hepatitisresearcher

[spcecst2]

Your opinion please? Lets say a patient went thru treatment (1b) pegasys/copegus 180/1200 for 48 weeks, starting VL was 10 mil, middle aged male, slight liver damage, still detectable at 600 week 12, clear week 16 (less than 50), relapsed, waited 3 months and started treatment over, VL 500,000, double dose pegasys 4 weeks, 1400 copegus, no VL detected at week 4 using heptimax, did shot every five days from week 4 thru week 12, did 1600 copegus for month and half, waited full seven days at week 12 and got negative heptimax, doing 180/1200 rest of treatment, ast/alt normal at week 12, does this person have the same chance with RVR statistics (as high as 85% SVR) with 48 weeks, or are those RVR statistics only good for someone who does treatment the first time using the SOC? I hope you can understand what I’m asking here?

[mremeet]

DDquote: "I make a few comments, echoing what Willing and Mike had stated..."

Mike and willing echoed your sentiments that HCV is passed on by SVR's to uninfected people via casual contact? Sorry but I didn't see them state nor infer that. And I seriously doubt they believe that either, although I'll let them speak for themselves.

DDquote: "And, by the way, Castillo is NOT the only researcher who has discovered replicating virus after SVR."

Sure, that's why I said "et al" above. You know what et al means, right? And it has nothing to do with hungry cannibals, either.

DDquote: "I am not having a hypochondriacal fit, or anything of the sort.  Merely pointing out my particular observations and opinions."

I'm not saying you are having a hypochondriacal fit. But your belief that you're passing on the HCV virus (or symptoms) to those around you via casual contact, especially now that you're SVR, frankly is hypochondrial-like. I think most well informed and reasonable people would agree. And that's just me pointing out my observations and opinions.

DDquote: " I hope you can live with that"

I can live with it, and I hope you can live with being confronted with plain facts and thoughts that are contrary to your casual contact theory. And also concerning the stalwartness of the viral persistence theory that ties into your casual contact nervosa. Also, I've passed on commenting on many of your posts of this nature in the past. But you voice this theory so frequently that I've just got to say something about it. I mean, why not? This is an open forum, I am allowed to discuss it with you or anyone else for that matter. Like I said before, you're a good person and a nice man. But you being a good person does not immunize your theories from being open to critical debate. Especially when they'e as far out as your pet theory is. Besides, it's good for you to hear it. It might remind you that your worries are overblown and perhaps you'll be brought to understand there is an element of anxiety in your fears. I mean, you remember that really nice guy that had bad BO in highscool, and yet no one told him he had bad BO? Wouldn't it be better for someone to gently tell him? No one was doing mr stinky any favors by being politely silent. C'mon now, huh??!  ;-)

[willing]

it's very appropriate that an HCV forum have such limited memory, in fact it's one of the most endearing aspects of this place as it allows one the joy of rediscovering fundamental  truths on a regular basis! However, I can assure you your warnings about contamination were not forgotten - I think about them every time I'm pipetting, though I can't manage the luxury of separate benches, let alone buildings.

The hypothesis of riba as a facilitator for bystander killing of the residual stealth virions by promoting "loud-mouthed" mutations  is indeed attractive  A fly in in the ointment is that Crotty's "error catastrophe" theory seems to have come under attack, by Pawlotsky's lab among others:

Chevaliez S, Brillet R, Lázaro E, Hézode C, Pawlotsky JM.
Analysis of ribavirin mutagenicity in human hepatitis C virus infection.
J Virol. 2007 Jul;81(14):7732-41. Epub 2007 May 9.
PMID: 17494069

and
Chang KO, George DW.
Interferons and ribavirin effectively inhibit Norwalk virus replication in replicon-bearing cells.
J Virol. 2007 Nov;81(22):12111-8. Epub 2007 Sep 12.
PMID: 17855555

Also I wonder whether the relative size of the population resistant to SOC is a function of the host or of the quasispecies distribution. As I noted above, my interpretation of the success of the gene-expression predictors of SVR outcome is that the prevalence of "stealth" virions may depend more on the host's HLA alleles than on the original viral genome.

BTW, on the subject of testing,  it would be interesting to hear your thoughts on

Kretzschmar E, Chudy M, Nübling CM, Ross RS, Kruse F, Trobisch H.
First case of hepatitis C virus transmission by a red blood cell concentrate after introduction of nucleic acid amplification technique screening in Germany: a comparative study with various assays.
Vox Sang. 2007 May;92(4):297-301.
PMID: 17456153

or
Grabarczyk P, Gronowska A, Brojer E, Letowska M, Radziwon P.
Sequence analysis confirmation of transfusion-transmitted hepatitis C by red blood cells that tested negative by minipool hepatitis C virus nucleic acid testing.
Transfusion. 2007 Jun;47(6):1102-4.
PMID: 17524106

while sensitivity  of tests is important to patients, it's presumably all the more so to those managing the blood supply.

[DoubleDose]

Why, you would have thought that I had put a big MREMEET tag on the subject line of my post!  WOW!  Sensitive, sensitive, sensitive! I make a few comments, echoing what Willing and Mike had stated, and ask a few reasonable questions...and as usual, you jump out of your skin to refute or qualify my statements, and to make personal attacks on my own motivations, etc.  Don't you think you are being a bit overwrought?  I understand completely the issues you pointed out, and always have.  But I also do see the behaviors in the HCV medical community that I pointed out.

