world, then it's not that weird if one or two percent of the people who are SVR are somehow, on purpose, by accident, or by misadventure, infected again a few years later, particularly since many of the people on this board have no risk factors and don't know how they were infected.  

I think that re-infection makes more logical sense to me than this virus lurking in some strange place in my body that nobody can even really adequately explain to me.  If we had issues with people re-infecting themselves, HIV patients who were formerly SVR would be dropping like flies.  They have the worst immune systems around.

Who is it, and I'm asking because I honestly don't know, who hasn't resolved this question, which scientists?  And do they still feel that way in light of Virginia's research last year?  

[can-do-man]

Says.............So if some of these folks were in a study and then went backBack pain - low
Back strain treatment to their old ways, with their same friends, it wouldn't be a huge mystery that they came up with the same genotype again.

And..............I think that re-infection makes more logical sense to me than this virus lurking in some strange place in my body that nobody can even really adequately explain to me
-----------------------------------------------------------------------------------------------

You get my vote for the best answer....... Best to you girl

cando

[alagirl]

the type of therapy you describe with your father taking a lot of shots - but I didn't hear you say anything about pills with the shots - sounded to me like he might have been on interferon monotherapy.  

You said he cleared, but I was wondering if he went back and had his re-check at 1 year.  That 1 year re-check is pretty essential in making sure that you're really SVR.  After we finish treatment successfully, we kind of hold our breath a little until we get our 1 year clearance, and then we know we're good to go.  I'd make sure he goes back and asks for a viral load test, particularly if he didn't get that 1 year check.

IF he is clear, I wouldn't worry about the drinking reactivating his hep c virus.  The problem with your father is that he already has a lot of damage to his liver - from what you're telling us.  He definitely needs his enzymes checked and possibly some other testing per his doctor to see how much additional damage he has.  Additional alcohol can only hurt his liver more.  I'd take things one at a time though, and get the medical testing done (hopefully he'll agree to that) and then go from there.

[can-do-man]

Sorry, alagirls comment should have read..................So if some of these folks were in a study and then went back to their old ways, with their same friends, it wouldn't be a huge mystery that they came up with the same genotype again.

[mremeet]

"Well, yes you can explain it that way, if you assume that to be the case.  These assumptions were never proven to be the case though.  Just a possible explanation.  Let's not confuse conjecture with proof.   If you want to just 'blow off' the 2% fine.  Don't call it science though!"

I'm most certainly NOT just blowing off the "2%" you're referring to. Far from it, I'm taking it head on (as alagirl has above as well). And it's not me that needs to provide proof that the 1-2% are "relapsers", it's you that has to provide proof that they are relapsers (which of course you can't). That said, let me delve a little more into what I (and alagirl) said previously:

Let me start by asking you something DD - do you think there is *any* sampling or measurement error in the tracking data for long term SVR's? And by "tracking data" I mean the lab tests that define a patient as being UND. Are there ever false negatives? If so how often? I think we all believe that the tests for the most part are accurate, but obviously they can't be 100% accurate all of the time. Any reasonable, well informed and intelligent person with a basic knowledge of science and human fallibility knows that there is some error involved (as there ALWAYS is). Sometimes blood samples are mixed up or otherwise mishandled, leading to wrong results. And sometimes the blood sample is handled/processed properly, a correct result is obtained - but either the paperwork associated with those results is mishandled, or it is simply misinterpreted (as we see here all the time with arcane PCR test results). This "realm of error" is real. It exists, and that's an absolute fact. So there is no question whatsoever that at least some of the so called "relapsers" within that much taunted 1-2% are actually people who never cleared in the first place - they were misidentified as SVR's due to testing/reporting error. So the only question that remains, is how many of these people exist? What percentage of the 1-2% do they constitute? Is it 1/2%? Maybe 1%? Maybe 1.5%? What's a reasonable number? Why don't you tell me DD. Or are you of the opinion that there is ZERO experimental error?

We can also turn this scenario on its head for a bit more clarity. Lets assume for a moment that successfully treating and achieving SVR really does mean total and complete eradication (putting the persistence stuff aside for the moment). Lets assume if you treated and achieved SVR, then that's it, the virus is gone for good; it is TRULY eradicated. Now, lets assume these people are tracked in the exact same manner as they are now. Are you under the impression that even though we know that there is total eradication that we won't see some residual data that identifies some people as "relapsing?" Or do you think that the sampling process is absolutely bulletproof, completely and totally without error? If not, what's a reasonable margin of error? You tell me...

Also, I think it’s important to realize that there’s a small group of people that do NOT achieve SVR after finishing treatment, and yet they SVR anyway. By that I mean they finish treatment, they test UND initially, and then a PCR comes back saying they’re HCV+ again. But the initial test results were erroneous, they’re really not HCV+, they’re really UND. They’re really SVR, but they’ve been misidentified as relapsers. They’re similar to the group described above except they’re the inverse of that group. Unfortunately to my knowledge there isn’t a statistical database indicating how often this happens, but I’ve heard it estimated by knowledgeable doctors that the testing error rate is about 1%, maybe 2%. Strangely similar to the so called “relapse” rate of SVR’s huh? I’d be willing to bet that the people described in this paragraph constitute about 1-2% of “failed tx’ers”, or people who were initially misidentified as having failed treatment, when in fact they really had achieved SVR. (and in fact I’ve seen a few folks like that here on this forum over the years)

The second issue is a very obvious one, that being reinfection (as alagirl has precisely hit on the head in her post). First let's start with the plain fact that about HALF the people who have (or had) HCV got it through IV drug use. And although many of the people who were once IV drug users successfully stopped using many years ago, many more are current or recent users (especially amongst the younger set). And the recidivism rate amongst those current users is quite high. It's very common for active users to go on and off heroin or coke or whatever they choose to inject in their arms (especially for heroin) for years and years (often until their death). So there's a not insignificant number of people amongst the SVR group that were (1) infected by IV drug use initially, and (2) will start using again at some in time after achieving SVR. And because of the very onerous and negative social stigma associated with IV drug use (something I've experienced myself in doctor's offices many times, and I'm not even an IV drug user), an IV drug user is not very likely to openly admit to using drugs again, especially after achieving SVR. This is especially true within the context of the authority figures (doctors and hospital personnel) the IV drug user must honestly disclose this information to. An IV drug user may also deny using because he/she may fear being denied healthcare in the event they disclose they were reinfected. There is no motivation for an IV drug user to admit to authority figures that they’ve re-engaged drugs, and there are reasonable/logical motivations for denying as much.

cont...

[mremeet]

(cont...) So clearly, there IS drug induced reinfection that goes unreported. There is often no way for doctors and medical personnel to know if a person is lying if they deny IV drug use. All they can do is record what they are being told by the patient. And if they have a former SVR in front of them that says he's not using, then that person would simply go back on the books as a "relapse." The only question is how many of these people exist and what percentage do they constitute in the 1-2%? So once again, you tell me DD: Do you acknowledge that these people exist? And if you do, what percentage do they constitute within the total of "relapsers?" 1/2%? 1%? 1.5%? Remembering the large percentage of people who were infected via IV drug use in the first place, and the rate of drug relapse amongst junkies - you tell me DD, what's a reasonable number?

Lastly, there's the equally obvious scenario that if you're living and moving and rubbing elbows amongst your fellow people out in the general population, you might just pick up HCV again given enough time. That's how every single one of us got HCV in the first place! We were in the wrong place at the wrong time – every…single…one of us. Achieving SVR does not physiologically immunize us against being reinfected. It also does not immunize us from the myriad of possible infection routes (many of which are not clearly known) that have nothing to do with IV drug use. And some of us may also engage in seemingly innocuous behaviors that in fact expose us to significant risk (especially in repetitious exposure scenarios). The lady that regularly has her nails done at the salon that reuses bloody, unsterilized utensils. The guy that goes to the barber that uses the same unsterilized straight razor on all of his customers. The woman who gets a new tattoo every 6 months from a friend who's "really good at it." There are countless other "mysterious scenarios" that you will never know you're being exposed to, but in fact YOU ARE. That's the chance we all take living amongst one another, and it doesn't go away just because you were successfully treated for HCV. And these people aren't aware of their exposure risk, so when they're queried by their doctors as to how they may have gotten reinfected, they simply honestly shrug their shoulders. The doctor can only record “no known reinfection” which is then later interpreted by someone like you as "relapse." So one more time, you tell me DD: Do you acknowledge that these people exist? And if you do, what percentage do they constitute within the total population of "relapsers?" 1/2%? 1%? 1.5%? You tell me DD, what's a reasonable number?

And DD, once you add all of what you perceive as reasonable numbers from the various subgroups described above, what do you come up with? Did you make it to 1%? Maybe 2%? Like I said in my original post: "The supposed "2%" of SVR's that DD refers to that "relapse" afterwards can very easily and reasonably be explained by (1) sampling/testing/experimental error, and (2) re-infection."

[mikesimon]

Immune suppression leading to hepatitis C virus re-emergence after sustained virological response. August 2008

Department of Medicine, Division of Gastroenterology-Hepatology, Weill Cornell University Medical College, New York, New York. July 2008

Sustained virological response SVR is defined as undetectable HCV RNA in plasma 6
months after therapy has been discontinued. Relapse or re-emergence of viremia after SVR is rare. We report two patients that relapsed when immune suppressive therapy was given within a few weeks of achieving SVR. Patient 1 received prednisone for bronchitis and patient 2 relapsed soon after immune suppression was started post renal transplantation. These data suggest that the early phase of SVR might be associated with incomplete protective immunity. They suggest that sterilizing immunity with complete elimination of virus is unlikely. The cases also caution against the use of immune suppressive therapy in the immediate aftermath of SVR. J. Med. Virol. 80:1720-1722, 2008. (c) 2008 Wiley-Liss, Inc.

PMID: 18712814 [PubMed - as supplied by publisher]


Recurrence of HCV Infection in a Sustained Responder After Chemotherapy for Non-Hodgkin's Lymphoma: Successful Retreatment. July 2008

It is known that sustained virological response (SVR) in patients with chronic hepatitis C is associated with sustained elimination of hepatitis C virus (HCV) and that late relapse after SVR in HCV patients is doubtful. A 47-year-old man with chronic hepatitis C genotype 3, achieved SVR after combination treatment with pegylated interferon and ribavirine for 6 months. Sixteen months later non-Hodgkin's lymphoma was diagnosed. After successful completion of chemotherapy for non-Hodgkin's lymphoma, he presented with HCV infection recurrence of the same genotype. Retreatment with the same schedule resulted in normalization of aminotransferases and disappearance of HCVRNA from the serum. This case suggests that recurrence of HCV infection in a sustained responder may be probable after immunosuppressive therapy. Prevention is currently impossible but retreatment may be successful.

PMID: 18626242 [PubMed - as supplied by publisher

[DoubleDose]

mremeet:  Wow!  You spent a lot of time to say thet the 2% are probably reinfected, or testing errors.  Again, this has just not been proven.  You can't say who was a true relapser, or a reinfection or testing error.  Thanks for the novel (above).that says the same thing for twenty minutes.  I am not going to argue any further, since the answers about the (roughly) 2% relapsers are not able to be verified.  

