I am a null responder with early cirrhosis- liver function so far is quite good. Have been waiting patiently for telaprevir approval and just received devastating news from my consultant that for people like me telaprevir is very disappointing- only 14% chance of SVR ( based on data released at EASL 2011).
This very depressing news was given alongside warnings about viral resistance and potential exclusion from other trials further down the line because of failure with a protease inhibitor (if I do fail).
My consultant was talking about quad therapy like the Roche trial now in phase 2 and believes quad therapy is the future treatment of choice for null responders. The Roche phase 3 quad therapy trial won't come around until the end of 2012. I can't wait that long, but nor do I want to be excluded from more promising treatments that are on the horizon.
I feel utterly stuck and damned either way- any advice or alternative ways of viewing this situation would be really welcome.
I now have to try to glean information from those who know and also keep watching how other people choose to deal with these difficult decisions and try to make some sort of informed choice. Can anyone lend a hand as I can't think straight now !
Don't give up, hang in there. I don't have much knowledge to share on Tela/Boce, but hopefully someone more knowledgeable will pop in and give you their perspective.
What I will say, though, is that my husband was diagnosed with 'borderline' compensated cirrhosis in 2007 (liver function NOT quite 'good'), but has stayed stable for 4 years, so with early cirrhosis and good liver function your prospects of getting to 2012 are excellent, imho. And remember, statistics are only that: my husband was given less than 20% chance of success with SOC, and he got to undetected; so even if it is 14% chance, you might be one of that 14 in 100. Just a couple of thoughts -- keep calm and keep thinking it through! Good luck with it all. ~eureka
How null is null ? ie what did your VL drop look like?
Your consultant's take sounds on target. Quad tx will definitely be the best option for nulls - the equivalent of what triple is for relapsers. End of 2012 for start of phase III quad trials sounds unduly pessimistic however. BMS appears to be moving forward more aggressively than Roche (who is raking in tons of cash on Pegasys sales and presumably in no hurry to see that dry up). Scouring all upcoming trials (BMS/Gilead/Pharmasset) is a good idea. If you can't wait further, supplementing with what's currently available (high dose RBV, Alinia/NTZ, IV-SIL, SAMe) might improve your ifn response and thus your odds with triple. Best wishes.
Hi Paul, I am in exactly your position. I am a previous null responder (1.9 log drop at 12 weeks) and I have had cirrhosis (well compensated) since my first biopsy in 1992. My NP is a previous Hepatitis C Clinical Trial Research Nurse with a large practice in NJ, and she thinks I ought to try the telaprevir. She does not believe it will necessarily keep me out of future trials and she said that resistance isn't much of a problem for genotype 1b's. Even if you are geno 1a, the resistance seems to go away after a while.. There is no way to know all of the specifics about a person in a trial and why they did or did not SVR. She recently attended a talk by Dr. Eugene Schiff, at UMiami, and he said he has had some good luck with his previous null responders with late stage disease. I think I am going to take her advice and try. Lets keep each other in the loop regarding anything we may find out.
Thanks. My viral load didn't go down 2log over a twelve week period, think it was only about just over 1log drop.
Hope I can get more responses so I can build some clarity as this is driving me a bit nuts, there doesn't seem to be any end to waiting.
As we all know the less diseased the liver is the greater the chance of SRV. Since you are "early cirrhosis" you may have time to wait for newer meds but it could be a gamble. Each individual is unique in how their liver disease progresses. I was stable for years and then had an operation that the anesthesia damaged my liver and caused me to decompensate.
"The diagnosis of early cirrhosis should not be considered a fatal diagnosis. Most patients will continue to do well for decades. There is no reason to refer a person with cirrhosis to a liver transplant center unless the cirrhosis is advanced (CPT class C) or complications from cirrhosis have developed."
27% or 17% is better then about 0% in the case of SOC. I will be try treatment (as a former null responder) as this may be my last chance before transplant. I figure I have nothing to lose and all to gain. We have to accept our health status and do what we can given the circumstances. Sure it is disappointing when we hear the 80% SVR rates but that unfortunately that is not us. We do what we can with what we have. You can choose to look at the glass half full or half empty. Both are true. But for me I have to be optimistic. What can I do throw my hands up in the air and say this isn't fair. It is not fair. What is happening everyday to our fellow suffers of liver disease isn't fair either.
In the big picture we have it easy. We have cirrhosis yes, but we are not experiencing life threatening complication or a regular basis like so many are as they wait for a donated liver to be available. If you want to feel better go to the nearest transplant clinic and visit and talk to a patient there. You will walk out thinking you have it made and will feel fortunate and lucky to be so healthy. We can still walk, talk, take care of yourselves, have a normal life and not be bed ridden as we suffer and fight for our lives every day.
