post liver transplant, hep c attacking new liver

[mary921]

I am 47, I had a liver transplant 10/99 I have hep c, hep c is attacking new liver. I was on Pegasys and ribovarin last year which did not work,
any new meds or treaments out there? what about filtering the blood like in dialysis.

[cajunlady]

Mary I am sooo sorry that this is happening to you.  I do not know any answers, but Mike had a transplant and I tried to flag him with this thread.  He will probably have answers.

Cajun

[NYCMark]

Hi Mary. How did your transplant go? I guess (except for the current HepC problem) all went well.

My understanding is that hepatitis C recurs in just about 100% of patients who were RNA positive for it prior to transplant. So while this is of slight comfort to you, it is certainly not unexpected. Perhaps your transplant coordinator or physician knows of studies available to post transplant patients?

Best luck to you with this problem.

Mark

[cruelworld]

ive heard they are working on a dialysis type thing for liver failure  but its many many years away, if ever. the liver does too many complicated jobs.
i am not an expert but i think your only choices are to try different versions of interferon, instead of pegasys, try infergen or pegintron, this is a standard techqnique when faced with bad or no response. also the approach of larger doses.
if all this fails, hopefully youve bought yourself enough time to wait for new medicine. a member here mike simon had a transplant and  had to treat three different times before he finally defeated it. i expect he will give you advice when he sees this message. have a good day!

[Jeff88]

Mary, Mike Simon is the most knowledgeable here about post transplant treatments and he will probably respond soon.

I had a transplant in 2002 and am on tx now. Went one time through a rejection too. The key questions are:

1) How much anti-rejection medications are you taking? I assume you are on prograf? Do you take other AR meds as well? Hopefully your team keeps you on the right dose so you are not oversuppressed.

2) Maintenance treatment (half a dose IFN + about 400mg Riba) is also an option that some have tried. It supposed to keep the VL low and limit the damage, so you can buy time until new drugs will be available. There is a large study now, called STOPC, which by the end of the year may give us more clear answers.

3) The new drugs are coming, but it may take time. So far the only option is various types of interferons and finding the right balance between them and AR meds. I hope that you under care of a good experienced hepatologist, if not, actively seek second opinion. There are many posts here with names of leading Drs in the nation, both on east and west coasts.

Please keep fighting. I know how exhausting it is, but things should and would stabilize.

Best of luck to you.

[mikesimon]

Hi Mary. I have a few of questions.
What is your Genotype?
When you treated did you respond at all? By that I mean did your viral load decrease and/or did your enzymes come down if they were elevated when you started treatment?
What were your doses of Pegasys and Ribavirin?

In answer to your questions:
Yes, there are new drugs that look promising. The ones that look the best are protease inhibitors but they are still in trials and not yet available and I have not seen any trials accepting transplant recipients but someone may know differently.
There is no blood filtering treatments that I am aware of and I believe I would know if there were any treatments like that available.

As cruelworld stated I treated 3 times before I became a sustained viral responder and the third time was for a 73 week duration at full doses of Pegasys and ribavirin. My experience is that transplant centers have been reluctant to treat their patients with optimal dosages of interferon and/or ribavirin. I believe there was a lot of concern about rejection episodes triggered by interferon but my understanding is that is not a common result. Many transplant recipients stop treatment because of side effects which seem to be more severe in the transplant population which I believe is due to bone marrow suppression and the anemia that results from adequate doses of ribavirin. I would not be surprised if you were treated with low doses of either or both drugs but perhaps you weren't. I will watch to see if you respond and if you do I will try and be of more help.

Mike

[Jeff88]

Mike,

I hope I am not stealing the thread as this question may be of interest to Mary as well. How were your AR meds managed during your 73 wks Tx?
Have you been on the same dosage all 73 wks? How much prograf? Did you take Rapamune as well?

I am now (21 wk) on 1 mg prograf; a week ago my Doc added 1 mg of Rapamune.
The riba is only 1000. No rescue meds so far, but CBC are getting close to where I may need them (e.g. ANC ~ 1000, WBC ~2.1).  From all that I hear I would like to up my riba to 1200, but my Doc is reluctant.

Thanks, Jeff.

[GoofyDad]

CPMC trial (ESLD only)


http://www.cpmc.org/advanced/liver/news/newsletter/livrev-winter05.pdf

[kcmike]

jeff & mike  
good questions and answers!  I to am PT (Jan 05). 1st tx w/Peg-Intron and Rebetol, GT 1b.  AR drugs are 4mg Prograf and 500mg Cellcept.  I'm in week 34 of 48, I cleared @ 12 weeks.  Still clear @ 27 w/ a Heptimax.  sx are manageable, still working full time.  Anemic of course, started Procrit @ wk 14.  

mary
I am participating in a Schering-Plough study.  If you want to learn more about it, go to clinicaltrials.gov, search industry and then Schering-Plough.  The study is called PO4590, #22 on the list.  It also shows research centers you might want to contact or have your doctor do it for you.  

i am interested in following your cases.  please post your news.

kcmike

[Jeff88]

So good to hear about your good response to Tx. 12 wk UND, it is very-very encouraging! From discussions that I hear here and general data that as PT we have a lower SVR chance, don't you think that if you can tolerate sx, you should go for 72 wks? Also did you noticed a change in your response to tx before and after TP?