And, alagirl, here is the criterion that Dr. Shiffman used for employing the term 'cure'
As taken from your above post:

"Researchers say this data validates the use of the word "cure" when describing hepatitis C treatment as successful treatment is defined as having undetectable hepatitis C virus in the blood six months following treatment."

They DO NOT say that the virus is totally eradicated, or that the virus does not possibly exist in a latent or persistent state, but they only say that the viral load in the blood is undetectable after six months, and remains so up to seven years later.  I agree with all of this by the way, and I also call it a 'cure', but this does NOT contradict the existence of low level persistent virus (see all the research articles under TnHepGuys Occult page), nor does this definition say that the virus could NEVER, EVER return, or be reactivated in some very small percentage of those 'cured', under some extreme circumstance.  Until they really can accurately detail the exact reason for each suspected late relapse, they cannot validate or disprove the concept of a true relapse.

They are defining 'cure' as keeping the virus undetectable in the blood for up to seven years.  I also use this definition for 'cure', and enjoy my own SVR everyday on that level.  I do NOT think, though, that I have been proven to have absolutely eradicated all viral replicating copies anywhere in my body.  It may be true, but research keeps showing otherwise.  If you have a problem with that, speak to the many 'persistent HCV', and Occult HCV researchers, not to me.  I didn't run the amplification studies.

An analogy is Chicken Pox....and you may have had it, and been 'cured'...not to have it again for twenty, thirty, or forty years. . But some people DO get it again, as a REACTIVATED virus, decades later, in the form of Shingles.  A prominent HCV doctor did concede to me two years ago that this is a possible scenario for HCV, but that it was a moot point, since almost all SVR's stay undetectable.  I would never use his name, and I doubt he would say this in public, but he DID concede this was a possibility in a meeting that I had with him.

I really don't care much one way or the other, but I would like to find out for sure, if the virus remains in any way, and if this is really remission (on a permanent basis) or a total eradication of the virus.  The definition that Shiffman used allows for the 'remission' scenarion, in that it only states that the virus remains undetectable over long periods of time.  Get the difference in nuance?

DoubleDose

[nygirl7]

"Patient 1 received prednisone for bronchitis and patient "


It does go to reiterate how dangerous prednisone really can be - it's one of those meds that you'd better hope your doc knows about, we've seen that before even in here people having breakthrough while getting it.

Scary when you wonder how many doctors might not know that info. I mean I've taken it several times in my life and wouldn't have known if not for this forum that there was any reason not to take it at all.

[TnHepGuy_]

Thanks for posting those two new articles.

I just added them to the 'Occult Hep C Health Page' - http://www.medhelp.org/health_pages/Hepatitis/Occult-Hepatitis-C/show/54?cid=64


TnHepGuy

[DoubleDose]

Assuming you can still objectively read and process information, I would advise that you read the two recent reports posted above by mikesimon.  I don't think any further comment is necessary.  

DoubleDose

[mremeet]

I did read them. It's the usual extremely rare, anecdotal, one off story of some poor sap who (1) was recently (or very recently) "SVR", (2) got cancer or a transplant etc, required (3) massive immunosuppressive therapy (or had undergone immunosuppressive therapy before and/or during and/or immediately after treatment). It's the rarest of the rare, it's almost always under the most extreme circumstances imaginable, almost always associated with massive immunosuppresion therapy and extreme extenuating complications, and it's almost always someone who has a "fresh" SVR instead of someone with a more fully established SVR that has been proven with years of negativity (clouding the issue if the patient had truly cleared the virus as demonstrated by years of sensitive, low level PCR negativity). And they provide no information on possibility of reinfection or other pertinent details that may help establish likelihood of reinfection or possible initial testing error (which again are possibilities). Guys like this would constitute probably less than 1/100th (or even 1/1000th) of 1 percent amongst the 1-2% of "relapsers" that we were discussing earlier. In short, it's called not seeing the forest through the trees.

But no worries, it's duly noted that you wont answer the questions above. It's an absolute fact that some of the 1-2% "relapsers" are reinfections. It's also an absolute fact that there is experimental sampling error that both misidentifies a certain number as being SVR in the first place (when they're not) AND misidentifies a certain number of SVR's as having relapsed, when in fact they haven't. Those are irrefutable facts. It is not conjecture, it is not speculation, it is not some fanciful tale. It is not a matter of IF on either subject, it's simply a matter of HOW MUCH.

In the meantime, enjoy re-reading your post last time we discussed this two years ago where you didn''t answer the same questions then either. Why won't you answer the questions? What are you so afraid of? I already know the answer to that particular question, so you needn't respond to it. But considering your keen interest and breadth of knowledge on this particular subject matter, and in the spirit of open communication and scientific discourse, it'd be nice to see you respond to them. I won't hold breath though, just like I didn't almost two years ago. ;-)

http://www.medhelp.org/posts/show/95474?post_id=post_742775

[DoubleDose]

I was just hoping you WOULD hold your breath!  Now that would be news!

What you wrote above is really squirming and wriggling to the extreme. Yea I know, every immuno-suppression case that causes a relapse is a 'special' case to you!  Hey, no kidding!  I said relapse would be a RARE situation, but is possible!  Because the virus MAY just be in remission.  That's what the doctors plainly state in the above referenced article.

And your 'absolute fact' above regarding reinfection and lab error has yet to be supported by any study that I have seen.  The fact is that the majority of the relapse cases are not yet unequivocally explained, only a small percentage of them have been proven reinfection, or lab error cases.  Where is your data on the 2% relapsers?  Other than supposition or logic would have you believe...etc.  I, on the other hand, am NOT claiming how many or which ones are true relapsers.  Only asking for follow up and real answers on those who have relapsed.  

Waiting for the Barrage...DD

[mremeet]

Once again you WILL NOT answer the questions. What's that all about? Why are you so evasive? Why are you so fearful of "THE QUESTIONS?" They wont bite you big guy, they're merely questions. Just words written in the form of a query, that's all.

As far as "Yea I know, every immuno-suppression case that causes a relapse is a 'special' case to you!" Yeah it is a special case to me. It's a special case for two reasons: (1) because it's extremely rare (with an emphasis on rare) which by definition makes it a special case to *everyone* (i.e. not just me), and (2) because I myself underwent extensive immunosuppressive therapy smack dab in the early phase of MY OWN treatment! (including IV steroids and gobs of prednisone) And I was tested with a sensitive PCR all during my extensive immunosuppressive fiasco, and never ONCE did I become detectable again, and went on to SVR fine later. So yeah, I actually have personal first hand experience with that particular scenario, and not only do I have experience with extensive immunosuppression, I actually have it long *before* SVR-ing, actually DURING treatment. I'd say that qualifies me to weigh in on the matter, certainly as much as you or anyone else (or are you suggesting my anecdote is any less valid than the ones Mike Simon provided above??). But again yeah, those one off, rarefied anecdotes of "I just got my SVR, I have special/extreme problems which confound the validity of my SVR, and now I'm on bolus steroids, and oops!! I gotta measurable VL now!" stories that you and mike simon are so fond of (and mike simon used to mistakenly claim to be one himself) *are* special. They're very special, just like you. ;-)

[DoubleDose]

The stories are documented from doctors and researchers, not anecdotal stuff as YOU are discussing.  You were taking interferon along with immuno-suppressants, and not suprisingly remained undetected during tx.  We are discussing SVR's, and post tx relapse, and in rare cases a return of the virus in several documented cases.  You drifted off on us!  

By the way, do you have a need to argue?  I am wondering why you have such difficulty dealing with open questions, and issues that are still unresolved.  You seem to get pretty worked up, and have a one track slant on everything.  I just don't buy your approach.  Sorry.

[comeagain]

Artesian I can´t provide any study about the overwhelming risks about drinking alcohol when cirrhotic but that is what I`ve always heard.

I´m sure both mremeet and Double Douse or some other very knowledgeable person on this forum can provide you with that and also explain the proces of a cirrhotic liver and how very urgent it is for a person as your father to live a very nontoxic and healthy lifestile.

And I dare say that there is no risk to get the HCV back unless he get so pissed that he dont know what his doing and end up with a needle in his arm, and that he maybe not even remember afterwords.

God bless to you and your entire family

ca

[mremeet]

If you don't know what the definition of "anecdote" is (which you obviously do not), then look it up. Because the studies that MS posted are anecdotes, they are not highly controlled scientific studies involving large numbers of people. My own personal anecdote is no less valid, assuming you trust that the information I'm providing (and my healthcare team) is accurate.

And in true form, you (and MS) are throwing out a red herring with the relapse anecdotes in an attempt to deflect attention away from the subject at hand. We weren't originally talking about relapse anecdotes, we weren't even talking about the viral persistence theory. We were only talking about what likely constitutes the bulk of the 1-2% of "relapsers" out of the 98-99% SVR rate that you referenced. The extremely rare anecdotes that MS listed (and you "red herringly" refer to) most certainly do not constitute that 1-2%, no where even remotely near that. Myself and alagirl responded with detailed and explicit posts thoroughly describing a very obvious chunk of who the 1-2% really are. You wont respond to those facts because they don’t fit into your preconceived notions, and they erode the confidence in your coveted "relapses." And as discussed earlier, your motivation for needing the persistence stuff to be true is because it bolsters and validates the irrational fear that you are continually infected and are passing along the virus and its symptomology to your friends and family. Without viral persistence being real, you're back at square one trying to explain the irrational fears you have. In other words, you're confronted with the psychology of the matter instead of the physiology of the matter. You're confronted with the notion that it's all in your head, and that you really aren't passing the virus or its symptoms on to anyone else. Obviously for you, that's worse than for viral persistence to actually be true, incredibly.

So just like the other stuff we've discussed earlier, anything that doesn't fit has to go (or is simply ignored). And if anything has been brought up that cuts right to the bone that you can't respond to in a direct and straightforward manner, it needs a red herring so that the channel can be changed. That red herring this time is extreme relapse anecdotes, followed up by an ad hom or two to personalize the matter. Well, rest assured you can throw out a veritable fish market of red herrings, ad homs and straw men, but it won't change the facts surrounding this issue. In the meantime, I think you'll find these links helpful ;-)

http://www.youtube.com/watch?v=w6ylxWcwkUM

http://www.youtube.com/watch?v=JXlXN84NiEI

[HCA]

The assertions in my earlier post were relayed to me in conversation with two Professors of Medicine both specialising in viral hepatitis.Probably the leading specialists here in the U.K.I shall not name names  but were I to do so you would find many articles on Google scholar on hepatic virology.I had specifically asked about the issues I commented upon.

[DoubleDose]

Yes indeed, I did read that you and alagirl made the case for relapsers all being either reinfections or lab testing errors.  I did not see the studies backing up and confirming both of your opinions.  All I saw was two people making a claim that the reason for all relapse cases must absolutely be one of the two situations described above.  Is this what you call proof?

Pointing out a few rare cases of relapse, as you describe myself and mikesimon as doing, is not at all off-base in my opinion.  If TRUE relapses can be documented at all, in any real SVR's, even just one, then I think that the exception may indeed prove the rule.  Why does immuno-suppression sometimes cause the virus to return?  Did you have an answer for the doctors and researchers?  We should get you their e-mail address.  They will be anxiously awaiting your explanations!

