Continuing Questions for Hepatitis Researcher

[DoubleDose]

I thought a new thread would soon be needed, so I opened one to continue the questions from many of us, below, for HR.

One question relates to the issue of Post-Tx 'hyper-immune' syndrome, and potential treatment for this problem.  Several of us seem to have ongoing problems, well after completing tx, and obtaining the SVR.  Issues relate to 'autoimmune type manifestations, joint pains, fatigue issues, rashes, sun-sensitivity, erectile dysfunction,libido issues, lack of energy and motivation, dry eye and sjogren's like symptoms, neuropathy for some, insomnia, etc.  Any potential medications, therapies, or ways to approach these problems will be explored with great interest.

Other questions involved 're-treatment' for relapsers, and issues around optimal dosing, and the role of Ribavirin.  Relapse between 3 and 6 months post-tx has surfaced on the forum, and would warrant some discussion.

Another issue is that of very late relapse after SVR, as in the several cases of patients on immuno-suppressive therapy that became HCV positive again after a good number of years clear on PCR.  Any consensus in the HCV research community as to the validity of these relapses. Do they prove or even reinforce the theories of 'viral persistence after SVR', and HCV being in Remission, or is there still debate on the actual relapses being real relapses???

Other recent questions involver the potential for provoking relapse by having various surgeries (teeth, gum, etc.) soon after finishing tx (in the first year).  Is there ANY logic to this?

Thanks for all replies!

DoubleDose

[Myown]

I know you were serious and I agree with what you said that this is the crazy world we live in.,,BEYOND crazy. But,,,,really to tell you the truth,,,I sorta thought that you would be on the other side of the issue,,,agreeing with the proposition,,don't mean that as a snippy remark or anything,,but your views on things would have led me to believe you would be in favor of it,but you're not and that surprised me,,,your a mixed bag, but so am I. I lean to the right, but not on everything,,you seem(hehe) to lean towards the left, but I guess not on everything,,,so that makes us both mixed. Some would say 'mixed up', but that's okay, everyone can have their opinion, right?
see ya later....

[cuteus]

it wasn't just one girl.  as I posted, they were collecting samples of subjects that spontaneously cleared, were svr by tx or were still infected.  They were paying good money for these subjects. That tells me that they are studying the blood of these people.  There is a lot of behind the scence things that we are not aware of, so we tend to think nothing is happening.  Some of these studies and research don't show up the results for many years.  ALL I said was that we can't presume that no one is testing our blood for clues as to how hcv is working on us.  The fact is, they might be.

as for the spokesperson, poster child, it does seem like there are no auditions going on...but who knows?
be well

[Myown]

Here's one of the articles that speaks of reporting names of hiv cases

http://www.boston.com/news/local/articles/2006/04/23/states_hiv_list_to_require_names/



"The refined tracking system in Massachusetts, which authorities said they hope to have running by the fall, would maintain records about HIV cases within a closed computer network that would be inaccessible through the Internet. Entry would be so tightly limited that not even Cote could get in, the commissioner said."
----------------------------------------------------------------

I wonder if our records of having hep c are "inacessible through the internet?"

[Myown]

lol

[Myown]

Hi Cuteus,
Okay so maybe someone studied a girl at one time or what ever, but I think we would hear something if they were really pursuing this?Everyones energy is in the race to get better meds for hepc which is good, but there are other issues, as DD mentioned, that need attention.

Aids gets alot of money and it took time for this to happen,,but the difference with aids/hiv and hep c is our poster boy is not as appealing to the eye.

Hep c has a dirty homeless IV drug user image,,though we know better,,, the public doesn't.  

Hiv has a good looking gay male as the poster boy. Quite a different picture, wouldn't you say? HIV has all of hollywood financially backing it. Good reps,,Bono, Taylor etc. Both from different corners,appeal to differnt audiences.

Our names got turned into the state that we have hep c. Hiv infected people have not had their names turned in,,,though this has just recently changed. (I believe Vermont is a hold out, but if they don't comply they will loose some federal buckeroos.)