Before TP, I tried twice and both times my enzymes went up to 500-800s by 12 wks. I needed to stop.

Keep up the good fight, man! I am so glad for you and inspired too. Jeff.

[kcmike]

I never had time to do SOC Pre-TP.  I went from stage 3 to ESLD in 6 months.  However, fyi my baseline ALT and AST were in the 50's and now in the teens.  Saw hepatologist today and discussed 72 wks, but no need for decision today.  Going to see what 36 wk PCR tells.  

Pre-TP my enzymes went over 500 and the last 6 months were nearly as bad as tx.  If I relapse, most of us do, my doc is already asking Schering-Plough for help with protease path.  

My problem is my Hgb.  I'm at 87% of my regular 800mg  weight-based dose of riba due to Hgb in the 8's.  No resue drugs for you at 21 wks, that's greeaat!
Keep posting, I've been watching couchpotato, buckaroo, BThompson, mikesimon and you.

mike

[BThompson4]

I am in week 50, cleared between weeks 20 and 22, and am going 72 weeks.

Geno 1a, pre-tx viral load greater than 3.5 million iu/ML; take 150 mcg peg intron weekly and 1200 mg riba daily (5'11", 200 lbs.); 50 cc's Lantus daily; transplanted 1/2001; F2 fibrosis in June 2005, down to no significant fibrosis and no sign of rejection in biopsy done in week 36 of treatment (my first and hopefully only treatment; did not treat or even have biopsy prior to transplant, liver was already too damaged prior to transplant from life threatening multi organ failure episode); took 100 mg of cyclosporine a day pre treatment and now take 200 mg cyclosplorine a day with never any signs of rejection and great creatinine scores (almost always 1.1).  Getting lots of pcr's for some reason; UND at less than 25 iu/Ml about twelve times since clearing in week 22.  AST on last five tests have been between 48 and 61; ALT between 76 and 91; both were about 20% higher prior to tx.

The sides have not been horrible (no rescue drugs needed; hgb not terribly low at average of about 11.2, but low enough for me to feel like I'm getting enough riba for a 72 week treatment to be successful).

UND at week 12 sounds awesome Jeff!  I guess it is tougher for post transplant patients to get svr.  Docs are getting better all the time at managing us though.  I am so grateful for the efforts of everybody that treated before me and their adding to knowledge of how to attack this disease.  Here's to praying that we never lose hope in this struggle.

[BThompson4]

How are your creatinine levels?  Some studies show that having poor functioning kidneys makes you more susceptible to anemia if given ribavirin, so that it might be easy for post-transplant patients with kidney damage to get too much riba, even at doses that are appropriate to their weight.

[mikesimon]

