No UND

[zarmar]

We have our good days and bad as we go through Tx.  The past few have been on the bad side for me.  I was not UND at wk. 4 on Sov/Oly, nor at wk. 8.  In fact, my ALT and AST went up.  My hepatolgist gave me fretful input last week including a reminder that since I have blood cancer, I would not be put on a transplant list.  I am a 1a, ESLD - excuse me while I choke on that for a minute, no previous Tx history, Non Hodgkin Lymphoma (NHL) diagnosed last year, in partial remission so more immunotherapy likely soon, and platelets, WBC, PTT and INR, etc., low or slow and so I am a risk for Riba.

I am not sure about the SVR response I could hope for from next gen HCV Tx, and if I would be approved for insurance coverage given current poor Tx result to date.  There is a promising new NHL drug for relapsers due shortly, as well,  but it is liver toxic.  I worry that I have few options.  The lymphoma is a huge ongoing wrinkle.

[zarmar]

Thank you Hector.  I will pull the COSMOS data in discussing my status as a "gentle" nudge in an email I am preparing for the local Hepatologist.  My husband is less patient with sloppy input with such a serious disease, but I am still in Tx here.  I think it prudent to maintain working terms until that would change.  I will confirm about the Q80K mutation.  I recall that I was tested 7-8 years ago and have genetic hemachromatosis, homozygous for the H63D mutation and am heterozygous for alpha-1 anitrypsin deficiency.  Don't know full significance with cirrhosis, but iron overload has been checked in past.  I have so much blood drawn every week now, it may indirectly help keep iron in check.  I need to learn more about implications now that disease has progressed.  Knowledge is power.  

Best to you always - z

[zarmar]

It is amazing that one number - 0 - and three letters - UND - can so change the landscape of one's spirit.  I know I have more work to do, but encouragement that I get here is invaluable.  Thank you, Nan.  P.S. now switching back to address blood cancer matters.  This a bit of a dilution of UND joy, but I try hard to keep the focus on each step forward wherever it applies.

[nan535]

Happy to hear you are UND.  Now onward to SVR...
Wishing you the best while getting there.


Nan

[HectorSF]

Not being undetectable by week 4 is common, very common with your treatment. This happened to almost 50% of patients during the COSMOS trials!

And your doctor doesn't know this very basic fact about this treatment and is ready to stop treatment at week 8? I would seriously seek a second opinion should anything else happen during your treatment as your doctor apparently is not very familiar with the trial data and what is to be expected during treatment.

From the COSMOS trial data published over a year ago. that many people become undetectable after week 4 and achieve SVR is nothing new.
http://www.hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4024-croi-2013-simeprevir-sofosbuvir-demonstrates-good-early-cure-rate-with-or-without-ribavirin

"• 85% of participants in the ribavirin-containing 12-week arm and 57% in the ribavirin-sparing 12-week arm achieved rapid virological response (RVR) at week 4."

Also...
"No viral breakthroughs occurred during treatment."
"All participants (100%) in both 12-week arms had undetectable HCV RNA at the end of treatment"

Secondly when a person becomes undetectable has no effect on treatment success (SVR). Hopefully you doctor knows this?

" Rapid virologic response (RVR, defined as undetectable HCV RNA at Week 4 of treatment) was not found to be predictive of achieving SVR. In patients receiving simeprevir and sofosbuvir alone for 12 weeks, 93 percent achieved SVR, while 57 percent achieved RVR."

If you have any concerns about your treatment please talk to your hepatologist at Mount Sinai who is knowledgeable about this treatment and the trial data. She/he will confirm what I am telling you.

Just because you have had a rough start (due to someone lacking of understanding of this treatment) you have as much chance of SVR as anyone else on this trial as being undetectable before or after week 4 makes ZERO difference!

Treatment success is primarily based on your "host factors" when starting treatment. Not what happens during treatment. Those factor are whether you are genotype 1a or 1b if 1a whether you have the Q80K mutation. Those in addition to your compensated Class A cirrhosis are the most important factors determining your chance of SVR.

So remember you will stay undetectable as long as you remain on treatment. If your doctor does a viral load test during treatment and it says "detectable" it will be a lab error, so don't EVER stop treating. We have seen some lab errors here at our treatment center as well.

If there is any question talk to the Mount Sinai doctor who is familiar with Sovaldi treatment and he will tell your doctor this if he doesn't already know this.