So how did hiv infected get the privlege of not having their name turned in to state all these years?  The answer always was..afraid of discrimination towards them. Well what about us with hep c?? Again look at the posters.

We need a 'new face' on our poster in order to get the deserved attention, but the sad thing is,,most of us want our privacy and anonymity, me included.

[mikesimon]

I'm sorry that I didn't respond - the thread got so long that I forgot about your inquiry. When my anti-rejection was reduced by 70% over a 10 week period my enzymes started to rise pretty dramatically. I thought I was rejecting and went for biopsy. A tiny bit of HCV was detected (30 IU/ml) in my tissue and mild fibrosis (stage 1 to 2 on a scale of 1 to 6) was seen. Previously I was at stage 0 but I treated for over 3.5 years so the virus never had a chance to do much damage. I was transplnated in June 2000 and started TX in late July 2000. My thought on the low dose Pegasys and ribavirin is that it is intended to halt any ongoing fibrosis and maybe reverse the litle I have with some real good luck. And I imagine that it also provides some insurance against an increase in replication. But since the virus replicates at ten to the twelfth power and I had been off TX for 2 years it doesn't appear that replication had ever been an issue. My surgeon said it was my immune response to the HCV (since the dose reduction stimulated my immune system) that caused the enzyme elevation. And with and ALT of 458 and only 30 IU/ml HCV in my liver it appears to me that a lot of bystander cell death was occuring and that is likely due to my immune response which up until the dose reduction was not an issue. My enzymes were alsways in the teens or very low twenties on a rare occasion and if your clinic is like mine you know how frequently they test.
I have said here many times that Pegasys was far easier on me than was Peg-Intron. That being said, Pegasys even at half dose is no fun. My biggest issue is the psychological overlay that seems to accompany use of interferon. The easiest way to explain it is that my life is sort of flat. I don't get excited about anything whereas when I'm off this stuff I am quite energized with life. Since my ribavirin dose is only 200 mg daily anemia isn't an issue at all and that makes this mini TX tremendously easier on me. I still look forward to getting off of it though. As far as manitenance goes I have heard of half dose Pegasys being used but I can't recall a miniscule amount of ribavirin ever being mentioned as part of the maintenance but I forget a lot of this stuff.
The one thing that I want to stress is that I have never been serum detectable since 2003 except upon biopsy and my numbers have looked beautiful until the AR dose reduction.
I wish you great luck.
Mike

[Eyedeas]

Just my 2 cents, but I dont usually have the energy, attention span, or the time to read every thread and these generic headings tend to get skipped.  I usually go for those threads with titles that interest me.

Like I say, just my 2 cents.
Kim

[Forseegood]

Return...I second your sentiment on this being a very good, educational and supportive forum -- when it doesn't go off on meaningless, non-productive negativity...great post...

Mremeet: just wanted to say that I too have been anxious and hopeful about your progress, as many here I'd suspect (you being on the Vertex trials, etc)...I'm really, really glad that you seem to be progressing apace...ON TO THE SVR BUS FOR YOU!!!! Please keep us posted on your progress, inquiring minds and all of that!

[Hepatitis Researcher]

A quick comment on your rashes, frequency etc.:
In insider meetings re the development of the Vertex or other HCV Proteinase inhibitors one of the biggest obstacles was that the shallow groove of the HCV Proteinase requires a blocking molecule much larger than for the HIV Protease inhibitors. Because of the large size, inherent immunogenicity is strong and such stimulation of the B cell system leads to Allergies, rashes, immunecomplex problems. It would be interesting to see if a Raji cell or C1q immuncomplex assay ( both are routinely available, no reseach setting) result parallels the intensity of the clinical symptoms and if the use of the protase inhbitor intensified the level of immuncomplexes.

BTW one has to admire the quality of thinking and stamina that your above contributions require considering your current ordeal.