Jeff, I was taking 2 mg. Prograf and  250 mg. Cellcept. That was my AR regime throughout the 73 weeks. During that treatment I became undetectable at week 12 and possibly by week 11. At week 10 my VL was 13 IU/ml or very close to that number and I didn't test at week 11 so I may have been undetectable then. At the time I weighed 142 and was taking 1000 mg. ribavirin and I attribute my response to the ribavirin dose which had been lower during my previous treatments - 600 the first and 800 the second and I weighed significantly more the first time - 178 lbs and about the same when I started the second round. The third was only 6 or 7 weeks after I finished 53 weeks of TX and that is why I was so light.
It is the plasma concentration of ribavirin that indicates whether the dosage is correct. Without knowing your weight I would suspect that your dose may be low only because your hemoglobin hasn't tanked and I would have expected that it would with optimal dosing.
KcMike, that is very good news that you cleared at week 12. I am reluctant to say anything that could cause you anxiety but I feel that I should mention that Cellcept in HCV patients is somewhat controversial. Back a few years it was thought to be a good agent for HCV liver transplant patients but I believe that newer studies cast some doubt of its advisability in this population. I should have research on Cellcept somewhere and if you would like I can probably find it. Maybe you've seen this information and have discussed it with you doctor and, if so, forget what I said. I don't think it will adversely affect your treatment - it obviously didn't affect mine but I was on a lower dose. I just cannot recall the issues raised with it but when I read it I didn't want to be taking it. BT is correct about renal function and its affect on ribavirin dose. Impaired renal function might warrant a lower dose. As I said it is plasma concentration of ribavirin which indicates proper and optimal dosage. My plasma concentration was never measured while I treated and I don't know how many center have this test available now.
BT, I am not sure that it is intrinsically more difficult for transplant recipients to reach SVR if treated with optimal doses for optimal duration. Many patients don't clear because they stop treatment due to sides and historically a lot of them have been under dosed. Back in 2000 the consensus was that HCV transplants did as well as transplants with other underlying diseases. It wasn't until a couple of years later that the truth began to surface - they didn't. I really wonder sometimes whether transplant centers focussed on 5 year survival and ignored or didn't worry about the longer road. When you see that 20% of HCV transplants are cirrhotic in 5 years if they don't treat it is clear that eradicating HCV wasn't the focus at many centers. I know that you're well into your treatment but I feel that I should tell you that Peg-Intron was tremendously harder for me to tolerate than Pegasys. I cleared late with Peg-Intron and knew I should have treated longer but I couldn't tolerate the side effects and stopped at 53 weeks. I started back within 8 weeks with Pegasys and a higher ribavirin dose and I cannot tell you how much easier the treatment was. I treated for 73 weeks and I could have continued treatment even longer with those drugs but I could never have done that with Peg-Intron. I tell you this just in case treatment becomes intolerable for you. If that happened I think a switch in interferon would be safer than a discontinuation of interferon.
I wish I had your creatinine level - mine is 1.3/1.4. My surgeon told me however that blood creatinine in people over 50 and particularly transplant recipients is not an extremely reliable marker. He had me do a 24 hour urine test and said my renal function was as good as it could be. I don't mean to suggest that a low blood creatinine level doesn't indicate good renal function - just that a mildly elevated blood creatinine level may not reflect accurately renal function - it might be better than the blood creatinine indicates.
Mike

[mikesimon]

I mentioned that Cellcept was controversial but I have been unable to locate anything specific which supports that claim. I feel pretty certain that I did read information which inclined me away from that drug but I searched pretty diligently and came up with nothing. So please ignore that comment of mine because it appears that it is unsupported.
This is all I came up with:

1) American Journal of Transplantation 2006; 6: 449–458
"Cyclosporine appears to have viral suppressive effects
in vitro (22), but in liver transplant recipients with HCV,
no significant difference in HCV RNA levels was evident
in cyclosporine-treated versus tacrolimus-treated patients
(23). Additionally, in prospective studies comparing the two
different calcineurin inhibitors, there is not significant difference
in HCV disease severity or risk of cirrhosis between
groups (23–25). There has been ongoing interest in the
effect on MMF on HCV recurrence and severity due to its
structural homology to ribavirin (RBV). No consistent effect
(positive or negative) on HCV histology and risk of cirrhosis
has been established (26,27)."

2) http://www.medscape.com/viewarticle/554635_3
Therapeutic Management of Recurrent Hepatitis C After Liver Transplantation
Posted 04/17/2007
"The helpful effect of mycophenolate mofetil (MMF) on HCV recurrence has not been confirmed.[97-99] Recently, Wiesner et al.[100] evaluated the impact of MMF on long-term outcomes by analyzing retrospectively 3463 patients transplanted for HCV. Although MMF combination with tacrolimus and steroids was associated with improved long-term patient and graft survival and lower rates of acute rejection, MMF did not show convincing histological benefits on HCV recurrence."

3) http://www.hcvadvocate.org/hepatitis/factsheets_pdf/transplant.pdf
HCV Disease Progression: Liver Transplantation
"Data on the risks and benefits of other types of immunosuppressive therapy, including mycophenolate mofetil and azathioprine, has also been inconsistent"

Mike

[BThompson4]

I know what you mean about some center's empahasis on five-year survival.  My viral load at 1.5 years post transplant was on 60,000 iu/ML.  I begged to treat then and every appointment thereafter.  By the time they would let me treat, I was over 3.5 million.

My thoughts that it is harder for post-transplant to clear is mostly governed by the fact that 30% of post transplant hep c patients are already pretty sick most of their time after transplant, based mainly on the fact that about that many die or lose their graft within five years.  Lot of them probably don't feel like taking on treatment after grueling process of getting a liver.

Like you, I have noticed some pretty good results in European studies and here for post transplant treaters.  SOC for them and everybody else, as bad as it is, is slowly being tweaked and becoming more effective.  So maybe my not treating when my viral load was only 60k (in 2002) was a good thing.  

Always appreciate the great info in your posts.  You have massive amounts of practical experience with his disease and have learned a lot too I think from your associations at your world class transplant center.  We have all benefited from your posts.

[kcmike]

BThompson-no rescue drugs for you and in wk 50, that's incredible!  thanks for your bio and the creatinine flag.  my creatinine in the last 6 wks has been steady @ 1.1 and that was my baseline.  

mikesimon-you are the guru of our subset.  thanks for yours thoughts and the links re:Cellcept.  Yesterday my hepatologist lowered my dose to 500mg from 1000mg.  Also, thanks for the links I will take a look at these and discuss with my study coordinator.  I share with him and he discusses with the team here at the Research Ctr.  