  And, by the way, Castillo is NOT the only researcher who has discovered replicating virus after SVR. Far from it.  There have probably been more than eight or nine researchers finding similar viral behaviors after SVR, in recent years.   I am not having a hypochondriacal fit, or anything of the sort.  Merely pointing out my particular observations and opinions.  I hope you can live with that.  That's all we have here, is our opinions.  You are about as much a medical expert as any other person posting on this forum, and by your tendency to attack others who you disagree with, I would say you might benefit FROM some medical expertise!  I am not quite sure what your problem is.

DD

[mremeet]

DDquote: "What I continue to be unclear about is just why the mainstream docs continue to ignore, or even worse mis-interpret the data on viral persistence after SVR."

Can't speak for how most doctors feel about the persistent low level virus schpiel, but my doctor openly acknowledges the Castillo et al findings and does not ignore them. But he does not currently accept them as an irrefutable fact either, he says more study is needed and that by all appearances the vast majority who achieve SVR are cured (and the word "cured" is freely used by many top tier research doctors too). And even if there is a low lying ongoing infection, effectively SVR patients by and large are cured of liver disease (in stark contrast to their condition prior to achieving SVR). Also, assuming there is ongoing low level persistence after achieving SVR, realistically what can be done about it? Nothing that I know about. And more importantly, what should be done about it? Should another phase of antiviral treatment be developed to go for that second tier *deep cleansing* that all us SVR's really need in order to get our health back?

DDqote: "If the non-research oriented medical experts dealing with HCV are unwilling (no pun intended) to acknowledge this phenomenon, then how will we ever really understand true viral behavior..."

By "acknowledge the phenomenon", you mean simply accept this is an irrefutable fact without any further debate or research to help resolve the issue with more clarity and certainty? If so I certainly don't agree with that, and I know that many well educated hepatologists don't either. And also, why would it be so important for "non-research oriented medical experts" to accept this theory as fact? Wouldn't it be more important for research oriented medical experts to take it more seriously and to devote more study to it? Working doctors primarily deal with what treatments/drugs are available today and they also tend to focus on things they have some control and influence over. They also tend to only treat patients who need their care and expertise. SVR's often don't require their care and expertise, at least in regards to the issues associated with an ongoing HCV infection (obviously because they're SVR). So why would it be so important for non-research oriented working level doctors to be so wrapped up into the whole viral persistence debate?

DDquote: "...and find out what the presistent virus might be capable of in those who are long term SVR's?"

You mean like SVR's transmitting the virus to others vis-a-vis casual contact? That pet theory of yours is not accepted within the scientific community at all, and there is no real evidence to prove that's true. Those are the facts.

DDquote: "I also think that many HCV treaters also tend to want to ignore the recent studies, and the concept of a viral 'remission' relating to treatment of HCV."

Really, like who? Certainly not me, nor anyone else I know who is SVR (and is aware of the studies). Although I will admit to experiencing a building feeling of extreme confidence that I'm not going to relapse and I will admit to the onset of boredom pangs with the whole concept that I'm just in remission and I'll relapse at any time. But is there a perfectly rational and scientifically sound reason for me feeling that way? Absolutely there is! SVR is durable, SVR infers histological improvement, SVR often infers resolution of HCV related symptoms, SVR means more LIFE - SVR is fabulous. Furthermore, aren't there also just a few SVR's who literally *need* to believe in the viral persistence theory in order to rationalize and justify certain hypochondrial-like anxieties? I think so, don't you? And you don't even have to be SVR either, in fact you don't even have to have ever been infected with HCV in order to become obsessed about this sort of thing. Just look around on this forum, and you'll see that's true.

RELAX DUDE.  http://youtube.com/watch?v=yjnvSQuv-H4

[motheroffour]

Regarding mutated virus - this was something that the Big U doc my husband visited last week alluded to and implied might be what has happened to my husband during Treatment 1 and possibly now during treatment 2.  Is the only hope for someone with potential mutated virus to wait for new drugs on the market if there are no new studies on the horizon?  H has used PegIntron now for both treatments, Big U doc suggested clearing out his system for 2 months and trying Pegasys?  What ever happened to the side by side study of Peg vs. Intron and did that study only deal with treatment naieve patients - I'm not finding any reference in the threads....also wondering about changing from PegIntron to Pegasys mid-stream with no 2 month cleansing....thoughts anyone.

[Hepatitis Researcher]

willing:
A related topic in interpreting these results is the false positive rate of TMA tests

Yes, extremely important in this context. Thats why i have pointed 3 times already at the false positivity problem of theTMA and described the incredible cumbersome means to avoid false positives using  the supersensitive PCR test  (below 2 iU) at Labcorp/NGI. It is forgotten in  a few days.

You hint, quite correctly IMO, at the fact that a tiny part of the preexisting quasispecies might not respond to treatment, because it has a priori evaded the cytotoxic CD-8 T cell response by shedding its class 1 effective CTL epitopes, as a means to evade.
Upon treatment, the main HCV quasispecies portion drops rapidly - RVR- but the small unaffected portions stays almost the same. Hence the true VL curve hits, after initial rapid decline, a deep plateau, when it encounters the non susceptible portion.
There are of course ten shades of gray in between this black and white picture. But the CTL epitope evasion theory has the best chance to reflect the actual reality behind all these phenoma.

The real important effect of riba, IMO, is that it might drive the viral proteome (sum of all proteins) into a state, where

new effective  HCV CTL epitopes are de novo ( not existing before treatment) created by hypermutation.

By the collateral effect of activated ( by hepatocytes  carrying these new reactive epitopes)  CTLs on other  nearby infected  " pseudoclean=no CTL epitopes displayed)" hepatocytes, by " noncytolytic" clearance, due to intense local cytokine production by the positively TCR engaged  CTLs,

broad clearance/antiviral effectiveness is now provided.