By the way, I am the one with questions and the open mind.  You are the one with all the answers, it seems.  So please stop with constantly asking me to give you answers, to questions that have not been fully answered yet.  You are the guy that wants to prematurely put a lid on everything, and call the game 'over'.  

That's your right by the way, just don't expect all of us to cow-tow to your line of reasoning...especially with no answers to the large body of research that contradicts your conclusions.  You end up throwing out heated 'opinions' and calling them facts.

Note the quotes from the cases reported by the doctors above:

"This case suggests that recurrence of HCV infection in a sustained responder may be probable after immunosuppressive therapy. Prevention is currently impossible but retreatment may be successful. "   THEY said that, not ME!!!  Did you catch the 'probable'???       and:

"They suggest that sterilizing immunity with complete elimination of virus is unlikely. The cases also caution against the use of immune suppressive therapy in the immediate aftermath of SVR. J. Med. Virol. 80:1720-1722, 2008. (c) 2008 Wiley-Liss, Inc. "   Did you catch the 'unlikely'????   They said it!!!  Go scream at them!!

Again, their commentary.  By claiming that my suggestions are absurd, you also are  claiming the medical researchers to also be out in left field.  With no supporting data of your own, of course.  Hey, that's your right.  Opinions are like....Oh well, you know the limerick.

DD







DD

[willing]

mremeet:
the  most effective, and in fact the only credible, way of promoting the 'complete eradication' hypothesis would be to extend TN's list of publications with further  evidence  that supports it

all:
here's a more extensive quote from the close of the Lin'08 paper  Mike posted. Note the last sentence suggests both sides of the argument may be right in the long run, though the case report of the relapse 8-years post SVR suggests it may a pretty long run.

"Viremia can be maintained at clinically undetectable
levels either protective or sterilizing immunity. In both
humans and chimpanzees, natural resolution of acute
HCV infection is associated with the development of
protective immunity. This is characterized by mild,
short-lived infection on re-challenge [Bassett et al.,
2001; Mehta et al., 2002; Nascimbeni et al., 2003;
Lanford et al., 2004]. Protective immunity can be
overcome by immune suppression, well illustrated in
an IVDU that had previously cleared HCV, but
developed persistent chronicHCVinfection after becoming
HIV-1 positive [Mehta et al., 2002]. Sterilizing
immunity on the other hand is associated with complete
eradication of virus and therefore does not relapse with
immune suppression. Reports that HIV-1 infection can
lead to relapse after resolution from HCV infection
[Mehta et al., 2002] is reminiscent of our two patients,
both of whom relapsed after immune suppressive
therapy. The report of HCV relapse several years after
SVR, in relation to corticosteroid therapy [Lee et al.,
2005] is also consistent with protective immunity as the
basis of SVR.

Protective immunity implies low levels of persistent
HCV replication, undetectable by current conventional
methods. Ultra sensitive techniques for determining the
presence of HCV RNA using a highly sensitive reverse
transcription (RT)-polymerase chain reaction-nucleic
acid hybridization (RT-PCR-NAH) assay, detected
HCV RNA in macrophages, lymphocytes or sera in the
majority of patients with SVR [Radkowski et al., 2005].
Virological relapse in our two patients may have been
the result of re-infection. However, disease recurrence
was associated with the identical genotype in both cases;
high risk behavior or exposure to ICV was remote in
patient 1; and donor kidney was HCV negative in
patient 2. A probable hypothesis might be that aviremia
in the immediate post treatment phase is maintained by
protective immunity and that sterilizing immunity may
follow as the small numbers of infected target cells are
eliminated."

[FlGuy]

Change a few nouns here and there and the discussion topic could be Global Warming.

[DoubleDose]

Willing:  Thanks for the additional input !  Fact based article with well founded conclusions.  Always good to hear from you, and see some specific literature that addresses the question at hand.  That's what I like...real data.  

Mremeet: Above is another medical documentation for you to throw rocks at.  The Occult site is just a click away,  in case you might have some research that you would like to post to support your assertions.  As for me, I'm going to sleep.  I'm tired of dealing with blather.

DD

[willing]

and no real polar bears were harmed in this thread

[DoubleDose]

Sorry that the answer to your original question for this thread has devolved into a very muddled discussion regarding the validity of 'relapse' for those with an SVR.  As you can see, there is not a consensus  of opinion(to put it mildly) on this issue, in the lay community, or in the medical and research community.  Understanding the mechanisms and behaviors of this virus is still a 'work in progress' no matter what anyone tells you.  Continuing research will help clarify many of these cloudy issues over time.  In the mean time, read both sides, and draw your own conclusions.  Err on the side of caution.

DoubleDose

[CoWriter]

"On this board you will get lots of flak if you have an opinion that falls in line with this last group, or the 'viral persistence' camp."


So I will be joining the unpopular group since I believe in viral persistence and the possibility of reactivation in special circumstances of immune suppression.  

Many studies have shown that.....

"It is possible that viral persistence and, specifically, the presence of HCV RNA in PBMCs may lead to HCV reactivation under special circumstances, such as immunosuppression."

http://www.ncbi.nlm.nih.gov/pubmed/18594984?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum



Here's a case about somebody who had been SVR for 8.5 years and the virus returned when she used immunosuppressants.  And it was proven that THE VIRUS WAS THE SAME and NOT RE-INFECTION.


Reemergence of Hepatitis C Virus after 8.5 Years in a Patient with Hypogammaglobulinemia: Evidence for an Occult Viral Reservoir.
  
"The testing of frozen serum from previous episodes of hepatitis CONFIRMED that the RECURRENCE of infection WAS FROM THE SAME VIRUS."

"That the phenomenon did not represent reinfection was proved by the fact that only a single amino acid difference in the NS5A region was found over the 8.5-year period. We interpret the minimal shift in quasispecies diversity and the repeatedly negative serum HCV RNA PCR assays to represent a low level of viral replication during this long quiescent period. Although considered to be a sustained viral responder, our patient continued to have a reservoir of low-replicating virus that was held in check but not eradicated by her immune system until the corticosteroid-induced immune suppression led to the relapse. Recent studies in immunocompetent patients support the presence of such a reservoir. An HCV reservoir that requires continued innate or T cell immune surveillance to prevent disease activity even years after the infection appeared to have resolved may exist in at least some sustained viral responders."

http://www.natap.org/2005/HCV/090505_13.htm



So viral persistence is a possibility and alcohol STIMULATES VIRAL REPLICATION and it's an immune-suppressant.  I don't believe that small amounts of alcohol will reactivate the virus but that was not the case being discussed on this thread.  artesian said his father was drinking daily and using hard liquor.

Thank you both for the great discussion.


Journal of Viral Hepatitis.  Sept 2007

Additive effect of ethanol and HCV subgenomic replicon expression on COX-2 protein levels and activity

Summary. The mechanisms by which alcohol exacerbates liver injury in patients with hepatitis C are unknown. We used the hepatitis C virus (HCV) subgenomic replicon cell system to evaluate the effect of ethanol on HCV replication and viral protein synthesis. Our results demonstrate that alcohol stimulates HCV replicon expression at both HCV-RNA and protein levels. Furthermore, we observed that ethanol treatment showed an additive effect in cyclooxygenase-2 (COX-2) protein expression and activity already induced by HCV viral proteins, and in turn increased HCV viral expression. Our results suggest that COX-2 activity is involved in ethanol-induced HCV-RNA and NS5A protein expression, because acetylsalicylic acid (ASA), a COX-1/2 inhibitor, blocked this induction and downregulated COX-2 protein expression and activity. Therefore, we suggest that ETHANOL INCREASES HCV REPLICATION, at least in part, by upregulating a key cellular regulator of oxidative stress pathway known as COX-2 or its products.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2893.2006.00837.x

[CoWriter]

"I don't think that CO is only referring to the sort of 'light drinking' that we discuss for SVR's though.  It looks to me from the post that her husband is moving toward more problematic drinking, more frequently and with more alcohol heavy drinks (hard liquor, etc.)"

MY husband?  LOL....that's how rumors get started, you know....LOL

[jmjm530]

DD: "On this board you will get lots of flak if you have an opinion that falls in line with this last group, or the 'viral persistence' camp."

CO: So I will be joining the unpopular group since I believe in viral persistence and the possibility of reactivation in special circumstances of immune suppression.
----------------
It's funny that it's "flak" if someone disagrees with you on this topic, but opinion if they agree. Did you think you received any flak in this thread? All I saw was a difference of opinion.

--Jim

[DoubleDose]

CO:  Sorry, I meant to say artesan, who started the thread, and Dad rather than husband.  My mind was getting blurry with all the long volleys that were taking place.  By the way, thanks for the quotes from literature above.  I think that the one case especially, really makes a pretty airtight statement that relapse after true SVR CAN occur in some circumstances.  I do believe this has been documented and accepted by most of the HCV medical community.

jmjm:   I hear what you are saying...BUT....if YOU were dealing with some of the long-winded, accusatory, and repetitive posts (as above), I think you might call it 'flak' as well.  I think that many of our members express 'opinions', in a thoughtful, and respectful way.  When people start calling me paranoid, and use derogatory terms in their purely subjective, unsupported  and argumentative ramblings, yes, I call that 'flak'.  I could call it worse but I am too polite.  I'm just the gentleman, Jim!  No seriously, I am able to respond to the differences of opinion that you and I have without feeling that I am being subjected to torture, and also with several other forum members.

  Its only a few that seem to latch on to a subject like a pit bull, and ignore all the data that is placed in front of them.  When the insults start to fly, I now throw them right back (where I used to just leave the thread).  Maybe its sometimes inflammatory, but I really feel that one good turn deserves another.  Maybe I am becoming too blunt or outspoken, but hopefully in the future I will be able to more effectively emulate Gentleman Jim.  

DoubleDose

[TnHepGuy_]

Thanks for posting the paper on PBMC infection. I've just added it to the 'Occult Hepatitis C' Health Page - http://www.medhelp.org/health_pages/Hepatitis/Occult-Hepatitis-C/show/54?cid=64


TnHepGuy

[willing]

thanks for the new study.. the plot thickens:

1) Gallegos'08, like Pham and Radkowski, but unlike the two recent French and the Bernandin paper, applied mitogen stimulation to the collected PBMCs before running the PCR. The trend is increasingly clear : every researcher that applies mitogen has found post-SVR RNA in PBMCs and every one that has not has failed to do so. Excerpt of the pre-PCR protocol from the methods section:

"Blood samples were collected 6–56 months (mean, 22 months) after the end of treatment in all patients. Additionally, 13 of the 25 patients underwent a second collection 13–49 months after EOT (mean, 28 months).