All:  http://www3.interscience.wiley.com/search/allsearch?mode=viewselected&product=journal&ID=112594473&view_selected.x=71&view_selected.y=8
Efficacy, predictors of response, and potential risks associated with antiviral therapy in liver transplant recipients with recurrent hepatitis C

[Jeff88]

Mike, thank you for sharing your treatment history. It is helpful in so many ways.
For instance, in my center they don't like cellcept. I was taking it for several months after TP in addition to prograf +rapamune. They like rapamune, the assumption is that it somehow prevents liver cancer. But it affects the lipids, a year ago it caused my triglycerides to shoot up to 800-1200, they took me off, but now I am back on it. With Riba I probably need to up it to 1200 (my weight is 170), don't know if it will be useful at this stage, 21 wks into tx. Many on the forum think that it should be "shock and awe" from the very start.

BT, I read your previous posts and know that you went through very rough times before TP. Glad you are doing fine now. We all have our histories which can be put into books and movies. Unfortunately, not enough energy to compete with Hollywood moguls. When I had to fight with insurance or get an answer from nurses, labs who are not helpful, not responsive, I often say that to have the luxury of this disease you have to be a very healthy person! HepC is not for sick people like we :)

Thank you all guys, let's keep in touch and hopefully the road shared will be easier.
Mary didn't respond... hopefully she keeps fighting and will be OK. We all know how it goes.
Have a great weekend.

One more thing, on the last visit with my Dr, he mentioned that he talked with Dr. Levy (not sure sp) from Toronto (?). I believe his group is well known. He is conducting a study of PT people on SOC treatment. The conclusion was that 72 wks (not surprisingly) gives much better results. But my Doc emphasized that his patients take cellcept instead of prograf.

[mikesimon]

My surgeon started me on Rapamune a few months ago along with my Prograf. I believe that recent rat or mouse studies studies have shown that sirolimus demonstrates an anti-fibrotic effect and may reverse fibrosis. Although my liver is stage 1 per biopsy 1 year ago I think the anti-fibrotic proerties was the reason he started me on it. Since he's a transplant surgeon our meetings are occasionally terminated quickly because a liver gets located and he's off to surgery. That's why I am not certain that the anti-fibrotic aspect of the drug is the reason I am on it - just when we were getting to that issue he got called and I didn't think it was a good idea to delay him any.. I took sirolimus early after transplant before it was available in tablet form. It was in a aluminum foil package and it was an oily substance that I mixed with water, I believe. It wasn't pleasant to take and I really don't recall why it was discontinued. I trust my guy so I basically do what he advises and get his reasoning later.
Rapamune does affect lipid profile and cholesterol so you have to keep an idea on that. My cholesterol was never higher than 105 and my LDL and HDL were beautiful but after 1 month on Rapamune my total cholesterol is 160. I am still fine but my number have definitely increased.
Mike

[Jeff88]

You are right, my doc actually was talking about anti-fibrotic effects, cancer was mentioned somewhat vaguely. He is not concerned with high triglycerides and said they can be treated by rescue meds. I was taking rapamune for 3-4 years with no significant change in lipids, but last year they suddenly started increasing. If your body will respond similarly, you can expect to see only moderate increase in cholesterol, but eventually triglycerides may start go up. I also believe it caused an annoying skin rash. I am taking clarinex and use steroid cream which is needed for Riba rash anyway. Lately, the rash was tolerable. Jeff

[mikesimon]

Thanks for the information and I assure you I will keep a close eye on my triglycerides and if I get a rash I will have a clue as to the cause. Take care and stay well, Mike

[mary921]

Thanks everyone for your comments, I always thought I could have a another transplant if needed, my doctor from Shands tells me they are no longer offering transplants to post transplant patients.  Apparently the hep c comes back worse, and they had 5 people die from it.  Was on Prograff until 3 weeks ago, I was then put on Celcept, because prograff levels were too low, and liver functions test increased.  Not sure what genotype I am , but I will find out today.  thanks

[mary921]

I will find out today what genotype I am.
last year in January I started the pegasys program with ribovarin.
I was doing the full dose in the shot and maxium dose of the pills.
It started out great, levels went from 7 million to 3500 by June, then they started creaping up again, and by December they were over 7 million again.

My doctor tells me I can't have another liver transplant.
Liver biopsy in January this year showed, active hep c, begininng stages of cirrhosis, and something else I can't remember.  

I had a ERCP in which they put 2 stents in the bile duct for 3 months then removed them.
I can tell when my hep c is active, I itch all over and I stay tired.
this is all very depressing.  I did so good for so long.

thanks for listening
Mary Ann