[mikesimon]

American Journal of Transplantation 2005; 5: 1909

[jmjm530]

Sounds like a rough ride. Still, your nine week goal seems doable and I think you should have a reasonable expectation of SVR regardless of what you stated. Don't remember your liver stage status, but don't blame you one bit for waiting for another tx approach assuming a relapse and that you don't have advanced liver damage. From personal experience, skin problems can be the absolute worse and mine didn't start normalizing till six months post treatment. Hopefully, your case is not the norm with VX-950 or things may not be as rosy as hoped for. Time will tell.

Be well and hang in there. Don't know if I mentioned "Banetar Bath Oil" before but it did help my itch and scaly conditions somewhat. It's OTC although it may have to be ordered.
http://tinyurl.com/ycl8dh  If you do go ahead and order it, you don't rinse it off, just leave it on overnight after the soak.

All the best,

-- Jim

[mremeet]

Hey jim, hope you're doing well, thanks for asking how I'm getting on. To give you a quick update, I'm still blinded currently in week 15 (I think). So far no indications of what my VL is, but according to my study nurse she says "no news is good news." By that she meant that if viral re-emergence was observed after clearing earlier in treatment, I would have been unblinded and discontinued from the trial (because it's not working). Since my lengthy dosing of prednisone and the solumedrol shot, I was worried I might have become detectable during that time (having also stopped the VX early and briefly interrupting riba dosing too). But I received blood tests during the worst parts of it (including blinded PCR's) and haven't been discontinued. This implies I made it through maintaining UND status, which would really be quite remarkable so early in treatment - especially considering the extensive use of steroids and various study/SOC drug dose interruptions. It would suggest the VX is indeed potent stuff...but I'm certainly not counting my chickens just yet.

As far as the rash is concerned, I've been off prednisone for about two weeks now. I still have a rash, but it is much more subdued compared to what it was. I guess what I have now is a classic riba rash. A lighter red rash, with dry insanely itchy skin with blotchy "hotspots" on my hands, feet and ankles. I suppose those are the resonating after-effects from the big bad systemic VX rash I was fighting earlier. I use clobex steroid cream to deal with those, seems to work ok. Just lately I've had to cut back on my riba, the rash and hot pin pricking "prickly heat" has been too much lately. I simply cannot take this feeling. The incredible itching, the crusty ears and maddening itchy ear canals. I've itched my eyebrows clean off my face. My scalp is dry and flaky and intensely itchy and burning, and now my hair seems to be falling out. All I do is lay in bed, take atarax and sleeping pills and try to remain as still as possible. Then muster enough energy and willpower to put clothes on over my skin and go to work. Unless something changes and the QOL improves at least a little, there is absolutely no way I can go 48 weeks. Right now I just dream and fight every day to make it to 24 weeks. That's my goal, 9 more weeks. I hope I can make it, but I'm dreadfully pessimistic nearly every day that I have it in me.

If I fail to get my SVR (which is looking quite likely at this point), I plan on trying again in a few years with peg and another PI (now that I'm allergic to VX) sans riba. I think I could handle this treatment without the riba. The riba is the real side effect killer, from my experience. If we can just get rid of it while hopefully enhancing current effectiveness, then we'd be getting somewhere.

Lastly, I was getting my blood drawn from our study lab tech and she said "there are four of you all with that bad rash". She explained that there were four people in our group that had a bad rash like mine. I thought that was interesting because when I asked my study nurse that same question, she said that there was no one else who had a bad rash in our group. I guess Vertex tells them to keep their mouths shut on matters of that nature. Plus I heard of another person in pln's (pam's) group that was discontinued from a "horrible rash like nothing we've ever seen". Also I noticed on my consent form that it says under "possible risks and discomforts" section: (when referring to 14 day VX mono-therapy trial results) "In the second study (8 subjects), the most common side effects considered possibly related were skin problems such as dry skin, itching, redness/rash (38%), and headache(25%)." I'm starting to suspect that rash problems from the use of VX may constitute a fair percentage of those who take it, although hopefully/thankfully still in the minority.

