Restarting treatment earlier. Is it a mistake?

[Sally01]

Hi, I received my first UND in July and then my Peg/riba treatment was interupted off and on the next few months due to illness.  I am still receiving treatment for an opportunistic lung infection which is apparently very stuborn.  I am post transplant also so my immune system was pretty low.  Also I worked in a hospital in a highly infectious area.  Won't do that again.   Anyway I have had no treatment for the HCV since Sept.  My November VL came back UND.  I was thrilled but a little surprised
      I asked my doctors if I could start the Peg/riba again so as not to loose this opportunity to acheive SVR but they all seem to put the question off or refer it to another doctor for approval.  Final say was to come from the transplant team in Miami.  They don't see me until Dec 12th and was told to wait until I was seen.  My nurse co-ordinator is out ill and no one is responding to my plea for more immediate help.
   I feel better than I have in months.  No doctor has givin me a reason for any kind of interaction with the ribasome I am taking.  Last Wed I had blood drawn and my liver enymes had elevated from 14 to the 50's.  Scared me.  I took the peg and riba on Thanksgiving on my own.  Seemed bad to wait for appointments when the meds are in the fridge.  After about 6 hours I had a bad flu-like reaction but the next day I was better and am continuing to do well.
    Do you think I messed things up> I am planning to take it again on Thursday.  By the time my Dec 12th appointment rolls around I will have taken it 3 weeks. If I feel ok which uspectI will should I tell the

[sfbaygirl]

Of course I am slow getting ready, duh! I have to stop by and see m y daughter and baby at 11 and off to the airport. See you soon!

[Kalio1]

I think the risk at the dentist is from improper care and sterilization of instruments. Procedures that involve "bony fragments" are riskier like tooth procedures or heart surgery. Dentists and heart surgeons have higher incidence of HCV than other specialties. The risk of contracting HCV through these procedures is far greater for the doctor than the patient I would think. The key problem as I see it with HCV is the fact that can live for 4 days (I've read up to 10 days in certain conditions)on any surface is significant. It is very durable virus. This is why clinical settings seem a logical mode of transmission due to the sheer numbers of people who pass through them. In these settings the poorest paid personnel are responsible for these tasks.





Hey I wanted to say have a safe trip!

[sfbaygirl]

Why would dental procedures be risky? As I said earlier, my x was told to take antibotics every time he had a dental procedure done after a heart valve infection. This was years ago, but what is it that stirs up virus/bacteria while doing dental work? Is it hiding in our teeth? How would these procedures compromise our immune system, unless it was already.

[jmjm530]

I think the reference is to some of the shorter course studies for geno 1's that suggest 24 weeks of treatment is as effective as 48 weeks if two conditions are present -- RVR and low pre-tx viral load. The 89% SVR figure cited seems consistent with other shorter course studies such as the one the European Union? based their shorter course recommendation on.

I do agree, however, on the pitfalls of relying on "second hand" reporting. But sometimes even worse is relying on badly written and therefore potentially misleading abstracts. Fortunately, unlike myself and most here, you have easy access to the full-text.

I've spent a pretty penny myself during tx for full-text when
the articles I found related to important tx decisions. I  have urged others to do the same and not rely on abstracts which is mostly what gets posted here.

All the best,

-- Jim

[Hepatitis Researcher]

Thank you, there is some variability here, but overall, considering the reinfection issue, the stability of SVR is quite remarkable. This issue is evenmore important if one considers the need to treat some of the ongoing side effects after tx and the question to what extent can we be "mildy immunosupressive" and not fear relapse.

Here is something, citing a Jensen study, right after the stability chapter in your ref. that puzzles me and makes me think of the reliability of some of this "second hand" reporting:

Quote: "
In this study of patients treated with Pegasys plus Copegus, data from 729 genotype 1 patients with week 4 results were available and analyzed. Of these, 146 patients had an RVR

[jmjm530]

Anecdotally, Dr. Ben Cecil, a hepatologist who is publically forthcoming with his practice data states:

"I have several hundred patients with sustained viral response and 2-3 have relapsed 12 months after their last injection. No one has relapsed later than one year, and I have been doing this for almost 7 years now."
http://tinyurl.com/y6umdw

I have heard similar anecdotal stories on SVR durability from others posting what their doctors told them.