Good luck with your treatment!
I am very sorry that your doctor really let you down.

Hector

[Livelife777]

Just popped in and read your follow-up.    May I be the 1st to say Congragulations!   Those happened to be the sweetest words I've ever
heard, when my journey began.   You go girl!
Just a bit of hope and alot of faith truly assists your inner gauge.
So very happy for you!
...Kim

[zarmar]

Great advice, the less than robust state of my "gut" notwithstanding.

Our inner gauge is our best referee.  

[zarmar]

This sounds great to me.

I will take it up with my doctor.  I appreciate the suggestion.  

[zarmar]

We can feel very alone since family and friends, while loving as they are, do not have this disease.  It is such a value to have this community to reach out to.  I don't feel alone in this company.

[zarmar]

Oh Hector - What a fantastic and wondrous difference good wishes and a fortress-like circle of support can make!  When I saw my hepatologist last week, he based his dire prediction on my status to date on not being UND wk 4 and wk 8 uptick in LFT solely - I didn't know that he hadn't yet reviewed the PCR for wk 8.  Praises be - PCR was posted to me today, and I am UND -- what a truly beautiful number 0 is.  I am thrilled.  I had been knocked to the ground last week.  If I didn't already have my last 4 wk course of meds, my doctor said he might have taken me off the rest of Tx.  I know this is a very costly Tx.  I could accept that if it isn't effective for my purposes, and with better treatments soon to be approved, my doctor might have started stepping me back from continuing.  However, he couldn't yet have known if it was effective for me.  As far as I can tell, he based his negative assessment on only partial information.  This resulted in an entirely unnecessary anxiety attack. I am so fortunate to have a consult hepatologist at Mount Sinai who was a clinician for Gilead trials of Sov.  I saw her for Tx input and review of my health profile end of last year before Sov was being prescribed.  She has been accessible to me without fail throughout Tx that I am receiving here in PA even though she is isn't my Tx physician. This may change for next Tx course should one be needed.

Re ESLD: you got me looking at it closely today.  From my April Trans Jugular Biopsy, my FIBROSIS STAGE = 4-5/6, and using last week's lab results, Child-Pugh is 6 - Stage A - thankfully, beyond any words that can do it justice, I am NOT ESLD.  A literacy issue from oncology support staff who aren't versed in HCV  My Cup Runneth Over.  While I'm not well, I also am far from dead.  There is a lot I can still do to achieve my health goals.

[nursehepc]

sorry...premature post...

challenges that....could relate their experiences to yours and provide you truly great support and information. That is one of the fantastic things I have seen on this forum that make it a truly valuable resource for those going through treatment with varying levels of liver disease and other compounding medical challenges. I have a profound respect for so many on here.

Good Luck. Jo

[nursehepc]

It is unfortunate that he communicated that he thought that this treatment was not seeming to work for you prior to knowing whether your viral load had decreased from your 4 week test or not (based on the increase in your ALT/AST). I am glad you have another consult hepatologist that you can rely on if necessary.

I am also thrilled that so many folks on the forum who have faced extreme challenges that

[zarmar]

Oh Kim - What a fantastic and wondrous difference prayers and good wishes make!  When I saw my hepatologist last week, he based his dire prediction on my status on not being UND in wk 4 and wk 8 uptick in LFT solely - I didn't know that he hadn't yet reviewed the PCR for wk 8.  Praises be - PCR was posted to me today, and I am UND -- what a truly beautiful number 0 is.  I am thrilled.  I had been knocked to the ground last week.  If I didn't already have my last 4 wk course of meds, my doctor said he might have taken me off the rest of Tx.  I know this is a very costly Tx.  I could accept that if it isn't effective for my purposes, and since better treatments are soon to be approved, my doctor might have started stepping back from me continuing.  However, he couldn't yet have known if it was effective for me.  He based his negative assessment to date on my not being UND at wk 4, and the increase in ALT/AST in wk 8.  This resulted in an entirely unnecessary anxiety attack. I am so fortunate to have a consult hepatologist at Mount Sinai who was a study clinician for trials of Sov.  I saw her for Tx input and review of my health profile last year before Sov was being prescribed.  She has been accessible to me without fail throughout Tx here in PA even though she is isn't my Tx physician. This may change for next Tx course if one is needed.

