hepatitisresearcher

[glucklich]

On the NAy News on Vx950 thread, oyu wrote

Not only would Protease +SOC for clear nonresponders not permanently eliminate the virus but something much worse will likely happen ( to quote as mremeet has properly pointed out some hundred posts ago:  " you will be saddled forever with resistance mutations against this treatment component").: This archived resistance mutations against telaprevir would make it impossible to clear the virus at that important future moment  when finally the next chance to treat with an inhibitor combo like Protease + Polymerase +maybe Nitazoxanide will become available that MIGHT, JUST MIGHT give a decent percentage chance to clear despite the preexisting IFN resistance.

chilling for those who failed.
Are there any ideas out there about what the 'right " thing to do immediately after treatment while the VL is sill very low and any ideas for the next step other than extending treatment somehow.

[merryBe]

just to be clear here, are we talking House or Doogie Houser??

[scratchinghead]

?

[glucklich]

TG I had a plan which is to follow someone far greater than I

[Lady Lauri]

  And stayed at a holiday Inn express ??????

                                                                        LOL

[scratchinghead]

I googled Tyler, Texas maps and Tyler is about 2 hours from Dallas/ForWorth area. Those are big cities with proabably compentent GIs and Hepatologists.

Also, talk to the GI appointment people about an appointment that is closer to today. I got into my clinic sooner due to a "cancellation appointment". Tell work you have an emgergency dental appointment, whatever.

Genotype 2 is the genotype of choice in terms of cure rates. I'm thinking the numbers are 80%-90%.

I am not a doctor I just play one on TV.

[glucklich]

just booted Pr 3 trial. Arm B
VL  
week - 0 17,000,000
week -1 300
week -2 UND
week - 4 DET
week - 8 UND
week - 12 DET
week - 16 DET
week -20 60
week 24         250

less than  week off SOC meds


Any ideas or is it still :?:


So the official next step is to wait until additional drugs are approved that might be more powerful/less toxic and can be combined to prevent resistance development against the combos components

[justvlm]

Wow, this has become information over-load for me.  I'm a pretty smart cookie (or at least thought I was).  I've read as many threads as I could and wondering if I could get some thoughts regarding me current stage of unknown.  I was dx 3 weeks ago during a routine check-up.  My primary is less than I would call o.k. (sadly a poor replacement for my doc of 20+ years).  None-the-less, he referred me to a GI (will see her in January).  All I got from him is type 2b, iron on the high side so avoid red meat (didn't think I ate that much red meat so now do I eat none?)  Unfortunately, that's it.  I have ask the records dept for a copy of the blood tests, but can't get a return call from them.  GRRRRR.  Anyway - point of this - I'd like to be as informed as possible when I see the GI and ask the needed questions regarding tx and waiting, but that would appear that is purely bases on her experience and how up on trials she is.  I would like to do these "shoulda, coulda, wouldas" things before saying "dang-it - wished I'd ask".   So I'm hoping for any suggestions, tips, that any can give me the primer version of where I should go with my tx options, get a bx before the Jan appt, any other help will be so very appreciated.
BTW, I don't believe I have much access to teaching hospitals, I live in Tyler, Tx and working at my 8-5 is of utmost importance.  

[Hepatitis Researcher]

I was aware that your questions was not answered. If your VL after treatment is still very low ( how low at EOT?) and you do not want to extend the IFN/riba treatment, there is at this point in time no meaningful way to keep it low. Even if Telaprevir would be available right now, you would need to combine it with the ifn/riba combo to have a decent chance. I do not know how your VL development under treatment was -"partial responder"? but the rule of thumb is that if you responded once, you can respond again, and a bit more if more IFN (" double dose") or if the eradication/hypermutation/ epitope representation is driven for a longer time " extended treatment". Always only percentage chance changes, no certainty, a new game of roulette with better odds.And the addition of Telaprevir would clearly improve these odds by an estimated factor of 1.5.