[jmjm530]

Here's a reference to a promising five-year study that cites SVR data between 99.2 per cent and I believe 100 per cent for the combo group. Also discusses the reinfection issue:
http://www.hcvadvocate.org/news/newsLetter/2006/advocate0106.html

Lastly, the study I think I was looking for that goes ten years out  which states in part:

"...All but one patient who achieved SVR (> 99%) still had undetectable HCV viral load after a mean follow-up period of 2.3 years (range 0.3-10.3). The authors concluded that advances in hepatitis C therapy have produced higher sustained response rates in the clinical setting. They also suggested that since this response appears durable, medium and long-term follow-up of patients with SVR is

[jmjm530]

Here's one five-year study:
http://www.natap.org/2004/AASLD/aasld_20.htm

This one goes 9.18 years out:
http://bmc.ub.uni-potsdam.de/1471-2334-5-27/

Here is a compliation of articles on a number of SVR durability studies: http://www.natap.org/2004/HCV/083004_06.htm

I believe there is also another recent study that mentions 10 years which I will post if I can find again.

Also, Dr. Donald Jensen specifically speaks of studies suggesting the durability of SVR "5-10" years out in his video "Doc Eye for the Hep Guy" at the Clinical Options Website. You can fast-forward to the 8 minute mark for this portion of the presentation. I'm sure an email to Jensen from another doctor should produce the studies he's referring to.

Jensen mentions a figure 96% figure which seems to me quite conservative based on both some of the five years studies and what I have read anecdotally from doctors in the field. Perhaps the lower mark -- I've heard the close to 100% figure -- may be due to older studies  initially using less sensitive testing, possibly monotherapy, fixed dose riba, and even HIV co-infection being mixed in -- or the reinfection issue already addressed. Just speculation on my part as I haven't read the full-text, only abstracts. Hope this is helpful.

All the best,

-- Jim

[jmjm530]

No, Jensen did use Pegasys but I'm almost certain the study used by the European Union? was a Peg Intron study but that's for another day.

[jmjm530]

Here's a Ferenci study that has a 77% success rate for short course but it uses Pegasys not Peg Intron as I believe the Jensen study might have. In a similar fashion, studies with selected geno 2's and 3's using Peg Intron have shown similar SVR rates for 12 versus 24 weeks while the Pegasys studies used 16 weeks versus 24.

http://www.natap.org/2006/EASL/EASL_03.htm

Apologies for the fragmented posting but unfortunately I've never saved these studies in an organized manner so I have to look them up from memory.

[jmjm530]

Not sure if this is full-text but a better idea of what the Jensen study stated:
http://www.natap.org/2005/AASLD/aasld_55.htm

There's also that European Union? directive I can't seem to find but will post later if found.

[Hepatitis Researcher]

Sorry not much time today.
Jim , could you possibly supply a list of actual literature citations - papers- that deal with the isuue of durability after SVR - up to 10 years.? The ones that I have so far look good - but not that good - as you mentioned at several occasions.

Obviously, the point made so convincingly by another member a few threads up - that reinfection from the outside needs to be considered and figured in- must be searched for carefully in the methods section of these papers...
How come Peter Ferenci ( with whom I worked in Vienna BTW, long time ago) did not find anyone with increased HCV RNA considering that some of those should have been iv drug users, with all that risk of reinfection..  A few numbers and methods here need careful investigation.

[jmjm530]

DD: I am not saying the SVR is not durable...it has surely proven to be pretty much a 99%+ solution...(But the virus may be) in remission... And if this is true... then we would be prudent in asking some serious questions, and being cautious about certain medications (and procedures).
---------------------------------------------
For discussions sake I'll accept the "99%+" solution. I figure at my age (almost 60) I have way more than a 1 per cent chance of succuming to more serious conditions than a theoretical relapse of the virus, and I imagine the same with you too. So, on a personal level then -- and please take this as a question from a friend -- why the worry and energy expense about something with less than a one per cent chance of happening? As to why I am concerned about the dental procdure, I think I've already categorized that thought process as a bit irrational, especially beyond the one year mark where the chance of relapse apparently falls from around one per cent to close to zero. So that's what I might do, wait another three months (the one year mark) since the dental implant is elective. This doesn't mean I undervalue research into this subject. Just don't think worrying about the durability of SVR in terms of medications and medical procedures is very rational.