PBMCs from 10 ml of blood were isolated following centrifugation over a density gradient (Ficoll-Hypaque, Pharmacia, Kalamazoo, MI) and were immediately subjected to culture under mitogen and cytokine stimulation using variations of recently described methods [19]. In brief, PBMCs were placed in 2 ml of RPMI 1640 medium (Gibco BRL, Grand Island, NY) and 10% fetal bovine serum in six-well plates with the following combinations of mitogens and cytokines: (a) phitohemaglutinin (PHA, EY Laboratories Inc., San Mateo, CA) 5 μg/ml and interleukin-2 (IL-2, Roche Diagnostics, Indianapolis, IN) 20 U/ml; (b) PHA 5 μg/ml, pokeweed (PWD, EY Laboratories Inc., San Mateo, CA) 5 μg/ml, IL-2 20 U/ml, and IL-4 (Roche Diagnostics, Indianapolis, IN) 1 ng/ml. PBMCs were incubated at 37°C for 48 h. After culture, the PBMCs were centrifuged at 400g, re-suspended in 750 μl of TRIzol LS (Invitrogen, Carlsbad, CA) and stored at −80°C until analysis. Two 500-μl aliquots of plasma obtained at the time of PBMC isolation were stored at −80°C until analysis.

RNA was extracted from plasma and cells following a modified guanidium thiocyanate–phenol/chloroform technique using commercially available kit (TRIzol LS). The RNA extracted from 500 μl of plasma was used in a single nested reverse-transcriptase polymerase chain reaction (PCR) using a previously described procedure for the 5′UTR region [20]. RNA extracted from cultured PBMCs was diluted in 10 μl of DNase and RNase-free water, and stored at −20°C until analysis by PCR. "

I suppose we won't have a definitive answer until the same lab runs side by side with/with-out mitogen analyses, but my hunch is that the French/Bernandin protocols were deficient.

2) The detection rate found here was much lower, around 20% than what had been reported by Pham and Radkowski. Both of the latter only had access to SVRs from 'dated' tx : Pham used spontaneous and unpeg-IFN whereas Radkowski used SVRs from a RBV + unpegIFN. The patients used for this study SVR'd off current pegIFN+RBV  

The surprising implication seems to be that not all SVRs are created equal. If in fact the hypothesis at the end of Lin'08 is true, it may take years post-SVR for all infected cells to die off, and a stronger tx would leave the patient with a smaller guerilla war to be fought with the endogenous ifn.

"Currently, sustained viral response has been equated to the “cure” of the HCV infection, as it undoubtedly produces long-term clinical, biochemical, and histological benefits. But it is also clear that, after long-term follow-up of subjects with sustained viral response, up to 8% of cases will relapse [22]. The relevance of persistent HCV RNA in tissue, serum, or blood cells is not yet apparent, but it is plausible that it could be the source of HCV recurrence under special circumstances, such as immunosuppression. Support for this view has been recently provided by a well documented case in which a patient with IgG deficiency developed acute hepatitis C that responded to interferon therapy [23]. The patient was followed for several years, having persistently normal aminotransferase levels and the absence of serum HCV RNA by PCR assays repeated at least four times during her follow-up. Nine years later, the patient developed acute hepatitis. Six months before this episode of hepatitis, the patient had been receiving intravenous methylprednisolone with each IVIG infusion, and had also undergone several courses of prednisone for asthmatic episodes. Her aminotransferase levels were elevated greater than 15-fold and serum HCV RNA was detected. Corticosteroids were discontinued and, after 2 months, the patient’s liver function tests normalized and HCV RNA became undetectable once more. The testing of frozen serum from previous episodes of hepatitis confirmed that the recurrence of infection was from the same virus. This clearly suggests that HCV persistence, after therapy or natural resolution, might have clinical implications, especially in patients subjected to immunosuppression. This could certainly be of concern in liver transplant candidates who have received successful antiviral therapy in the pre-transplant period.

In conclusion, our results suggest that, in some patients with chronic hepatitis C, HCV RNA may persist in the PBMCs for up to 35 months after fulfilling SVR criteria following combined antiviral therapy with peginterferon alfa-2a and ribavirin. RNA persistence in PBMCs and sera was less frequent among our patients than that reported among those treated with standard interferon and ribavirin. At present, the clinical relevance of this finding is unclear. It is possible that viral persistence and, specifically, the presence of PBMC HCV RNA may lead to HCV reactivation. Conversely, it may also provide a low level of antigen exposure to keep the immune status that would prevent the reactivation phenomenon. "

[CoWriter]

"The surprising implication seems to be that not all SVRs are created equal. If in fact the hypothesis at the end of Lin'08 is true, it may take years post-SVR for all infected cells to die off,"



Late disappearance of hepatitis C virus RNA from peripheral blood mononuclear cells in patients with chronic hepatitis C in sustained response after alpha-interferon therapy.

García-Bengoechea M, Basaras M, Barrio J, Arrese E, Montalvo II, Arenas JI, Cisterna R.
Gastroenterology Unit, Hospital Arantzazu, San Sebastian, Spain.

OBJECTIVE: We aimed to investigate the modifications of HCV RNA (genomic and antigenomic strands) in peripheral blood mononuclear cells (PBMCs) of long-term responder patients to alpha-interferon therapy, and their usefulness as criteria of definitive HCV eradication. METHODS: We studied 10 patients with chronic hepatitis C with > 1 yr of sustained response after alpha-interferon therapy (normal alanine aminotransferase [ALT] and negative serum HCV RNA). Serum HCV RNA and genotyping were determined. Approximately 2 and 4 yr after completion of treatment we investigated the presence of HCV RNA (genomic and antigenomic strands) in PBMCs. Eight of 10 patients were rebiopsed 2 yr after discontinuation of treatment. RESULTS: The mean follow-up was 46.6 +/- 4.6 months (range, 39-51 months). In this period, all patients remained in sustained response. In the first determination, all patients had HCV RNA genomic strands and two patients had antigenomic strands detectable in PBMCs. Two years later only two patients had genomic and none had antigenomic strands detectable. After 4 yr of sustained response, eight of 10 patients lost HCV RNA from PBMCs. CONCLUSIONS: In the long-term follow-up, the majority of patients with chronic hepatitis C with sustained response after alpha-interferon therapy progressively lost HCV RNA from PBMCs. This determination in PBMCs is not a predictor of response.

PMID: 10406257 [PubMed - indexed for MEDLINE]

[CoWriter]

"Did you think you received any flak in this thread?"

LOL....not yet.

[jmjm530]

And chances are you will not, because on the whole your posts are respectful and deal with the topic at hand and not with characterizations of other people's posts. Once that begins than so does *** for tat.

[jmjm530]

hmmm I guess T*i*t (remove the asteriks) is a bad word with the software :)

[mikesimon]

As you know I test monthly with Heptimax. I think my transplant clinic does this for precisely the reason that is being discussed here - the possibility of reactivation in SVRs under immunosuppression.
Mike

[CoWriter]

Here's a few more that are not on your list.....


June 1994   Testing for hepatitis C virus sequences in peripheral blood mononuclear cells of patients with chronic hepatitis C in the absence of serum hepatitis C virus RNA.

http://www.ncbi.nlm.nih.gov/pubmed/8078391?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedarticles&logdbfrom=pubmed


Sept. 1995    Genome detection in liver and peripheral blood mononuclear cells: predictor factors of sustained response in patients with chronic hepatitis C.

http://www.ncbi.nlm.nih.gov/pubmed/8574725?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedarticles&logdbfrom=pubmed



Feb 2007     Presence of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in HCV serum negative patients during interferon and ribavirin therapy.

http://www.ncbi.nlm.nih.gov/pubmed/17314422?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed

[TnHepGuy_]

willing - thanks for posting the extended excerpts from Lin and Gallegos. They help flesh out and explain things much greater than the abstracts. The interesting conclusion (for me) from Lin is that sterilizing immunity "may" come over time. That's a big question mark there, but also hope.

In Gallegos, they reference [22] as a relapse study of long-term follow-up of SVR showing an 8% figure. This is a lot higher than I usually see mentioned. Do you the name of the referenced paper?


CoWriter - thanks for the García-Bengoechea paper. It, too, has been added to the "Occult Health Page" (though the bottom links are now dropping off the page as I add newer ones. Looks like I may have reached the posting limit. I have an e-mail into MedHelp IT to hopefully find a resolution). As far as the conclusions reached, this paper is from 1999 and as 'willing' mentions above in his commentary on Gallegos, it's possible that one factor effecting the data here is that the patients examined were treated w/ mono-inf (as opposed to peg + riba; or being spontaneous clearers, etc). Also, the RNA testing of the PBMC's was most likely done without mitogen stimulation, which (as also mentioned by 'willing' above) could possibly detect greater % rates of cell infection via negative strand findings.

TnHepGuy

[TnHepGuy_]

Thanks for the additional papers. If you find more, please send them to me via a PM (I don't check all the threads, so I could very easily miss your postings). I won't be trying to add these latest ones to the Occult page just yet, not until I get some sort of resolution from the MedHelp folks. No sense just having them (or others) keep dropping off the bottom of the page. I will save them to my Word doc that I keep as a master list.


TnHepGuy

[DoubleDose]

Many thanks for the documentation above.  These studies clearly put clinical research and scientific observations as strong supports for their commentary and conclusions. What they are stating is exactly what I think we must remain 'open to' in our thinking regarding HCV, tx, and SVR.  This is just about all that I was trying to say at the top of this thread....that some people MAY BE at risk for re-activation of the virus after long standing SVR, in special, and usually very unusual circumstances.  But it is re-activation indeed, NOT reinfection.  Rare as it may be.

  The other issue that needs further study is what impact the remaining 'persistent virus' in a state of 'remission' has on our bodies, and immune systems.  Although there are major benefits and health improvements gained from SVR, we still do not know if there is a very long term negative impact from this hidden virus.  I personally believe that the issue deserves continuing study, and that SVR's also should be made aware of 'potential' risks, in very rare circumstances' to their SVR status.  It would allow for more informed choices.

DoubleDose

[CoWriter]

"and that SVR's also should be made aware of 'potential' risks, in very rare circumstances' to their SVR status.  It would allow for more informed choices"

I really doubt that people that cleared the virus on their own are encouraged to do any sort of follow-up.  

[willing]

mike: makes sense; hard to see why else they would recommend continued monthly testing. I would expect current heptimax and labcorp tests are close to the limit of what can be learned by scanning a couple of mL of serum and that the future of commercially-available, sensitive blood tests will be ones that actually use the cells in the collected sample rather than discard them (and Jim and I can stop arguing about whether VL tests measure infection..)

tn: yeah, that caught my eye too. Their reference 22 is:
"Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon." (10365802)
http://www.ncbi.nlm.nih.gov/pubmed/10365802
which seems a bit dated (there are newer long-term follows ups available). Also, these were follows ups to nonPeg tx; if the hypothesis is valid, the peg-SVRs would exhibit a lower relapse rate.

BTW, I wonder whether in referencing pubmed papers in posts,  the title and pubmed id are a better pointer than the url.

coWriter: thanks for that 1999 paper. It's interesting that the recent Gallegos-Orozco paper didn't reference it in their citations; they should have!  I haven't been able to get access to the full paper but am curious to see how the methods used compare to the more recent work.

DD: One twist I see in this is that it seems to argue for a very long ifn taper: eg  assuming und at w12, one might be able to safely start reducing ifn at 24w but should keep taking it for at least 72w.