Take care.

[DoubleDose]

I understand where you are coming from, and let me be clear about this: I was not trying to question your logic or knowledge on HCV, but merely demonstrating the point that most medical professionals in the HCV world have been pretty 'closed-minded' about various possibilities.  Some of these things are slowly proving to be realities, like finding positive replicating virus in long term SVR's, and those who spontaneously cleared, within PBMC, liver tissue, lymphatic system, etc.  Slowly these research findings are becoming more accepted, and now in HCV literature where you once saw terms like 'eradication', you are more likely to read about 'keeping the virus at undetectable levels' on a long term basis, etc.  Many of the liver transplant specialists also believe that the virus often persists at low levels in the liver (and possibly other tissues) after SVR, and generally remains under 'control' unless some unusual circumstance causes to begin replicating at higher levels. (ask Mike Simon about this phenomenon)

So basically all I am really saying is that my perception of many in the mainstream HCV medical community is that they have been very resistant to acknowledge the many studies out there regarding 'persistence', relapse, etc.  I think they often automatically label any late relapse a reinfection, generally without any proof on their part, because their preconception is that the virus is 'eradicated', and a person cannot relapse if they were SVR.  Even though the reports of very late relapse are very few, they must be taken seriously, and understood.  If they are in fact valid, then it only means that the virus goes into 'remission' after SVR, rather than being eradicated.  Much of the research on HCV over the past three or so years has been pointing to this theory, in light of all the findings of viral persistence.

I am not claiming to know the final answers, but am trying to prevent the mainstream HCV community from 'steamrolling' these reports without any 'proof' of their point of view.  Durability of SVR does not automatically equal Eradication, or total cure, in my opinion.
I would LOVE to believe that the virus is eradicated completely on SVR, but I keep reading research studies that say otherwise, and it leads me to ask more questions....rather than circle the wagons and say 'it can't be true!'

I also just want the truth.  Serious studies over the coming years will provide that truth.  I really hope your theories are correct, because I don't like the idea of 'remission' any more than you do.....but if it turns out to be the reality, then we need to understand how it works, and what to be wayy of in our lives.

Thanks for your follow up commentary.  Your points are well taken.

DoubleDose

[returntosender]

I would just like to say that this forum, when it stays on point and doesnt get off on arguments over nonsense, is quite simply the most amazing educational resource and I am in awe of the quality and diversity of the individuals who are contributing here.  

The level of analysis and knowledge is pretty impressive.  I didnt realize how much I have gained in my own knowledge until I met with my primary doc yesterday.  I was able to talk to him about current studies, research, testing protocols, clinical trials and who is conducting them, trends, test results and their implications and much more.  After a while he said "wow I didnt realize how little I know about this subject, what test did you want again?" LOL  This was the guy that I was initially relying on for treating this disease. I now realize that he was a much in the dark as I was.  And compared to a lot of folks here, I am just getting up to speed on a lot of these things.

I am really excited about what happens here and the commitment and time that people spend broadening the knowledge about this disease.  And besides that, it is equally impressive how helpful and supportive people are when things go bad.  I was struck by the genuine concern given to me after my relapse.  Good looks, compassionate and smart too - what a combination!  LOL.  

DD - thanks for continuing to keep us on topic with this important issue.

[jmjm530]

They're talking "reactivation" of virus not reinfection. From everything I've read this is non-existent or rare if we're talking about classical relapse a year or so after SVR, but I'll leave it to others to explain the other point of view.

[aiuta]

What is the immuno-suppressed or immuno-comprised that they are saying is a risk factor for re-infection.  Can you give some examples of situations or drugs that could induce this condition please?  Thanks.  Aiuta

[jmjm530]

I'd also like to agree that by the sheer repetition alone of this topic over the past month or so -- someone relatively new here could very well start to assume that much of this speculation is established fact, possibly causing unnecessary worry and anxiety. And while no one is suggesting viral "reactivation" after SVR is common, the point that it is extremelyh rare -- if happening at all -- seems to be getting lost.