You can alternatively try to slow down or reverse fibrosis progression by a series of proper liver protective and stellate cell transformation halting measures. All of these are only experimental at this time and might forever be, since no large trial will be ever conducted to evaluate the effectiveness  of a smart super antifibrotic cocktail, since  firstly, nobody would want to pay for that and secondly they could never agree which mix of measures should be tried.
I can give you just one example ; How effective as such would it be to just maximally reduce metabolic AND intestinal bacteria caused inflammatory stress to the liver ( by an appropriate diet and proinflammatory stress liver stress reduction by improving prebiotic/probiotic conditions in the intestines (eg reduce LPS influx to the liver, a highly proinflammatory/fibrosis inducing event)) A large trial aimed to influence just these two pathophysiological  profibrotic components could find a dramatic reduction in fibrosis progression or only a marginal effect. We do not know the magnitude of such component effects, certainly not in humans, while for many of these "antifibrotic effects" animal experiments are available. For the layperson or even a practicing physician, a much more thorough understanding of all the known mechanisms would be necessary to even get a good feel for the likelihood of such component approaches to reduce fibrosis progression, including awareness and in depth digestion of all the experimental work and the publications that mankind has produced in that regard.
Many contributions to these questions have only been presented as posters and abstracts on meetings like the AASLD and are, with minute exceptions, forever forgotten  and lost in the bowels of abstract books that contain thousands of these pieces of important specific wisdom/experimental insights just  too numerous to be properly recognized, collected and taken into account when an "opinion" is formed on what might work or not.

So the official next step is to wait until additional drugs are approved that might be more powerful/less toxic and can be combined to prevent resistance development against the combos components. This will lead to a further improved percentage of SVRs, slowly improving for SOC naive treaters, always with a lagging of SOC nonresponders in term of SVR rates achievable. And before a treatment modality is approved by the FDA, it is to be considered experimental and insurance will not pay for it. And off label use of drugs like Alinia as addition to SOC is burdened with the risk that the hopeful extrapolations from current data are incorrect and the need to find a specialist that will prescribe it to you and assume responsisibility and knows enough about it to even consider that approach and further the need to pay for the drug yourself.And moreover, your specific treatment/response history has to be carefully examined by a specialist that understands the meaning of the latest data to gauge if  such addditions hold a decent chance for success.

[FlGuy]

My first tx was partly mysterious.  First pcr was week 12, which was und.  And, riba was not weight-based, peg was.  Could make a poster of it 'How Not to Tx'.

[glucklich]

does anyone have an answer to my question?

Are there any ideas out there about what the 'right " thing to do immediately after treatment while the VL is sill very low and any ideas for the next step other than extending treatment somehow.

[alagirl]

Trust me, there still are some rather "Deliverance" looking areas (and people) around the South.  I will have to say though, that people in the South are some of the friendliest people around most of the time.

[alagirl]

My doc uses the Taqman down to 10 IU/ml - I made certain of that because if he didn't use a sensitive enough test I was going to insist that we use another one.  My liver doc is actually in Huntsville, which isn't small.  It's a fairly tech oriented city.  He is extremely adamant about using his lab for all viral load pulls (it's not really his lab, the lab is run by a different company but they are right there in a room at the office where my HCV doc practices and he's approved the orders for all of the testing in advance).

But the lab that initially did my viral load and genotype testing is at one of the hospitals here where I live and they sent it to a lab in Birmingham that was just absolutely awful with their turn around.

[jmjm530]

Ala:  This is an area where people still say of medical issues like diabetes for instance, "Mama's got the sugar real bad."
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Yes, I did see "Deliverance" and for many years subsequent I made it a point only to fly over the South :)

[alagirl]

I really like the doctors who do that for their patients, recycle meds I mean.  My shrink and I do that.  I give her any medication I can't use.  Because particularly if I try a psychotropic med that just doesn't work for me I may have almost an entire bottle left that I paid only an insurance copay for, but which if paid out of pocket would be prohibitively expensive.  So I give it to her.  She's able to use those meds as samples for her patients who have more difficulty financially and I'm always happy to see a prescription not going to waste particularly given the costs of some of these meds when you don't have insurance.  I think my lexpro and especially my topamax (I take topamax as a prophylaxis for migraines) are both very expensive.  She'll even take my meds that aren't necessarily psychotropic in nature.  In this small town where I live sometimes doctors wear many hats and end up having to address ancillary health care concerns with their patients.  Many of the patients here are also not very medically sophisticated, so that makes this particularly true.  To them, a doctor is a doctor is a doctor and any doc having a shot at them may be the only one they tell about a particular problem so if that doctor doesn't treat it in some fashion it may not happen.  People with more complex issues that require a certain amount of case management are frequently very confused as to what each doctor is supposed to be doing for them.  This is an area where people still say of medical issues like diabetes for instance, "Mama's got the sugar real bad."  Sometimes they might get a little closer and actually call it, "sugar diabetes," but you get the point.  