[alagirl]

DD - No, I do NOT "get the nuance."  I think Dr. Shiffman is pretty unequivocal when stating that his view of successful tx is SVR, which constitutes a "cure" and enables patients to "effectively... put their disease behind them."  Not, put their disease behind them, and "oh yeah, I forgot to tell you but it might pop up again sometime."  That's why he followed them for seven years instead of just declaring after six months that SVR was a cure.  He wanted to make sure that SVR was a solid item.  It's disingenuous to say that his study was only saying, or trying to say that SVR or a cure was for six months to seven months after tx.  What he was trying to say, and what he DID say, in my estimation, was that he felt it was appropriate to call SVR a cure if there hadn't been a relapse six months after treatment.  That would NECESSARILY RULE OUT relapse in the future.  

"I really don't care much one way or the other"

Its ok to have a strong viewpoint on either side of this issue (I sure do), just don't try to blow smoke up my dress about objectively seeing both sides of this issue when you really strongly feel only the persistence viewpoint has merit.  I think you care very MUCH about this issue and you feel persistence is proven fact, not just that we should remain "open to" it, as you've said.  

After weighing all options on what is being called "relapse," reinfection is the most logical explanation to me.  I think there is a lot occult of drug use out there, as well as many additional other ways people pick up hep c, surgi centers, nail salons, I could make a list, but we already know them anyway, and when you are talking about a study with a thousand people (or any number really) and half are former IV drug users, I just don't think its a mystery when over a period of a few years a small fraction of them show up with the same strain of hep c again, garnered from the same activities with the same friends.  I'm just surprised, frankly, that it doesn't happen a lot more often.

And I'm open to being wrong about this, but in my cynism about human nature, I just think that the most logical thing, and the easiest way for there to be a second infection, is that their initial infection was due to more than just a youthful indiscretion.  But.  Let's say that I AM totally barking up the wrong tree, and there IS a way for relapse to occur if the immune system is weakened - typically via some type of drug therapy.  If that's true, it is happening on SUCH a small scale that it still seems, to me, as though SVR is tantamount to a cure.  I mean, it would suck to be in that 1 or 2 percent that fails an extended SVR, but you've got great odds that it WOULDN'T be your particular one or two percent, so its not something I would tend to worry about very much.  (Your much greater concern (and where I would put my energy) would STILL remain in not reaching SVR in the first place, instead of worrying about keeping SVR once you got there.  The odds of keeping SVR, at 1 or 2% failure, if that really were to be happening, would still be negligible in the grand scheme of things).

And there have to be a lot of people who have SVR and later get cancer and treat it (and don't many here on this board - and off of it I'm sure - use biologics like methotrexate and rituxan - THOSE lower your immune system as well don't they?  And hey, I AM asking here, because in fact, I should begin one of those within the month - so I really would like to know anyone's experience on any of those, methotrexate, enbrel, rituxan, humira...), so even if it IS true that this can happen (and still, really difficult for me to see), but if it IS, it must not happen to very many people.  

I approached you the first time, I think, pretty rationally and politely, but I just found your response back to me on this issue to be mocking in some of the things you said to me, and while presenting some research that was on point which I read and which I am willing to consider, failing to concede that Dr. Shiffman (even if you don't agree with the guy) considers SVR to be a cure and trying to make his study and view somehow seem to be something else.  I think I was more respectful than that in my approach to you and I'm not sure why you needed to respond that way.  And I'm sorry you felt I was long winded.  I merely tried to answer your points so I can better understand your point of view on this.  Honestly, sometimes though, it almost seems like you WANT to believe you have "virus replicating" in your body.

You say: "I do NOT think, though, that I have been proven to have absolutely eradicated all viral replicating copies anywhere in my body.  It may be true, but research keeps showing otherwise."

And you say: "If you have a problem with that, speak to the many 'persistent HCV', and Occult HCV researchers, not to me.  I didn't run the amplification studies."

We are not back in school.  I don't have a "problem" with anything.  I am ALWAYS happy and grateful to read any research put forth by you or anyone else and to learn more about this disease.  I don't need to go "talk" to anyone.  We just happen to have different viewpoints on what the research means.  For the record though, I may have misinterpreted it, but I don't think the studies DO show that EVERYONE with SVR has virus replicating in their body.  

"But it is re-activation indeed, NOT reinfection.  Rare as it may be."

Again, it is my opinion that you seem to be saying something with certainty that the scientists are not.  Again, unless I am reading things incorrectly, they have certain findings and there are different explanations, including re-activation.

[alagirl]

six months to seven months = six months to seven years

oy! ;)

[alagirl]

can-do, thank you for fixing my post for me above.  I didn't see my mistake until today, I'm glad you were watching out for me.  I'm always replete with typos, wordo's, sentence'os - you get my drift! :))

[can-do-man]

just don't try to blow smoke up my dress................... Now that was funny.

BTW, I'm the one that screwed your post up, not you. And i'm not "just blowing smoke girl" :)........... Take care

cando

[DoubleDose]

I think you are either not reading very carefully what I am saying, or you are just misinterpreting it:

1. I agree SVR is a 'cure'.
2. A 'cure' doesn't state that the virus could never come back under any circumstance, and I have not seen one doctor say that, nor have they claimed absolute, and total eradication.
3. The studies, referenced above, clearly demonstrate reactivation of the virus, and though you may disagree with the study results, they are what they are.  
4. I AM still open to either the concept of 'persistent virus' OR 'eradication' being true.  I just want unequivocal proof of either one.  
5. The great majority of research studies in the past three to five years demonstrate what the researchers have labeled 'replicating persistent virus' in many if not most SVR's.  That's why I currently give more credence to the 'persistent virus' theory and research conclusions.  I am open to either being proven true.  
6.  I still think that Shiffman is not saying thet 'cure' is equivalent to absolute, and total eradication of the virus, and I do NOT see him saying that no SVR could ever have a late relapse (after two years post-SVR).  Please show me where he says either of the above.
7. I did not think that I was being either disrespectful, or mocking, at all.  If that's how you took it, then I apologize.
8.  I respect your opinion about SVR being an absolute thing, and that the virus can never come back, but I thought we were posting about, and discussing actual scientific research that would support either view.  Opinions are fine, but I think the above listed studies are pretty clear, and are written by HCV medical experts.  
9. When I 'blew smoke' I really did not know that you were wearing a dress.  I would have just 'not inhaled' had I known!  
10.  Talk about being 'locked into a position regarding 'eradication'...do you hear yourself?  Do you believe that you are being at all objective on this issue.?
11.  And finally and unequivocally, I would really, truly, absolutely, LOVE to have the total eradication hypothesis proven to be the real thing...the final outcome...the truth.  Honestly.  I just don't see the research yet that backs up the concept.

DoubleDose

[alagirl]

DD - "All I saw was two people making a claim that the reason for all relapse cases must absolutely be one of the two situations described above.  Is this what you call proof?"

I don't believe I've EVER been so absolutist.  I really don't.  I do have an opinion about it though, sure.  I don't appreciate the way you've been talking to me - so if I seem a bit hostile the last couple of posts, at this point I am.  

"Pointing out a few rare cases of relapse, as you describe myself and mikesimon as doing, is not at all off-base in my opinion.  If TRUE relapses can be documented at all, in any real SVR's, even just one, then I think that the exception may indeed prove the rule.  Why does immuno-suppression sometimes cause the virus to return?  Did you have an answer for the doctors and researchers?  We should get you their e-mail address.  They will be anxiously awaiting your explanations! "

You have NOTHING in common with MikeSimon that I can see.  Mike S. presents research and when we disagree he argues calmly and sensibly about theories instead of getting hysterical and sarcastic.  And an exception does not "prove" a rule anymore than a zebra proves a horse, and there are no researchers waiting for our phone calls with baited breath.  In fact, the researchers know that there aren't any proven answers on this precisely because of the low number of anecdotal cases thus far.  That's why they say things like, "suggest that, and probably" instead of using the word, "absolutely" or "proves that."  They can speculate right now about what is causing their findings.  And we all have our own opinions about it.  Nothing wrong with different opinions.  

"The other issue that needs further study is what impact the remaining 'persistent virus' in a state of 'remission' has on our bodies, and immune systems.  Although there are major benefits and health improvements gained from SVR, we still do not know if there is a very long term negative impact from this hidden virus"

For me, the vast majority of research shows that SVR is durable and I don't think we can just flippantly call it "remission" when even the scientists and doctors don't call it remission and don't use the term "hidden virus."  I think using terms like that do much to feed the bias against anyone who has ever been infected with hepatitis c.  I certainly am not going to think of myself as someone who is still loaded with "hidden virus" or someone who is "in remission."  I am SVR, and just to be safe, I'll give it until a year after I finished my tx, but after that I am going to consider myself CURED.

[alagirl]

3. The studies, referenced above, clearly demonstrate reactivation of the virus, and though you may disagree with the study results, they are what they are."  

To you they seem to suggest that.  I think they are open to interpretation.  But I have already stated my opinion on how I lean on the interpretation, so I won't bore everyone again.

4. I AM still open to either the concept of 'persistent virus' OR 'eradication' being true.  I just want unequivocal proof of either one."

I think we will get there in terms of an answer on this - maybe not as soon as I would like - but it will happen, and I don't think it will be terribly long in the future either with all of the research being done right now.

5. I'm positive I don't agree with that.

6.  I am simply saying that I think Shiffman is making the case that SVR is a cure, and that he wouldn't agree with persistance.  I am not going to participate in putting words into the guys mouth, and I wish you wouldn't either.

7.  No problem, if I'm mad, I'm probably just going to get mad back after a while.  Which I hate, but eventually it happens

8.  You know as well as I do that there is a ton of research on the durability of SVR, I am not going to repost it all.  That was just one example of many studies/articles from a lead hepatologist at a transplant program

10. You have not once entertained the idea that persistence might not be at work here, I have in each entry I've written allowed that persistence might be at play and written that I just didn't think it mattered that much if it was due to the 1-2% low amount of whatever it is re-infection or relapse.





  

[alagirl]

One twist I see in this is that it seems to argue for a very long ifn taper: eg  assuming und at w12, one might be able to safely start reducing ifn at 24w but should keep taking it for at least 72w.
--------------------------

72 weeks of interferon.  aggh!  

[DoubleDose]

I do understany your personal need not to feel 'infected' or loaded with hidden virus, etc.  I do think that this concern is exactly what is fueling your zealot-like need to believe that everything is as you want believe it is.  I do not sense an objective point of view at all from you, and I am sorry if you do not like my opinions.  You seem to become very inflamed and offended when other points of view are expressed, and I understand exactly that you do not like my persistence on this subject (pardon the pun, I couldn't resist).  But at least, please, have a little bit of a sense of humor.  You take everything as an attack.  I don't believe that I was guilty of ANYTHING remotely close to insult or mockery.  Maybe you just have an emotional attachment to this issue, as you seem to state above pretty clearly.  Let's agree not to discuss it with each other, and maybe that way you will not feel offended.  My approach is not going to change in dealing with the possibilities out there.  