No cirrhosis is no bed of roses... even without symptoms, we know are livers are scared progressing toward failure every day. It is all relative as Einstein said.
Hang in there. All hope is not lost. A Yogi Berra said "It ain't over 'til it's over". Take it one step at a time. Do what is right for you and your values. Enjoy everyday of life and realize how precious it is. None of us are gonna live for ever. "No one get out alive". One day it will all be over, so enjoy yourself now. If you want to do something do it now. Don't put it off. You don't want to have regrets. Do something foolish or crazy but with a sense of respect toward others. Who cares really? This is your one and only life. Make it the best you can while you can. Do what makes you happy. It doesn't matter what anyone else thinks about it. It is your life not theirs. As Hendrix said 'I'm the one that has to die when it's time for me to die, so let me live my life, the way I want to."
Okay...sorry I'm getting off my soap box now....whew...
Just a few suggestions from someone who isn't an expert on Tx:
-- PIs (protease inhibitors like Boceprevir and Telaprevir) are not the only game in town. There are all sorts of other drugs now in trials. One of the more promising (to my mind) is Globeimmune's GI-5005 immunogen, which has recently reported some trial success with null responders (see the news articles at Globeimmune-dot-com), and also particularly with people who have the IL28B T/T genotype.
-- Have you tried to find out why you are a null responder? Knowing the cause of a condition is the first step in dealing with it. Cause and effect is the basis of all knowledge, and knowledge is power.
-- Trying to get rid of the virus is only half the fight. The other half is keeping up your liver function. There are things you yourself can do for that. Some are: diet, exercise, and alternative meds (silibin, PPC, ALA, Vitamin E, SAMe, Lactoferrin, etc., and especially the immune system boosters). Believe it or not, some of them do work.
Maybe you know all this stuff. If so, I apologize for wasting your time. However, I'm a firm believer in self-help. It keeps you from slipping into a dependence syndrome. Taking action is one of the best medicines around.
Paul, Mike's post reminded me that my NP has put me on Milk Thistle (175mg) 3 X day, Apha Lipoic Acid, total of 600 mgs broken in to 3 doses a day, and Lecithin 3 X day. Also, I love Hector's attitude. I have had cirrhosis since my first biopsy in 1992. I am still well compensated and look how long it has been. You will be here to try many things if the PI's don't work.
Pure PPC (polyenyl-phosphatidylcholine) is better than lecithin, of which it is the active extract. Lecithin, which is basically cleaned-up soy oil, has some bad stuff in it. Sure, pure PPC costs more, but so what? Why take a lot of lecithin when it's been proven that the part of it that's active in protecting the liver is the PPC? Check out Phoschol and Hepatopro. I take the Phoschol, myself.
Ditto re milk thistle. The silibin phytosome (Siliphos, Ultra Thistle, etc.) works better and faster. A lot more of the active part of the thistle gets to work in you when it's in the phytosome form. This also has been proven in tests.
Re ALA, please allow me to suggest taking it between meals, if you don't already do that. ALA is not easily absorbed, and in fact most of it never gets to where it should (those places where it can reduce natural but oxidized glutathione). Taking it on a near-empty stomache helps for it to get used. There is even now an ALA time capsule, so that it hangs around inside you all day.
Vitamin E is another good antioxidant. Many normal people don't get enough, especially older people, and it helps to slow down the oxidation in the liver that causes fibrosis. It has synergy with Vitamin C, too.
There's a ton of info in earlier Medhelp threads on all this.
Sorry if I sound like a wiseguy. Just trying to help.
I forgot to mention that for inspiration and ideas on what you can do, check out the Medhelp threads from Gauf and HR from a couple of years ago. Gauf is one of my heros. With advanced-stage liver disease, he finally cleared the virus on his fourth (or was it fifth?) Tx, using a formula he himself put together, a combination of modified standard therapy plus a regime of alternative meds. This is a guy who knew he was going to win and did, by relying on himself and taking action.
I think those threads are still available in the Medhelp archives by doing a search. If not, there are people here who have saved them as files in their computers.
Not a wiseguy at all. I really appreciate the advice and will look for the forms of milk thistle you recommend. So the Phoscol is the extract of Lecithin that is better? Did I understand that correctly? I will ask my health food guy if he has it. I do take the ALA between meals.
Thanks for your posts guys advice and info taken on board and appreciated. The only supplement I'm not taking is the phoscol- still trying to find something I can afford in that area.
Hector- wise words thanks
the 14% Paul's consultant mentioned comes directly from the data submitted by Vertex as part of the FDA review. See the bottom of table 15 on page 67 of
Of 50 cirrhotic null responders in C216(REALIZE) 7 (14%) reached SVR combining the lead in and no lead-in arms (vertex concluded lead-in had no major impact on svr). By comparison among controls on soc, 1/10 reached SVR.