-- Jim

[jmjm530]

Just to let you kmow I pretty much agree with most of your points. Also, a parallel discussion is going on below in the thread titled "Restarting treatment earlier. Is it a mistake?"

Changing the subject, how are things going with you? I assume you're still blinded but wondered what week you're currently in and if you have any 'indications' of what your VL might be. Also, how's the skin doing now?

Hope this finds you relatively well.


-- Jim

[mremeet]

DD quote:

[cuteus]

but there is such a research already.  Yrs ago, girlwithepc,  a pt at the Manhattan ctr was asked to participate in such a research.  They collected blood from chronically infected, spontaneous clearers, and tx induced SVRs.  There has been a few places collecting similar samples.  What they are doing with them at the moment, has not been disclosed. Just because we don't know who is doing what, it does not mean no one is doing anything.

[Myown]

Hey ya know what,,,proof in the pudding,,they're leaving the geno 2's out on the back porch because not enough of us, so if they don't want to study my geno where they can make only little bit of cash,,you know darn well they haven't any interest in people who spontaneously clear and its ashame. Maybe in your search, you will spark an interest in a doctor thats willing. hope so.

[DoubleDose]

You really hit the nail on the head with that last comment!!!!!

DD

[Myown]

I think some of the answers may be found if doctors/researchers begin to study what is the common denominator between all those who clear spontaneously without having to undergo tx at all.

Has any doctor ever taken tests of these people to see what they have in common? From what I've read on forum, these people are told by the doctors that they are lucky and then they are sent home, never to be seen again.

It can't be that they are super duper healthy people either in order to clear on their own. One person on forum mentioned that she is a drug addict and stuck the needle in her arm after her boyfriend, knowing he had hep c,,,yet this person cleared the virus spontaneously. A heroine addicts immune system you would think would not be quite up to par, so go figure? I'm happy for her, but its a mystery and a mystery that doesn't seem to be getting enough attention yet.

I don't know if I am making my point, but we are wondering why someone may become HCV active again after immuno-suppressive therapy and the answer is no where found,,so I say don't send the spontaneous svr home so quick,,,the doctors should be giving them every blood test under the sun and find 'what they all have in common'. Maybe answers to other questions will be found while looking. Maybe(?) because there isn't any money to be made in studying these people,,they don't need drugs.

[mremeet]

Hey mike, wanted to ask you a question about your statement: "The reactivation of HCV (or relapse, if you will) that I have seen is often the result of the introduction of steroids - either bolus intravenous injections or commencement of steroid therapy."

I've seen you refer to this before and was wondering where you read this? I've only seen a study that was conducted on HCV+ chronically infected patients that were given a 1 month prednisone taper (starting at 60mg I think?), and they were found to have a significantly higher viral load during their taper dosing. But VL's returned to baseline levels shortly after concluding their steroid treatment. Then, after completing the steroid treatment, SOC therapy was started. If memory serves, there were no significant difference in response/SVR rates when compared to those who did not receive prednisone dosing prior to the commencement of SOC.

Personally I'm still skeptical about the so called viral persistence/occult infection. There are literally thousands and thousands of drug induced and naturally cleared SVR patients who have been clear for many years now (clear according to "normal" sensitive PCR's that is). Drug induced SVR's have been around for over ten years now and of course naturally cleared SVR's have been around for many decades. Out of this large body of people, surely there has been a fairly decent sized subset amongst them that has experienced very significant challenges to their immune systems. By that I mean people who were coinfected with HIV, and/or who have other similar adjunct life threatening illnesses (cancer, pneumonia (often associated with the very elderly), chronic viral/bacterial infections etc etc), and/or who have taken extensive immunosuppressive (i.e. steroid) therapy for a variety of reasons (i.e. to control various automimmune conditions and/or for rejection management of transplants etc). And since this sizeable subset of long term HCV "SVR-ed" immunocompromised people have existed for some time now, wouldn't we expect to see a a very noticeable/distinct HCV relapse rate amonst these people *IF* the virus were persistent and viable as suggested by these recent "occult infection" studies?