DoubleDose

[alagirl]

DD - please don't project your neuroses onto me.  My formal education is in psychology and I don't need your dimestore analysis.  It seems as though you are the one insistent on worrying that your body is fully of replicating virus and fretting that people aren't doing enough "research" to see whether or not its making you sick long-term.  That was in your post was it not?  I'm not now, nor have I ever been, worried about my SVR. I can't understand why anyone would spend so much time worrying about a topic that potentially, even if it were re-infection would only affect 1 or 2 percent of all SVR's.

And you were also the one getting hysterical about everyone attacking you, such that YOU started getting flip and sarcastic with others, telling us to call the researchers, etc.  A couple of examples:

"If you have a problem with that, speak to the many 'persistent HCV', and Occult HCV researchers, not to me.  I didn't run the amplification studies."

Or

"Did you have an answer for the doctors and researchers?  We should get you their e-mail address.  They will be anxiously awaiting your explanations!"

So ok.  If you don't feel that you can maturely debate this topic, or others, with me, without it sinking to this, I agree, we should perhaps not discuss things.  I have no problem discussing things, however, with you or with anyone else.

[CoWriter]

"When I 'blew smoke' I really did not know that you were wearing a dress.  I would have just 'not inhaled' had I known!   "

ROFL

[IAmTheWalrus]

A little off the subject here: What was the original question? Drinking after HCV and cirrhosis! Whether or not alcohol, immunosupressive drugs, or small toads can cause reactivation of the virus, the answer is that your father should not drink. Cirrhosis leaves permanent damage to the liver, and that liver will always be impaired to some degree. Alcohol causes liver damage, so prudent advice would be to stop the alcohol intake.

Let the debate on occult hep c rage on! It is very interesting.

[can-do-man]

alagirl.......just don't try to blow smoke up my dress

DD...........When I 'blew smoke' I really did not know that you were wearing a dress.  I would have just 'not inhaled' had I known!
-----------------------------------------------------------------
Makes me think of the movie by cheech and chong..... Up in smoke..... Now that was a good movie.

[mremeet]

Ala - You go girl. I was done with this thread because it’s descended into the usual re-warmed, one sided, yahoo prattle we’ve discussed ad nauseam again and again before. And when these guys are pressed on the issue of reinfections constituting a sizeable proportion (if not the vast majority) of the 1-2% “relapsers”, we get the incomparable: “Oh if it’s not in a study, it can’t be trusted!” Implying studies are tantamount to sacrosanct biblical scripture. If I had a dollar for every study I’ve read that implied or directly stated something that later turned out to be complete hogwash, I’d be a millionaire. If I had a dollar for every study I’ve read that said one thing, only to be countered by another study that said the exact opposite, I’d be a multi-millionaire. Blind, selective adherence to studies (that just happen to agree with your preconceived notions, pet theories etc), especially published anecdotal accounts without carefully reading them and THINKING, is a mistake. For instance, here’s a few choice quotes from willing’s Lin 08 paper text excerpt above:

“Protective immunity can be overcome by immune suppression, well illustrated in an IVDU that had previously cleared HCV, but developed persistent chronic HCV infection after becoming HIV-1 positive [Mehta et al., 2002]”

and later…

“Virological relapse in our two patients may have been the result of re-infection. However, disease recurrence was associated with the identical genotype in both cases…”

Now, lets think about the first example just for a moment. An IV drug user who was first infected with HCV via IVDU. He managed to clear the HCV virus, but then later caught the HIV virus by continuous IVDU (i.e. needle sharing). And, low and behold, after getting HIV, he came down with HCV again – well, surprise surprise! Hmm…but, *how* did he catch HCV again? Oh no, he didn’t “catch” HCV again, he “relapsed”. And we know he relapsed because HIV is an immunosuppressive disease, which allowed his HCV to “reactivate”. Smart these guys are, not much gets past them. But wait…isn’t a much more likely scenario that this guy was simply reinfected? He is after all a chronic IVDU, he caught HIV just like he caught HCV: by continuing to share needles with other infected users – maybe even with the *same crew* he got HCV from initially in the first place. This clearly means he could have quite probably picked up HCV AGAIN instead of experiencing a “relapse” (in fact, in all likelihood it was multiple re-exposures). And if the argument is that it’s a likely or “proven” relapse simply because it’s the same genotype, what malarkey! Just because an SVR comes down with HCV again and it’s the same genotype, that doesn’t prove in any way shape or form that it was a relapse instead of a reinfection!

Furthermore, many junkies commonly use with the same people (or person) over prolonged periods of time (often lasting many years, and can even involve husband-wife partnerships). Here’s a perfectly plausible scenario that ties into something also stated later in another excerpt:

1. Junkie A does not have HCV.
2. Junkie A starts regularly using with junkie B who is infected with HCV.
3. Junkie A is infected with HCV from sharing needles with junkie B.
4. Junkie A temporarily stops using and gets treated for HCV.
5. Junkie A SVR’s.
6. Junkie A goes back to using with junkie B (who has been “warehousing” the same virus that originally infected junkie A)
7. Junkie A is reinfected by needle sharing with the same viral strain he had contracted before from junkie B.
8. Researchers run sophisticated genomic viral tests on junkie A’s cryogenically stored virus prior to his treatment for HCV (i.e. prior to his SVR-ing). This testing establishes a viral fingerprint for his specific virus (not just his genotype).
9. Researchers then run sophisticated genomic viral tests on junkie A’s virus after his “relapse”. This testing reveals that the viral fingerprint for his specific virus (not just his genotype) is the same as that tested in step 8 above.
10. “Researchers” (this would include willing and dd, of course) then “scientifically” conclude that junkie A has “relapsed.” They “know” this is true because the genomic tests reveal the same viral fingerprint (i.e. AHA! it’s a match! Ergo RELAPSE!).

Like it or not, reinfections do happen guys. Clearing the virus naturally or via drug therapy does not impart immunity against reinfection. Reinfections are a scientifically proven fact, they’re not only possible, they happen. And who gets reinfected? SVR’s and the naturally cleared get reinfected, that’s who. By definition they’re the only ones that CAN be reinfected. So unless you guys are stating that NO SVR’s are reinfected (which would be a very foolish thing to suggest), you MUST make room for them within the 1-2% of “relapsers” we are discussing. Again, it’s not a question of if, ONLY a matter of how many. And yet not a one of you has acknowledged that above – not one of you (so much for your “scientific objectivity”).   cont....

[mremeet]

And it’s also funny how these guys are so “scientifically objective”, and yet never post the following links listed below (except for tn referencing them on his page, thanks to him for that):

http://www.ncbi.nlm.nih.gov/pubmed/18593587?dopt=Abstract

Eradication of Hepatitis C Virus in Patients Successfully Treated for Chronic Hepatitis C.

Serum HCV RNA remained undetectable (1300 samples), indicating that none of the patients had a relapse. HCV RNA was detectable in 2 of 114 (1.7%) liver specimens, and in none of 156 PBMC specimens…. CONCLUSIONS: In this large cohort of chronic hepatitis C patients, SVR was durable up to 18 years after treatment cessation, in addition to fibrosis stability/improvement (88%) and cirrhosis regression (64%)…This result strongly suggests that SVR may be considered to show eradication of HCV infection.

http://www.natap.org/2008/EASL/EASL_77.htm

SVR Eradicates HCV   SUSTAINED VIROLOGICAL RESPONSE IS ASSOCIATED WITH ERADICATION OF HEPATITIS C VIRUS AND DECREASE IN ANTI-HCV TITER IN PATIENTS TREATED FOR CHRONIC HEPATITIS

Background-Aim: Hepatitis C virus (HCV) eradication, in patients with chronic hepatitis C who achieve a sustained virological response (SVR), is still controversial. In this study performed in patients with chronic hepatitis C who achieved an SVR, HCV-RNA was measured in serum, peripheral blood mononuclear cells (PBMCs), liver and anti-HCV antibodies titers were assessed, during follow-up.

Background-Aim: Hepatitis C virus (HCV) eradication, in patients with chronic hepatitis C who achieve a sustained virological response (SVR), is still controversial. In this study performed in patients with chronic hepatitis C who achieved an SVR, HCV-RNA was measured in serum, peripheral blood mononuclear cells (PBMCs), liver and anti-HCV antibodies titers were assessed, during follow-up.

Results: Patients were followed up for a mean of 3.5±2.4 years (range, 0.5-17) years.

Serum HCV-RNA remained undetectable in all the patients (1050 samples).

None of the patients had detectable HCV RNA in the PBMCs or in liver.

The mean anti-HCV titers were 93±19 IU/ml and 45±21 IU/ml, before therapy and on the last serum sample available, respectively (p < 0001).

The most significant decrease was observed with anti-NS5 antibodies (p = 0.001); anti-c22 antibodies remained unchanged.

Normal serum ALT levels were maintained in 94%, fibrosis stage was improved in 57%, stable in 32%, deteriorated in 11% of the patients.

Regression of cirrhosis was observed in 7 of 10 patients.

Conclusion: In our 278 patients with chronic hepatitis C and SVR, evaluated up to 17 years after treatment cessation, none demonstrated late relapse or the presence of HCV RNA in serum, PBMCs or liver. HCV antibody titers showed a marked decrease. These results demonstrate a durable response to IFN alpha 2b or PEG-IFN alpha-2b+ribavirin and indicate that SVR is associated with HCV eradication and progressive decrease of anti-HCV.

http://natap.org/2008/HCV/030508_01.htm

PBMC Not A Reservoir for HCV for Patients Who Clear HCV RNA, Study Reports Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia

On the basis of our results, the clearance of HCV from PBMC therefore appears complete in both spontaneously aviremic and successfully treated seropositive blood donors...These results indicate that PBMC-associated HCV is unlikely to be maintained as a viral reservoir with the potential to rekindle plasma viremia in aviremic subjects as determined by plasma TMA assays. This conclusion is supported by a recent analysis that similarly failed to detect PBMC-associated HCV RNA in 9 spontaneous and 2 treatment-induced aviremic patients.[16] A greater than 90% rate of clearance of HCV RNA in the liver of sustained virological response also indicates that a long-lived hepatic reservoir is unlikely to exist.

Conclusion: Our results indicate that PBMC are unlikely to serve as a long-lived reservoir of HCV in aviremic subjects.

http://www.annals.org/cgi/content/abstract/127/10/875?ijkey=9fd1a2b08287a89cb904c3420e7dcd5103e9e8a1&amp;amp;amp;amp;keytype2=tf_ipsecsha

Long-Term Histologic Improvement and Loss of Detectable Intrahepatic HCV RNA in Patients with Chronic Hepatitis C and Sustained Response to Interferon-  Therapy
Conclusions: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-  therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement. cont...

[mremeet]

http://vir.sgmjournals.org/cgi/reprint/78/11/2747.pdf

Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication.

Peripheral blood mononuclear cells (PBMCs) from 27 hepatitis C virus (HCV)-infected patients were analysed for the presence of HCV negative strand RNA with strand-specific Tth-based RT–PCR. No negative strand RNA was detected in any sample, and positive strand HCV sequences amplified from PBMCs were identical to those found in serum. These findings suggest that HCV does not replicate in PBMCs…

end study references...