Stats are just stats, but for now that's what there is to go on. It seems a very tough call. For Susie whose 1.9 drop puts her very close to response trying to nudge a slightly stronger ifn effect seems very tempting. But a 1log drop by w12 may call for heavier caliber ammo. The maddening thing is that this quandary has been predictable for a long time and the FDA could be helping by providing early access to quad where need is apparent.
Though there's still no retx data on past triple failures, and likely won't be for at least a year, it seems a reasonable bet that failed triple won't preclude reuse of a PI in quad. However, exclusion from future trials is another issue. From posts here it sounds as if the guidelines there are pretty strict.
Hector - I wish you all the best this summer. Your attitude is terrific!
in the same way supplements like PPC and silibin may be effective in slowing fibrosis progression it may be helpful for those planning triple tx notwithstanding a lukewarm ifn response to try and boost it,
My personal experience with this has been positive (see the graph in the "limbo limbo" journal entry). Addition of alinia, SAMe, high dose rbv yielded a better ifn response in my current tx (lt 5iu at w8) than in my last attempt in '03. For all three agents there is credible peer-reviewed literature supporting enhanced ifn responsiveness. However given a sample of one it's obviously impossible to tell which factors were significant, if any, or whether this was simply due to chance. Supplementation of this sort was not an option before approval but might be helpful as a way to boost triple tx.
Also as Mike716 mentioned, trying to track the cause of non-response, with weight/IR being the clearest example of a factor under patient control, is worthwhile.
Some good replies. I particularly like willings last summary of a few replies.
First of all, there could be a large difference between cirrhotic null responders and a null responder with *the beginning* of cirrhosis.
Segundo..... there may be a difference in being able to treat with a PI in a trial and being denied a rescue drug versus treating with an approved PI and being able to use rescue drugs. Vertex ran very tight trials and in some cases they would do a riba dose reduction when anemia hit a certain point. In the first 6-12 weeks of TX this was really a critical time and..... people ultimately failed triple therapy. Who knows what the SVR rate would have been in such cases with rescue drug intervention? I don't, but it *could* make a difference.
Third..... I have a friend who just SVR'ed on the 3rd go around. Empirical evidence suggested that she would fail here third time.
THIS TIME.....she lost weight, exercised, did milk thistle, vit D and a few other adjuncts. Guess what? This time after failing a 65ish week and 48 week TX ...........she achieved a RVR and an ultimate SVR.
IF you do nothing to differentiate yourself from the average TX'er you'll tend to get average results. Try doing everything right; I'd bet you'll see better results too.
4th.... Unless your consultant is clairvoyant they really don't know if you are going to be accepted into a trial, if you can get into one of the really good ones and if you will end up in a rock star trial arm. you could, in some trials end up in one of the under-dosed, too short of TX, arms of a trial and end up with an ultimate fail. Trials after all are designed to differentiate outcomes. That means some will fail. Do you really need to wait a year or two for some game of chance? If so....start scouting; some trials are better than others. Some offer better odds. Clearly a 3a or 3b/ post approval trial may be one of the best options.
I am hopeful that some future trials will switch to triple therapy as the "control/ placebo arm" and we will see improved response rates in these trials.
Willy- The riba dose reductions during trials is an angle I'd not thought of. That would have to make a big impact on those with lots of liver damage. The damage alone keeps Joe in a state of low hgb before you throw riba at him. His first two TX were doomed to fail because of riba reductions. If Procrit isn't waiting in the wings ready to use, I wouldn't even want Joe to think about starting TX. As some of these things become clear, I'm so glad he didn't make it in to prove 3 although I was quite sad at the time. It likely would have been another discouragment.
Willing and Mike716 -Do you remember the explanation HR gave as to why plain lecithin would not be effective but PPC would? I know he went in to it in a lot of detail and put great emphasis on the fact that it needed to be Polyenelphosphatidylcholine and not just choline or lecithin. I remember a study he made reference to that had increased SVR's using the PPC form during TX. It is certainly an example of how important the fine details can get, especially to the marginal responders.
Hey thanks some great responses here. In comparison to my last failed attempt with SOC I feel in some ways better equipped now- over two stones lighter, careful diet and all mentioned supps apart from PPC.
I will digest the wisdom and make my case with specialist in two weeks time.
Ev...... several things worth mentioning; First, they didn't use much anemia helpers in the Vertex trial, but did in the Boceprevir trial, so some things can be compared and some things not.
Second, I believe the PI's in and of themselves may also create more anemia, even without the SOC. If Joe's issue was anemia it will probably continue to be so, except possibly worse. In such cases a sharp doctor or even a hemotologist may be another useful consult or back up if the issue were to pop up again. If one can weather thru the first 12 weeks without reduction the chances of success are far greater.