Be well,

-- Jim

[DoubleDose]

Your own caution about the dental surgery highlights your ambivalence about eradication, to some extent.  Hey, we are all nervous about this issue...how could we not be, in light of all the recent research on persistent virus, findings of tissue based virus, relapsing SVR's on immuno therapy, etc.  We can all hold up the garlic or the cross to the vampire and say 'its durable, its durable' etc. until the cows come home....but down deep we are all nervous about this issue.  Your own concerns about medical procedures bring this home pretty clearly.  
I am not saying the SVR is not durable...it has surely proven to be pretty much a 99%+ solution.  What I am saying is: the virus may not be eradicated.  It may be in remission.  And if this is true, as most researchers are now implying, if not saying outright, then we would be prudent in asking some serious questions, and being cautious about certain medications...until we know much more.  Jim, I have to believe that if there are just TWO relapsers, who were truly SVR on PCR for multiple years, then it is cause for looking much more closely at what SVR really implies.  

DoubleDose

[jmjm530]

Cuteus, you do understand we are in agreement here? I only raised the issue of RTSs dental work because he did, and because others have been suggesting (like DD and HR) that this type of event could potentially cause a "reactivation". I say where is the "meat", the studies, the data that supports this. Still, still, on a personal level I admit to a very small amount of anxiety regarding my impending dental work based on these discussions, even though my "rational" mind (and my doctors) don't see any issues. Since I'm going to have some dental work done sooner or later, I think a reasonable compromise might be to wait another three months until I'm one year SVR. Then, if I relapse, I will become the rarity that  some researcher will write about :)

-- Jim

[cuteus]

if we are going to assign post tx dental work a place in RTS's relapse, then how is it that we are not acknowledging the role of surgery in other post tx members and their SVRs.  We can't address post tx stress as a factor, but ignore those of us who underwent extensive dental work that included root canals, extractions, bridge prep and mounting, surgery for the arm or the hand, celebration with alcoholic beverages, etc, all BEFORE the year was up post tx.  You can't focus in one and not the other.  If I am still negative, after all these procedures and medications and drinks, prior to my first yr post tx, and I am sure I am not the only one, how is it that we are placing so much value in the dental work being a factor in rts' relapse? it makes no sense.  He is one person and I am one person.  50/50. hardly able to make a connection one way or the other.;

[jmjm530]

Hopefully, I clarified my statment in C25 above. In any event I think we are now in agreement on both the definition of "persistent" virus and "reactivation". It was the reactivation issue I was addressing in terms of immuno-suppresive type events like surgery and how they may or may not affect SVR. But again, so that we're clear, I'm defining "reactivation" as a change from HCV RNA negative to HCV RNA positive in serum after SVR.

Assuming we both agree on that definition, what study(s) are you basing your following statement on:

"No, what I am talking about with the virus coming back after years of SVR (in the immunosuppressed cases), has everything to do with 'persistent HCV after SVR'. This persistent virus after SVR may be the 'remission' form of the virus, which is now being held in check by the immune system. If an extreme shock to the immune system takes place, thus effectively shutting it down for a period of time, the virus might then re-activate, and begin to reproduce beyond the control of the immune system, thus being 'reactivated' and becoming the chronic, active HCV infection that we all are very familiar with."

To the best of my knowledge there have been only one or two cocumented cases of this type of "reactivation" and it seems that you really can't draw conclusions from one or two isolated cases.
That compared to several studies -- over 1000 patients -- that suggest SVR is durable around 99 per cent over a 5-10 year period and closer to 100 per cent after being non-detectible for the one year mark.

All the best,

-- Jim

[DoubleDose]

Jim, you said:
As to HCV coming back after "some years" I only know of one or two documented cases, so one really has to be suspicious of what one hears in this regard. What double dose and others are talking about is altogether different. They're talking about "persistent" virus meaning it's non-detectible in your blood but seemingly present in tissues and the lymphatic system. So far there are proven clinical consequences for the persistent virus and for all we know it may be totally benign. Time will tell.


