Thank you for posting this. As a post-transplant who will probably be starting triple treatment in Jan. or so, I don't know if this information is encouraging or discouraging to me. There have been so few post-transplant patients that have tried it, that I'm sure my doctors don't know exactly what to expect. But the info is enlightening.

Yes Marilyn I thought of you right away when I came across this article. It does have good and bad news bit I felt more favourable!
Knowledge is power so I wanted to share with you.
Best of luck and hope your toe is healing up!

Scarry to be a pioneer but these results look encouraging.... not easy, but with great potential for a good outcome. I think all of us on triple are pioneers and we won't really know about the long term effects for some time to come.... fingers crossed leap of faith is required (:

This is why I backed out of the very same study... Quote;

"Many patients (49%) required blood transfusions during triple therapy. During the first 16 weeks of therapy, these patients used a median of 2.5 units. The majority of patients (86%) used growth factors, including granulocyte-colony stimulating factor in 44% and erythropoietin in 79%. Medication dose reductions were most frequent for ribavirin (in 78%). A total of 7% were hospitalized for anemia, Dr. Burton said.

Renal insufficiency, defined as an increase in creatinine of greater than 0.5 mg/dL from baseline, developed in 32%. Of two rejection episodes in the study, one involved a patient coming off a protease inhibitor."

I remember about a month ago, I posted a link that explained in much greater detail, the very same sides this article has and the percentages were about the same as well... When I find that link, I'll post it again and/or I'll just send it to you PM.

I'm very fortunate that I don't have cirrhosis yet and my stage 2 fibrosis hasn't progressed at all since the last time I treated...

Marilyn, If I were in your situation - I would definitely treat!!!

See if you could opt for a long lead in time as opposed to a short lead in because it gives your Dr. greater flexibility while treating you...

F0r instance, let's say you've been on the Peg & Riba for quite some time prior to starting the protease inhibitor and I don't know which one your Dr. is going to prescribe you...

I believe the Dr. will see how much improvement with the first 2 of the triple has done so far... At this point they can gauge whether or not if it's even necessary to put you on the protease inhibitor or not!!! If they see a substantial improvement that buys you some time, then I would suggest that they keep you on the psgIfn/Riba combo with out adding the protease inhibitor!

This way, you can last as long as it will be necessary in order to get put on the newer polymerase inhibitors instead!!!

You will also avoid having to take the protease inhibitor with all of the potential dangerous sides that for me are not worth trying with the track record of them so far...

Now remember that You're not in a trial study and also what I told you is a suggestion and nothing more!

This suggestion also gives you something to introduce into your meeting with your Dr.'s coming up soon enough.

So, I will pray for you that you get the same results or better that I did when I was on treatment last and that's also something to consider as well. Besides, you owe me a cup of joe to have with your friend Ron and you!!! All the best to you!!!

Respectfully,
Henry

Hank, that is a really interesting thought, i.e., extending the use of riba and peg, more of a lead in time than "usual", to assess how the two alone are working. Now my question: why? Am I to understand that the PI's are causing problems in addition to those already known to be possible with just the old SOC? Yeah, I guess so. By "problems" I'm asking about other than the "gastro" issues with Incivek, and, if I'm not mistaken, more of a propensity toward anemia (in addition to what can happen with riba) with Vic? This is why the new polymerase inhibitors are so needed. 49% needing blood transfusions on triple? That is a huge number! I wonder if they were on Victrelis?

If I'm right, this is what my doctor is talking about doing in my case (IF I treat) - longer lead in time with Peg and Riba - to gauge whether I'm responding well to them before adding the PI. We didn't discuss it much since I'm not ready to make a decision about treating. However, he certainly did say that I need to treat.

Marilyn and I are the same stage and about the same age and tx naive. Of course, Marilyn is post-transplant, which I'm not, and we each have other differing circumstances. I just want to again say how brave and incredible and beautiful our Marilyn is.

Well cat, You just answered your own question...

" Now my question: why? Am I to understand that the PI's are causing problems in addition to those already known to be possible with just the old SOC?"

Correct!!! You see, Both Marilyn and myself are post transplant and because of this, we have to take immuno-suppressant drugs (Cyclosporine for Marilyn & Tacrolimus for me) which complicates things with respect to treating with Telaprevir...

These protease inhibitors (Not much data on Boceprevir since only 10% were on it) change the whole ball game when used with post transplant patients because they are known to inhibit the metabolism of calcineurin inhibitors, which was reflected in the study by the need to reduce the median daily doses of cyclosporine (from 200 mg to 50 mg) and tacrolimus (from 1.0 mg to 0.06 mg) after protease inhibitor therapy began...

When post transplant patients have such a reduction, the possibility of organ rejection increases substantially and I don't speak for Marilyn but, I personally do not want to take that chance!

When i read their results and then compared them to another article that explained what would happen if I were to take the protease inhibitors mentioned while I was on Tacrolimus (ProGraf, FK 506) this paper only validated what I read in the previous one and was very influential in my decision not to participate in this very same study...

Now Marilyn's immuno-suppressant named Cyclosporine is different than what I take, and the effect of reduction in potency from the Telaprevir is 75% compared to 40% on Tacrolimus!

This is a substantial difference and it's even more dangerous for Marilyn than for me with respect to the increased possibility of rejection because of the insufficient blood levels of immuno-suppressants to basically fool one's own immune system into accepting the transplanted organ...

The other issues I have are the increased possibility of having to go through more blood transfusions because our immune system is in chaos from the reduction in potency of our immuno-suppressant drugs!!!