[jmjm530]

You probably already mentioned it, but what test did you use and what was its sensitivity? Something tells me it went down to 10 IU/ml -- which is good -- but I might be mixing that with someone else. But yes, a four day turnaround is excellent. Maybe the small town labs just count the virus by hand instead of wasting time shipping it off to the labs :)

[alagirl]

Certainly getting faster PCR results is a helpful adjunct to personalized treatment
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I was very pleasantly surprised to find that my doc's office does the PCR results so quickly.  I went in on Thursday (of last week, not this past week) for my 4 week draw and the following Monday when I came in to see the doctor he had my viral load back.  I'd expected it to take much longer since my first viral load and genotyping was that nightmare three or four week ordeal with the lab here in town that delayed my treatment onset.  

[jmjm530]

Well worth the bucks IMO. But you'll be surprised what can get through the insurance process if your doc is willing to go to bat for you and says exactly the right things to the insurance company. Few bother or even know cause it's a real hassle. I got plenty of xtra drugs -- Procrit, Peg and Riba -- for my double dose, high riba antics, from my tx doc who had a big stash as some hepatologists do who are affilitated with larger, teaching hospitals. I also turned back more than a month of Peg -- and two months of Procrit -- after tx so he could recycle for other patients. If you had started treating then, the Procrit could have been yours :)

[alagirl]

Yeah.  The trouble is, of course, that to get the insurance companies to sign off on a large amount of procrit (such as 40,000 units or more per week) you have to show the need for the increased dose.  I wonder if you could even get an insurance company to sign off on paying for the procrit for the purposes of pre-dosing when they see it as a rescue drug.  I'm not certain what a month's worth would cost at that level if you went off insurance to buy it.  I know that when I first was increasing my epogen I thought I was going to have to pay out of pocket once so I priced it and I think it wasn't too bad due to being the generic, maybe $50 I want to say? however, that was at a much smaller strength per vial.  Wonder what the uninsured cost is for epogen in the larger strengths.

[jmjm530]

I don't think in your case pre-dosing riba would have made sense, but pre-dosing Procrit (4-6 weeks prior to tx ) might have. Coulda, shoulda, woulda :)

[jmjm530]

Curious, what was your viral response the first time around, and what was your dosing?
I didn't pre-dose -- didn't know much in those days -- but did do a combination of high dose riba and double dosing. Was around two logs at week ONE. UND at week 6. I"m guessing I would have been UND sooner had I not had to go completlly off the riba between weeks 2 and 3. In other words, in my case I don't think the double dosing and high dose riba mattered since my week one response was from a single dose and 1200 mg riba. But of course I didn't find out my week 1 result until week 3. Certainly getting faster PCR results is a helpful adjunct to personalized treatment, not that anyone could have pulled me off those drugs anyway once I went into "warrior" mode. But on reflection, don't think I needed the xtras.

[alagirl]

2x the interferon.  Ouch.  My joints hurt just thinking about it.  

[alagirl]

but would pre-dose Procrit as well
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no doubt.  If I wasn't an acute and could have taken the time to ramp up I think pre-dosing the procrit even prior to beginning the riba that was being pre-dosed prior to the interferon would give me a leg up.  I was only able to pre-dose epogen to a much smaller degree because of the more limited amount available to me at the time.  If I'd had three or four weeks with the same procrit availability I have now prior to beginning the riba I think I would be having a far easier time of things and possibly would be ahead of the curve instead of dragging tail behind it like I am now.  I might've "pre-dosed" my bank account too if I'd had a little more time. ;)

[FlGuy]

Just to add, the pre-dosing of weight-based riba was immediately followed by doubling the peg (2 x 180) for 4 weeks as well. Then, the rest of tx was 'normal'

[jmjm530]

Apparently there was a pre-dosing trial -- or so someone here seemed to report over a year ago -- but I've never been able to find that trial. Anecdotally, FlGuy pre-dosed two weeks and RVRd at week TWO. Not bad.

I've thought for some time that pre-dosing riba is the way to go and am surprised no real data out there on it. If I was in a hypothetical treatment scenario, and had to fight th virus agressively with SOC drugs -- I would not only pre-dose the riba for 4-6 weeks, but would pre-dose Procrit as well, plus I would arrange for HPLC testing of serum riba levels and try to get my levels up to at least the levels the Swedish Pilot study found therapeutic. But I'd do it before I started the Peg, as opposed to at the same time as in the Swedish study. Certainly not suggesting this approach to anyone, but as long as we're talking theory.

-- Jim