Third, since it appears that Joe is improving in some respects.... is it possible that waiting a little might even mean a better outcome?
If one looks at alcohol use...... just stopping right before TX does not really impact response rates dramatically. Somehow the body takes some time to recover before the absence of alcohol starts to impact on increasing the response rate. It could be that over time Joe may have a different response profile than his earlier one.
This is kind of muddy and there isn't a lot of data supporting this but it could be that some of these lifestyle and supplement changes are something that need to accumulate, and are not something that one can start the night before TX, just to reduce this concept to the absurd. If so, like my friend who succeeded on her third TX both Joe and 22hamilton may have a more successful run next time around.
Thanks for your input. The biggest strike against Joe trying for the fourth time is that he just isn't mentally up to facing the miserable SX again. I see his face when we discuss it and in my heart, I can see he's not ready.
Now , if he hears the unmistakable voice of God telling him to do it and it will work this time...(kind of like "Build it and they will come" :>) I'm sure he would go for it. Having not heard any voices lately, he seems not inclined to try it. Maybe later, but not yet. If he holds out, maybe he'll make it to the non-interferon TX. Maybe someone will figure out an antidote to why some people are so sick on TX while others aren't so bad.
I keep hearing mention of people's Dr.'s allowing them to take milk thistle on TX now and I have wondered if this will help some feel better. It seemed to have that effect in the HALT C trial. This is something I will be asking at Joe's next appt. I'm forming my list . :>)
I was surprised that after giving Joe 500 IU's for a year, his levels were still very low. That was a long time ago when HR had first talked to us about the importance of vitamin D on TX response. There has been so much more info available now. Joe takes 3000 - 4000 IUs daily and has for several years. I've heard of some Dr.'s ordering gigantic doses for a while until levels get up but I don't know if this is as effective or desirable as a slower build. There just isn't anyway to know where you are at without the test. Now Joe's Dr. orders it as a matter of course if there is any chance someone is going to be on TX.
I sure hope this will be the one that works for you.
I believe Phoschol and Hepatopro are the same thing, but I like Phoschol's online info more (see nutrasal-dot-com).
I did a lot of research on polyenyl-phosphatidylcholine (even more specifically DLPC [dilinoleoylphosphatidylcholine]) a couple of years ago, and there seem to be only two maufacturers/suppliers, one in Germany and one in the U.S. The U.S. one is Avanti Polar Lipids. However, all of Charles Lieber's original studies were done using the German product, which I was never able to find a retail source for in the U.S.
Of course neither of the manufacturers will sell it in bulk to us users, so we have to pay for the fractionated Phoschol, Hepatopro, etc. I get my Phoschol from Betterlife. They may not be the cheapest source, but their shipping contact is a cool guy named Kaz who will do you favors.
I've actually wondered at times if a lot of this stuff was just the usual supplement/nutrient hype, and if garden variety phosphatidyl choline (much, much cheaper: see NSI) or even lecithin weren't just as good as the souped-up above products. But I figure, why take the chance? And I know that soy oil has a lot of really bad stuff in it, like the wrong fatty acids. So at least with Phoschol and Hapatopro you're getting highly purified phosphatidyl choline.
If I were you and really couldn't afford Phoschol or Hapatopro, I'd go for NSI's plain-vanilla phosphatidyl choline. It's one seventh the price of Phoschol. Here's the link:
By the way, for anyone interested, I think Vitacost/NSI are the king of cheap generic but trustworthy neutraceuticals. I buy a lot of stuff from them.
The thread is still there (I just checked). It's a long thread with a lot of good stuff in it. I've got most of it saved as a text file on my hard drive to protect against virtuality disaster [grin].
Towards the beginning of the thread HR posted an extract from the1998 article on the successful PPC + Interferon multi-center trial results ("A biochemical response (> 50% ALT reduction) was seen in 71% of patients who were treated with PPC [+ interferon], but only in 56% of patients who received placebo"). That article is well worth a read, difficult as it may be. A very interesting trial from back in the days before Big Pharma cornered the market.
The study of what phospholipids do, and especially how they affect cell membranes (which has to do with PPC protection of hepatocytes) has grown into an entire new area of biochemistry and pharmacy. Lipids are being used to enhance drug delivery, an example being the silibin phytosome. And they may be a key to controlling the entry of virus into, for example, hepatocytes (as appears to be the case with PPC combating liver fibrosis).
PPC is not just another nutrient, as HR tried to make clear.
Sorry for hogging other peoples' threads, but I just wanted to say hello to Willy, Hector, Willing and other old Medhelp acquaintances. Maybe the nicest thing about dropping into the forum from time to time is meeting old friends. Kinda chokes me up, to be frank. I don't know where I'd be without you all, stuck as I am down here at the other end of the world.
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