Now, the Dr.'s can make up for the potency loss of the anti-rejection drugs but, I'm very leary about letting someone mess with my anti-rejection/immuno-suppressant drugs by "guesstimating" the correct dosages for me to avoid organ rejection... Why???

Because for 15+ years I have managed very well so far in maintaining the healthy relationship my body has with an organ such as the transplanted liver from another person who died and yet, part of him still lives on!

Finally, there's the renal (Kidney) issues which I already have had my share of throughout my transplanted life and I certainly don't need anymore of it and neither does Marilyn... For instance;

"Renal insufficiency, defined as an increase in creatinine of greater than 0.5 mg/dL from baseline, developed in 32%."

To me, that's just plain dangerously unacceptable and I can't speak for Marilyn but, I believe that it would be harmful for here as well!

"Of two rejection episodes in the study, one involved a patient coming off a protease inhibitor... "

Only 2 in the study but, they don't mention how many would have rejection episodes after the study and that's what really bugs me!

So I hope I explained it enough in a manner which would be helpful in understanding what the side effects mentioned in the article could do to both myself and Maryilyn...

It's not the SOC that I'm concerned with because it has kept my transplanted liver from being devoured by HCV over the many years since my transplant and has even granted me SVR for over 2 years more than once...

It's the Protease inhibitors like Telaprevir that have me worried, and repulsed to the notion that after all these years, I would risk my transplanted liver and my life for that matter on a drug that has already been proven to make SOC seem placebo like in comparison and is proven to be dangerous to my health.

Respectfully,
Henry

Correction; When I wrote "effect of reduction in potency" I really meant to say this instead;

"to reduce the median daily doses of cyclosporine (from 200 mg to 50 mg) and tacrolimus (from 1.0 mg to 0.06 mg) after protease inhibitor therapy began.

In other words, lower the dosage of what a patient is currently on which is very dangerous to say the least!!!

Giving too much of a dosage isn't good either but, it's definitely not any where near as dangerous with respect to increasing the potential of organ rejection by reducing the patient's normal dosage!

This last paragraph summarizes what they have learned so far and what they need to improve on;

Dr. Burton suggested that future studies should focus on identifying predictors for nonresponse to avoid unnecessary treatment and associated toxicities such as complications of anemia and adverse events related to significant protease inhibitorcalcineurin inhibitor interactions, such as worsening renal function and graft rejection when transitioning off a protease inhibitor.

This is what will mess someone like Myself & Marilyn, and why I'm not going to treat w/Telaprevir;

"such as worsening renal function and graft rejection when transitioning off a protease inhibitor."

So worsening Kidney function during treatment while on Telprevir and once I'm off the Protease inhibitor, the chances of organ rejection become more prevalent!

Respectfully,
Hank

I'm going to have to read this a few times to fully wrap my head around it, but oh yes, I do get the basic concept. Thank you for the detailed posts - for the knowledge you have and you've shared. For sure, you know your stuff, and it pays off when things like this come along, i.e., the idea of "treating" the virus in a transplanted liver with the triple tx.

My heart absolutely breaks for Marilyn - that she is now in early cirrhosis - after all she's been through, she has this happen. It is so so unfair.

Prayers for Marilyn - prayers for you too, Hank. Prayers for all of us, in fact. I remember how surprised I was to learn, from this forum I'm sure, that a transplanted liver most likely will be reinfected by the virus - the virus lurks in cells and attacks the new host. It is truly "the beast."

Your welcome Cat but, before you stroke my ego any further, and I know you don't mean to intentionally, I'm no more knowledgeable than you or anyone else in here that's very determined to learn as much as they can because after all, I've got more to learn tomorrow!

So Cat, I admire you too for your absolute honesty and humility when you talk about your journey and how you desire to make things right for yourself!

You're a very brave and courageous woman who has learned to face your fears by turning them into faith from what I can read so far... Oh and I'm not trying to stroke your ego either. :>)

You just keep at it Cat... You'll know what you have to do.

Respectfully,
Henry

Thanks, Hank. Yes, you are reading into it right - that's what I'm doing, or should I say, what I'm working on: "learned to face your fears by turning them into faith from what I can read so far... "

This is something that I didn't plan to do - but it subtly evolved over the past few months or so from a place in my heart and soul that this was the way for me to be able to move forward, to not stress and worry so much, to ask for help from a Higher Power and to have faith in that Power. Marilyn gives me a lot of this "insight" just by being who she is and how she is. She is the Wise Woman Warrior here.

I am trying to deal with all this - just as everyone here is. I feel that I should make a decision by the first of the year re. whether or not to do the triple tx. If I don't - then what? The virus continues to replicate. And it's gone far enough - I'm still early cirrhosis, but it won't stay that way, not when I realize that the virus became so aggressive the last few years - based on comparisons of ultra sounds, CT scans, labs, and then that botched biopsy, which nonetheless, was "good" enough for three different doctors to assess early cirrhosis.

Bless you.

Henry, my creatinine was already 1.4 on Jan. 7, two weeks after they increased my fluid pills dosages. I'll have labs again tomorrow morning (Mon.), and I'm afraid to see the results. So yes, I'm leary of kidney problems with triple treatments.
My transplant team will be discussing my case on Wed. to "form a plan". I'm going to email a note to my coordinator tomorrow morning to take with her to the meeting (since I wasn't invited to go), expressing my concerns and will also insist they get my lab report from tomorrow in time to include it in the meeting.