In closing, there’s more studies and information available online than this that supports eradicative outcomes post SVR. It isn’t a pet project of mine to track down and research this stuff and keep file folders on it like the viral persistence crew does (selectively, though). I don’t really care that much about it either way. I’m comfortable with thinking of myself as being cured for a variety of very good reasons (even if my SVR turns out to be not “sterilitically” eradicative). But for anyone else reading all this stuff who is confused about what to make of it all, many researchers and doctors leading in their field also feel strongly that eradication does happen after we SVR (and freely use the “cure” word in an eradicative sense). There’s a renowned and famous leading hepatologist on this very forum who answers questions named Dr Douglas Dieterich. Take a look at what he says in these posts about a few of the things we’ve been discussing above:

http://www.medhelp.org/posts/show/582716

Q: I was treated with peg interferon three years ago. I was none detectable at six months and one year. Several months a go I relapsed on meth after almost five years clean. A few times I shared needles,I cleaned them with bleach. I thought that if I had the antibodies I couldn't be re infective.I went today for a blood work and the doctor told me I could of easily been reinfective. I am again in recovery (from drugs) but if Ive been reinfective, is treatment still a option? I am 50 years old and in vary good shape. I have a four week wait for my blood results, but any info on reinfection and prognoses would be appreciated.

Dr Dieterich: You certainly can get reinfected and we have seen it here at Mount Sinai several times. Yes you can be successfully re treated too. Make sure you are successfully treated for the drug problems, though before embarking on another treatment course.

http://www.medhelp.org/posts/show/537424

Q: Cured or in Remission - once in SVR? Will the virus ever come back?

Dr Dieterich: Cured

http://www.medhelp.org/posts/show/564454

Q: QUESTION FOR DR. D: I HEARD THERE IS NOW A TREATMENT TO CURE HEP C, IS THIS TRUE? LAST I HEARD ABOUT 5 YEARS AGO ONLY AVAILABLE WAS THE INTERFERON W/REBETRON TREATMENT WHICH DIDN'T HAVE A VERY GOOD CURE RATE?!  THANKS ~ JULIE

Dr Dieterich: There has been a cure for HCV since 1991. The response rates have increased steadily from about 6% then to about 60% now. The new drugs that we are using in clinical trials have increased that number to about 70% so maybe that is what you are hearing. The odds are getting better but you are getting older so go get evaluated for treatment now! DTD

[alagirl]

Well, at least two of those appear to have been fairly well attended, which is always nice - makes you feel a little better about the results.

[DoubleDose]

And, YES I have acknowledged the studies you quote, and am fully aware that some of the recent research finds no evidence of 'persistent HCV' in the body.  This is the research that provides me with some hope that the virus may really be eradicated.  I DO acknowledge that research, and their  conclusions.

  I do not, though, see you acknowledge the large quantity of research studies that find contrary evidence, and continue to demonstrate 'replicative virus' after SVR.  For these studies you seem to either 'doubt' their findings, or unilaterally claim some sort of lab error or misreading.  Now if you are going to claim to be open minded, how about the other side of the argument?  No quarter given there from what I keep hearing.  You give total credence to the several studies that conclude eradication, and tend to ignore or repudiate those that used more extensive amplification techniques, and found low level replicating virus.  

So, criticize me for leaning toward the 'persistence' side, (which I do)  while you ONLY trumpet eradication, and the several studies supporting it., all the while claiming to be rational and objective.  

We can let the readers of the thread decide what is objective and what is biased.  You can blow your own horn on this all day long, but there are still two distinct sides to the argument, with plenty of supporting data on each side.  You keep overlooking THAT point. The studies posted above and on the Occult page are ample evidence of this.

Also, OF COURSE I assume some or many of the 2% or so odd relapses after SVR could be cases of reinfection, or faulty testing.  That would be expected random odds, and I do keep this in mind. But not ALL of them.  Without any evidence that they are not a reactivation.  You do the opposite, and without any objective proof, or evidence, you label ALL of the relapses that occur as reinfection or lab errors.  All that I can say is: that is not going to win you a prize in even a grade school science fair, much less in the medical research community.

Its just like when the doctor listens to the HCV infected person's symptoms and is just sure, absolutely positive, that they are all in their mind.  You know these HCV people, they dream up symptoms and exaggerate.  Right?  I mean, its OK to make gross assumptions if you think you know all the answers.  Plus, you don't have to do any tedious analysis or research to get your answers.  Just decide the answers unilaterally.

Sorry to be argumentative, but if you read YOUR posts, I am being very tame.  But I do try to hit the nail on the head.

DoubleDose

[DoubleDose]

And, also, I DO think that SVR is durable...I have never claimed otherwise.  But DURABLE with a rate of 1% to 2% relapses long term.  (some studies show an even higher percentage, up to 8%).  So when you guys say that, with great authority, SVR is a "durable" cure, you are preaching to the choir.  But the exceptions, and rare relapses still exist, and several members offered strong documentation above.  Durable does not mean ALWAYS, or FOREVER.  It means DURABLE.  'Generally strong or lasting'.  No absolutes.  If you ever wore durable gloves, or drove on durable tires, you know that durable is not a forever, or absolute term.  But is is a very positive outcome indeed.

DD

[alagirl]

DD says:

"I assume some or many of the 2% or so odd relapses after SVR could be cases of reinfection, or faulty testing."  "But not ALL of them.  Without any evidence that they are not a reactivation.  You do the opposite, and without any objective proof, or evidence, you label ALL of the relapses that occur as reinfection or lab errors."  "All that I can say is: that is not going to win you a prize in even a grade school science fair, much less in the medical research community." "But DURABLE with a rate of 1% to 2% relapses long term."  "But the exceptions, and rare relapses still exist"


DD - you have mischaracterized what I said, and you have mischaracterized what the studies say.  I am going to attempt to explain my point of view one more time because apparently I have just done a poor job of explaining it.

You say: "I assume some or many of the 2% or so odd relapses after SVR could be cases of reinfection, or faulty testing."  "But not ALL of them.  Without any evidence that they are not a reactivation.  You do the opposite, and without any objective proof, or evidence, you label ALL of the relapses that occur as reinfection or lab errors."  

I have never "labeled" a second infection in someone who has SVR as a new infection or a lab error.  What I have said is that my OPINION is that this is what makes the most sense, given the data from the studies I have seen thus far, and given what I know of human nature and what I have seen in the community and from my days as a social worker.  It seems the most logical.  I'm not super excited about the lab error theory because I think that people are generally getting follow up tests quarterly or every six months for a certain period of time so one bad test result will get caught eventually.  But I think a new infection SEEMS more logical, barring some other study that blows me out of the water.  Where, in that, does it say I'm an absolutist?  Because in considering the options, I tend to lean in one direction?  I'm not dismissing a viremia reservoir that can autoinfect out of hand, I just don't see it as the most likely culprit in these cases.

"All that I can say is: that is not going to win you a prize in even a grade school science fair, much less in the medical research community."

You know, that is just childish and so unnecessary.  Nobody is trying to win any prizes here.  We're all just trying to help each other understand what is a very devestating disease process.

"But DURABLE with a rate of 1% to 2% relapses long term."  "But the exceptions, and rare relapses still exist"

I believe the most likely mode of infection is a new infection when someone comes up with virus in their blood after SVR, but I don't claim that I know beyond a shadow of a doubt that this is how it happens - and I'm interested to see any and all of the research out there on this.  But here, you are saying that these are definitely relapses, when even the doctors conducting most of these studies don't say that.  They say things like, "it would seem to suggest that," or, "this may mean that."  You seem to feel ok attaching the relapse label to it though (speaking of labels).  

And while we are attaching labels, let's attach a definition to the word durable.  While I appreciate your attention to my vocabulary, we apparently see the English language a bit differently.  Did I mention that I minored in English?  No?  Oh well.  

As it happens, durable, synonym for the word, "permanent," does mean something that will last and endure the whole way through.  There is no "generally strong" to it.  Its something that will be there for you.  It endures.  I'll tell you, a better word was never applied to our SVR!  I took the liberty of looking up the definitions of the defining words as well.  You know.  Just to save you the trouble. Permanent.  Enduring.  Doesn't that have a nice ring to it?

du·ra·ble  
–adjective 1. able to resist wear, decay, etc., well; lasting; enduring.  
–noun 2. durables. durable goods.  
--------------------------------------------------------------------------------
[Origin: 1350–1400; ME < MF < L dūrābilis. See dure2, -able]

en·dur·ing  
–adjective 1. lasting; permanent: a poet of enduring greatness.  
2. patient; long-suffering.  

[mikesimon]

I am not sure about "prattle" - I do have an open mind.
I sometimes suspect hyperbole though and I suspect that I might see that in your post.

You said:

"If I had a dollar for every study I’ve read that implied or directly stated something that later turned out to be complete hogwash, I’d be a millionaire. If I had a dollar for every study I’ve read that said one thing, only to be countered by another study that said the exact opposite, I’d be a multi-millionaire."

Well, if you have been reading studies every day for the last 50 years - and I think you're younger than 50 anyway - you would have to have read 54 studies every single day that "turned out to be complete hogwash" just to be a millionaire. To be a multimillionaire you'd have had to have read at least another 54 studies a day. How ever do you find the time to post such long posts and still manage all that reading?

Mike

[DoubleDose]

I'll accept your definitions from the book, since I only gave my interpretation of durable.  And, interestingly I also minored in English, and did quite a bit of writing, both fiction and non-fiction.  I guess my durable definition must have come from the 'fiction' side.  But anyway, I was just trying to make the point that I do believe that SVR is durable, but I do think there are exceptions, as shown by the rare relapses documentations. If these exceptions are shown to be real, then we may learn more about viral clearance mechanisms, and how they work.

As long as you and mremeet are strictly saying that it is only your 'opinions' that any relapses that have occurred were from re-infection or lab errors, then I have no issue with that at all.  I just don't think we should confuse those opinions with actual fact, or accept that this opinion has been proven true.  My leaning toward persistence is strictly my opinion, of course.  Not even a strong opinion, but a 'leaning'.  I am open to the future findings of researchers, and will adjust my opinions accordingly.  That is how I try to keep an open mind on controversial subjects.

That's all I have been asking for, by the way, is to let the research finally determine what these relapses actually are, and whether any are indeed a viral reactivation.  I don't think any of us have those answers yet, but there are apparently some strong concerns voiced by several medical teams, in regard to reactivation (as posted and discussed above)

DoubleDose.