My reply:

No, what I am talking about with the virus coming back after years of SVR (in the immunosuppressed cases), has everything to do with 'persistent HCV after SVR'.  This persistent virus after SVR may be the 'remission' form of the virus, which is now being held in check by the immune system.  If an extreme shock to the immune system takes place, thus effectively shutting it down for a period of time, the virus might then re-activate, and begin to reproduce beyond the control of the immune system, thus being 'reactivated' and becoming the chronic, active HCV infection that we all are very familiar with.

My conjecture is that the 'persistent virus' is exactly what causes those cases of rare relapse. Similarly, the people who have 'spontaneously cleared' the HCV virus, by the way, also seem to have the same evidence of 'persistent HCV' in their bodies in various tissues, etc. (and similar symptoms) These people would also be at risk for a 'reactivation' of the chronic infection if they became immuno-compromised, but again, since they cleared it initially years before, they might just clear it again.  Those who got their SVR from combo medications would probably not be so lucky.

I just wanted to clarify my prior comments.

DoubleDose

[jmjm530]

Child:Jim, I am not on the right path here? having "persistant"
virus in tissues and such after being non-detectable then comes back right? 3- 6 mo right?

If something comes along like surgery or such would that not reactivate the virus,even if undec. for a year or so, if it is like hiding somewhere?
-------------------------------------------------------
That's the theory but IMO it has to be balanced by the incredible sparcity of relapses after six months -- and especially one year post treatment. If no one is really relapsing -- as defined as detectible HCV RNA in serum -- then where is the reactivation? I believe there are one or two documented cases but IMO that's too small a number to draw firm conclusions from.

-- Jim

[jmjm530]

The reason for the second part of the question is that I assume a certain proportion of SVRs have dental work in the year following treatment and yet we all know the HCV durability studies. I'm not trying to answer my own question -- or perhaps I am :) -- but simply concerned because of RTSs relapse with a dental procedure mentioned as a possible cause. So on one hand I don't believe there's a problem, but on the other I'd like as much info as possible. I understand the theory behind reactivation, but if indeed documented cases are either non-existent or rare, doesn't that shoot holes in the theory?

[jmjm530]

No fear of reinfection, the question only related to "reactivation" of virus due to what you term reduction in immune effectiveness. Specfically, would you recommend the surgery now (I'm 9 months non-detectible since stopping the treatment drugs) or would you wait until after the one year mark. Taking any type of interferon drug prophalacitvely is not an option I would even consider. The second part of that question is have you ever heard of an actual relapse after SVR for something like a dental procedure or simple operation. Thanks.

-- Jim

[jmjm530]

Sometimes being cautious isn't being logical. Logically, I don't think I have anything to worry about with dental work, whatever, as studies suggest the durability of SVR. It just seems that the durability climbs from around 98-99% to close to 100% as you become non-detectible one year post treatment. As to HCV coming back after "some years" I only know of one or two documented cases, so one really has to be suspicious of what one hears in this regard. What double dose and others are talking about is altogether different. They're talking about "persistent" virus meaning it's non-detectible in your blood but seemingly present in tissues and the lymphatic system. So far there are proven clinical consequences for the persistent virus and for all we know it may be totally benign. Time will tell.

[Hepatitis Researcher]

The tooth implant or any surgery exerts some stress on the body with temporary reduction in immune effectiveness.
In the future we might have temporary no sides HCV shielding drugs for such occasions. You could even now use a 20% Pagasys dose in and around that time to be really safe.

But if you fear reinfection from an external source - your chances should be about the same as for anyone in these procedures. If no vaccine will be found, there will be 20 Million HCV cases in the USA by 2018 or so....
Chances are obviously still quite small and it probably is better not to be overrestrictive- do what really needs to be done, but dont tatoo  " I beat HCV"....

[jmjm530]

My concern with the dental procedure is not reinfection, but reactivation as suggested by RTSs thread where he relapsed somewhere between the 3 and 6 month post treatment point and mentioned his dental work as a possible cause.