Another reason I'm skeptical is because they assert the virus is distinctly present (albeit at very low levels), intact, viable, and found insitu within the liver itself (and elsewhere). And since an SVR patient is not immune to HCV and *can* be reinfected...how can this be? If nearly all these SVR's have truly viable HCV virii within their bodies, how does this assertion segue/marry up with the notion that HCV SVR's can be reinfected and are never immune after clearance? By that I mean if the virus is there and viable, it obviously only takes a very small amount of HCV to infect you in the first place (technically only one viable virus can do it), and an SVR can be reinfected and has no immunity, then why don't these people experience a full on reinfection in short order? It doesn't seem to make much sense, at least on the surface to this layman.

Lastly, I think the notion of the very small percentage of SVR patients "relapsing", and that observance lending credence to the idea the virus tuly is persistent has to be carefully considered for the following reasons:

1. I suspect a good percentage of the so called long term SVR "relapsers" are in fact reinfections, and NOT a "resurgence" of an occult viral infection. Lets face it, a very significant percentage (perhaps even the majority) of those who have/had HCV were/are IV drug users. And the drug use relapse rate (not viral relapse rate) for those chronically addicted is quite high. It's very common for those with an IV drug problem (especially heroin, which is incredibly addictive) to struggle with their addiction on and off, while periodically (drug) relapsing at various points throughout their lives. And when reinfected then show up at their doctor's office for retreatment and when questioned deny their drug use out of the normal social reasons associated with stigma/shame/embarrassment. Unless the doctor knows for a fact the patient has been using, all he/she can do is simply write down "viral relapse" instead of "reinfection".

Secondly, aside from reinfections from illicit drug abuse, there must also be a small number who have simply become reinfected through some other environmental mode. Perhaps even via a mode similar to how they were initially infected in the first place. I'm sure there are some who unknowingly/unwittingly engage in risky behavior (not associated with sex or drug use) which significantly enhances their chances of reinfection. Also, simply being out amongst the general population puts one at risk. How many HCV+ people have we met who have no known risk factors and sincerely/legitimately have no idea how they contracted the disease? As with their initial infection, a continuing risk of reinfection exists by simply being present on the earth and amongst the general population (and all people, SVR and otherwise, are continuallly subjected to this risk factor). Reinfection may happen for only a small percentage of people, but the fact remains it can and does occur. These people too might end up being incorrectly classified as "relapsers", when in fact they were actually reinfected.

2. There must also be a small number of long term "relapsed SVR's" who never truly were clear of the virus in the first place. By that I mean either their initial post treatment/natural clearance PCR tests were false negatives, or their VL's were present but just below the detectable range used, and/or the lab and/or phleb techs screwed up/misidentified/mishandled/etc their blood samples. It's unlikely for this to happen more than once consecutively (i.e. more than once in a sequence of PCR tests over a prolonged period of time), but it can and I'm sure does happen once in a blue moon within a pool of thousands of people. I've seen some serious goofs in my own bloodwork and/or have witnessed some really incompetent techs on occasion. Mixing up phleb vials, or writing down incorrect patient data and/or not handling the sample(s) properly (freezing, centrifuging etc) or not sending them out promptly to prevent degradation etc. And  that's just what I can see when their taking my blood, I know human error doesn't end at the lab itself either (which we cannot see).

So considering these examples, combined I think they could easily account for the very small group amongst long term SVR's that are called/considered "relapsers". Honestly, especially considering number 1 ascribed above, I'm surprised how few observed "relapsers" there actually are. I'd expect to see more really, again especially considering (a) how often hardcore IV drug users fall off the wagon throughout their lives and (b) how common drug use denial is out of shame/stigma etc.