[mremeet]

Yes, the quoted excerpt above was hyperbole. It was wise of you to suspect that's what it was. It was unwise of you to interpret it literally as you did afterwards and imply I was being serious. Myself and nearly everyone else often use hyperbole in what we say, so you might want to watch out for it in the future as well (and not be alarmed by it when you see it). For instance, if I say I  was "dead tired" when I was going through treatment - I don't really mean DEAD tired, because dead is dead. Obviously no living person can possibly be THAT tired. Or if someone says "we nearly died laughing", they don't really mean that the EMT's had to be brought out to rescuscitate anyone. It's an obvious exaggeration that's used to humorously make a point. It's not a lie or an inappropriate mechanism for deceit (usually). Hyperbole is ok mike, children and grown adults instinctively understand this without it being literally explained in this fashion. So I hope this explanation helps to clears it up for you. Here's a link that may further explain hyperbole to you as well, enjoy:

http://www.examples-help.org.uk/hyperbole.htm

[DoubleDose]

I know you like hyperbole.....as long as it is just you using it!  You seem to me to give yourself the right to use personal slurs, and mis-characterize others' motivations, or psychological state, but bristle when anyone else uses humor, sarcasm, criticism or hyperbole in response to your comments.  I won't go over your past posts and comments toward me, with the quotations around them, and highlights, etc. other than to say that if you re-read all of your past posts, you will find plenty of examples of what you most heatedly criticize.  If you want a polite, rational, productive discourse then you need to pay some attention to your own act as well.

DoubleDose

[mikesimon]

I think this is a serious subject and deserves serious dialogue - it's an intellectual or academic subject we're trying to understand. Hyperbole in this context certainly doesn't lend any credibility to your argument. The point you were making with the quoted statement was what? That some studies have later been disproved? That is so obvious that it doesn't even need to be said. As adults we all know that. Why even mention that obvious reality - much less feel the need to employ hyperbole.
I am not emotionally involved here. I have no dog in this fight. I would love to believe that SVR means complete and absolute eradication. After all, I am taking immunosuppressive drugs every single day. Intellectually I am not convinced. It's that simple.
Mike

[jmjm530]

Mre: if I say I  was "dead tired" when I was going through treatment - I don't really mean DEAD tired, because dead is dead. Obviously no living person can possibly be THAT tired.
---------------
Thanks for the clarification. Mike was givng me pause with his mathematical model factoring in your age and reading speed against net worth. You now have my attention again :)

[DoubleDose]

Wow, do I ever agree with your comments, especially the last few sentences.  Contrary to what many on the board believe about my views, I REALLY do want to see the total eradication concept proven completely true...valid!  I did feel strongly that this was the case as I entered into my tx'es, but... during the second round of therapy in 2002, I  began reading and absorbing the many disheartening research studies emerging, that were finding some sort of low level replicating, negative strand virus, in long term SVR's.

  I did not want to internalize these findings at that time, as I slowly came down the path to final SVR, but after many reviews and re-readings of the onslaught of these numerous 'viral persistence' studies, I finally realized that there MIGHT be more to the SVR reality that what I had wished for, which was total, and complete eradication.  I slowly began to leave room in my emotional repertoire for this possibility, and came to accept that this(viral persistence) might just end up being ultimately proven true.  I had hoped to see lots of studies directly refuting or contradicting these research findings, and spoke to lots of HCV experts, and nationally known doctors, etc.   I became more convinced that there were no final, or absolutely clear answers yet.  

The contradictory studies that have surfaced, indicating long term findings of 'no persistent virus' have all lacked just one important aspect:  they did not use the most contemporary and highly powerful amplification techniques that the other studies had employed.  I will be more fully convinced that eradication is for real when more studies surface using the most powerful techniques to assess eradication throughout the body, and show convincingly that there is no replicating virus anywhere to be found.  In the meantime, as you said, I am not yet intellectually convinced.  
Bring on the studies!  

DoubleDose

[mikesimon]

Your experience mirrors mine - the changing of my reality as I read new information.
I do find a tremendous comfort in the fact that the experts DO AGREE that SVR appears to be durable, stops liver damage and can reverse fibrosis and possibly reverse cirrhosis. My ALT has been in the low teens (11 - 14) consistently absent any major drug dose changes and my AST is 17 - 21. I get a lot of labs - I see them every 2 weeks.
I would never want to lead anyone to believe that achieving SVR is not the goal or that I would argue against characterizing SVR as a cure. This subject is intriguing and intellectually challenging. I also believe that insight into persistence might shed light on understanding null responders and relapsers and that is extremely important.
Any emotion I might have once had about this subject has dissipated completely or nearly so, anyway.
Be well,
Mike

[DoubleDose]

I would agree with and mirror your statements above, completely.  My experience as well.

DD

[GGraphix]

I think a few of you could use a couple drinks, but thanks I'm learning allot. My question is whether there a point when someone is considered non -contagious. Not to fuel the fire but if cured is 6 months SVR is it than O.K. to give blood. Maybe I did mean to refuel the fire, fight on.

[TnHepGuy_]

re: Blood donation


From the Red Cross website:

"Hepatitis, Jaundice
If you had hepatitis (inflammation of the liver) caused by a virus, or unexplained jaundice (yellow discoloration of the skin), since age 11, you are not eligible to donate blood. This includes those who had hepatitis with Cytomegalovirus (CMV), or Epstein-Barr Virus (EBV), the virus that causes Mononucleosis.

Acceptable if you had jaundice or hepatitis caused by something other than a viral infection, for example: medications, Gilbert's disease, bile duct obstruction, alcohol, gallstones or trauma to the liver. If you ever tested positive for hepatitis B or hepatitis C, at any age, you are not eligible to donate, even if you were never sick or jaundiced from the infection.


Hepatitis Exposure
If you live with or have had sexual contact with a person who has hepatitis, you must wait 12 months after the last contact.
Persons who have been detained or incarcerated in a facility (juvenile detention, lockup, jail, or prison) for more than 72 consecutive hours (3 days) are deferred for 12 months from the date of last occurrence. This includes work release programs and weekend incarceration. These persons are at higher risk for exposure to infectious diseases.
Wait 12 months after receiving a blood transfusion (unless it was your own "autologous" blood), non-sterile needle stick/body piercing or exposure to someone else's blood.
Wait 12 months following a human bite, in which the skin was broken."


David

[jmjm530]

Your question addresses two issues. Can you donate blood after SVR and are you contagious after SVR.

As pointed out, you cannot donate blood after SVR in the U.S. per guidelines posted.

But the fact that these guidelines are in place does not mean you are necessarily contagious -- nor to my knowledge have any studies been done to show that an SVR can infect anyone through a blood-to-blood route, transfusion or not. The closest I've seen is that some of the occult/persistent studies raise the question but go no further.

And to reinterate what has already been discussed on this topic, many, including my two liver specialists believe that when the virus is gone it's gone for all practical/clinical purposes and therefore as an SVR I was told I was not contagious. This is consistent with what a number of others have posted although can't speak for everyone.

You might want to search the Expert Forum as I believe Dr. Dieterich has commented on the issue, but if not, it might be a good question.

-- Jim

[jmjm530]

From the Expert Forum:

Question:  Is someone who is SVR HCV contagious?
Dr. Dieterich: No
http://www.medhelp.org/posts/show/537424

Re Organ Donation:

Dr. Dieterich: You cannot donate blood, but you can donate organs. Seems silly but that is the way it is done. Many people are offered HCV + livers if they have HCV already and there is no real issue with it.
Donate your organs! We should all be doing that and with the Holiday weekend coming up all of us who can should donate blood! DTD

http://www.medhelp.org/posts/show/560506

[willing]

mremeet:
>and yet never post the following links listed below

of the studies you posted,
"Eradication of Hepatitis C Virus in Patients Successfully Treated for Chronic Hepatitis C."(18593587) and "Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia."(18220272 ) have been extensively discussed in recent threads, as well as in this one (see discussion of mitogen/cytokine stimulation in above post "unlike the two recent French and the Bernandin paper,". ). Also, the first twp links  reference  the same study, first as the pubmed journal article then as the EASL conference report.  The other two studies both date to '97. While this does not invalidate them, it's important to check for more recent data. In particular following  Radkowski's publications shows that since 97 he has authored a number  of studies with the opposite conclusion.

Also, I believe the discussion of the excerpt from Lin'08 re the possibility of re-infection misses the point of that citation. The authors in Lin'08 were comparing protective and sterilizing immunity. The case of the HIV-plus individual is cited from
"Protection against persistence of hepatitis C." (11988247).

In that study the authors set out to investigate protective immunity in humans. Previous studies had shown that re-infecting chimps who had cleared HCV results in significantly attenuated infection (lower viremia, higher chance of clearance). This is a tantalizing result as it indicates that though no vaccine exists yet, partial acquired immunity seems to exist. Finding humans who want to be reinfected is a challenge, but, lo and behold, continual drug users rise to the occasion. "We tested this hypothesis in a cohort of injecting drug users in which a natural experiment of clearance and reinfection was taking place."

That is the whole point of the Mehta study was to test for the attenuating effect of previous infection in a population where constant reinfection risk was a given. Their results confirmed the finding in chimps:  lower viremia and higher clearance rate among drug users with hcv ABs than among those with no antibodies. This is was a controversial study, and in fact should be added to the list supporting eradication since part of their data, not shown in the abstract failed to detect HCV RNA in the bx samples of 20 patients who had cleared HCV.

However, I believe  the point of the citation in Lin'08 was simply that protective immunity  can be lost as a consequence of the severe immune-system damage triggered by HIV.

GGraphix: you might ask how many SVRs confident of their non-infectious status would be ready to give a transfusion to one of their kids.

[willing]

Since I think of Radkowski as one of the proponents of the "it's (nearly) everywhere" school, I  surprised by one of the refs mremeet posted above :

"Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication."(9367359)
http://www.ncbi.nlm.nih.gov/pubmed/9367359

and curious about the timing of  his change of opinion on the subject,. Following up citations to the 1997 article shows that
apparently, the turnaround happened fairly soon, see:

"Detection of hepatitis C virus replication in peripheral blood mononuclear cells after orthotopic liver transplantation."(9753352)
http://www.ncbi.nlm.nih.gov/pubmed/9753352

and
"Search for hepatitis C virus extrahepatic replication sites in patients with acquired immunodeficiency syndrome: specific detection of negative-strand viral RNA in various tissues."(9794927)
http://www.ncbi.nlm.nih.gov/pubmed/9794927

Both from '98. The now-you-see it now-you-don't dependence on the strength of the patient's immune response may well be exactly the same phenomenon underlying the discrepancy in the recent  PBMC detection papers depending on whether cells  have/have-not been mitogen stimulated prior to PCR.

[alagirl]

natural experiment of clearance and reinfection
-----------------------------------------------------------------------
boy if that isn't a graceful way to say it...  

Does it appear in all of these cases of suspected "relapse" that there is some type of immune breakdown due to medication or natural state of the person due to HIV or something of that nature?  I'm wondering, because if that's the case then it seems as though even if this IS proven to be something other than error or re-infection, it is something that only has the potential to affect an exceedingly small percentage of all SVR's.  And if so, you would know ahead of time if you were in the risk group.

[willing]

yep, tactful isn't it? (I've been conducting 'experiments' to test the hypothesis that I'm immortal). And people accuse scientists of not having feelings...

I'm not sure anyone knows the answer to that question. Garden-variety relapse seems to happen without any accompanying immune deficit, but most (all?) of the published instances of post-SVR recurrence seem to involve immune dysfunction. In the midst of all the arguing in these threads there's always something new, at least for me. I had never thought of the AIDS-HCV connection as a way of getting information about how HCV interacts with our immune response.