[Livelife777]

Sounds as tho you are in capable hands.   On a side line wanted to mention let your intuition be your guide.  In my life given dismal prognosises, my inner voice or intuition has never steered me wrong.  Sounds as tho deciding to seek answers at Mount Sinai, was a smooth move.  
As we are all aware Hector is our voice in overcoming this dreaded disease.
Believe his guidance is monumental in helping you to achieve SVR.  Along with that, we will also partner with him to help you thru.
Take care
...Kim

[zarmar]

Per your response - I live in Pittsburgh and am being treated at the Center for Liver Disease which includes the Starzl Transplantation Institute.  I have felt something that I can't quite put my finger on, but it motivated me to seek a second opinion with a hepatologist at Mount Sinai.  She has been great - I send her an email question and she replies usually same day.  I am not her Tx patient, but I feel she is fully engaged nonetheless.  She championed adding the Ribi to the 12 wk. protocol, but my local Hepatologist was concerned about my neutropenia, PTT, low WBC, etc.  He received approval for the off-label combo for me instead.  I also have a similar arrangement with consulting hematologist at Cornell Weill/New York Presbyterian.  I am currently treating/monitoring the NHL here.  Like you, I will travel wherever is best.  I am going back to the consult doctors in NYC in Aug. when I finish 12 wk Sov/Oly to assess.   I appreciate your support and excellent counsel.  Stay well.

[Livelife777]

When you have a strong team behind you, mountains can literally be moved.
The impossible becomes possible.  I am truly amazed and humbled by the effort of so many good souls willing to be there to help you.  I sincerely and honestly say that you can beat this.  In writing to you I wanted to convey that there is hope, and that all you need is a good team helping you thru it.  Please keep the faith...
...Kim

[HectorSF]

There are of course circumstances that may necessitate immediate therapy initiation in patients with milder histologic disease, such as those who have significant extrahepatic manifestations of HCV infection (such as membranoproliferative glomerulonephritis). In addition, some patients do not wish to defer, regardless of disease severity. In my practice, these individuals are offered either peginterferon, ribavirin, and sofosbuvir or simeprevir plus sofosbuvir, if available to them. It is estimated that there are at least 500,000 individuals with advanced fibrosis in the United States, and it is this group that represents the highest priority for initiating therapy now. However, those with genotype 1 HCV will likely have FDA-approved all-oral therapies available to them by the end of 2014, with SVR rates that could not have been imagined 5 years ago.
-----------------------------------------------------------------------------------------------
Do you have the Q80K polymorphism?
Just from this article the addition of ribavirin possibly at a lower dosage (as someone else mentioned) may be enough to get you undetectable. You don't mention being anemic but if you were to become anemic you could take Procrit to help stabilize the anemia as well as the addition of Neupogen for your WBCs. Many of us transplant patients needed these meds when we treated with interferon based treatments in past years in addition to blood transfusions some times. Of course all of this depends upon the severity of your cirrhosis and the risk of worse decompensation or liver failure although the risk is comparably very low in these none interferon based treatments.
Of course your hepatologist is the expert of your particular situation.

Cheers!
Hector

[HectorSF]

Although your situation isn't covered in this article Dr. Kwo covers all of the latest data (as of May) using new treatment that will be available in the next year. He does an excellent job of comparing SVR rates among various treatments and their use in cirrhotics.
--------------------------------------------------------------------------------------------------------
Reconsidering Whether to Treat Genotype 1 HCV Patients or Wait for All-Oral Therapy

• Thursday, May 15, 2014

Post-EASL Update:
Reconsidering Whether to Treat Genotype 1 HCV Patients or Wait for All-Oral Therapy
Paul Y. Kwo, MD

At the recent 2014 meeting of the European Association for the Study of Liver Disease (EASL) in London, extraordinary data were presented from large phase III trials involving the direct-acting antiviral (DAA) combinations of sofosbuvir plus ledipasvir and ABT-450/ritonavir plus ombitasvir and dasabuvir, each administered with and without ribavirin. Sustained virologic response (SVR) rates > 94% were reported with use of fixed-dose sofosbuvir/ledipasvir with or without ribavirin in genotype 1 treatment-naive patients and treatment-experienced patients (including protease inhibitor–exposed patients), including high SVR rates among the subsets of patients with CIRRHOSIS. Similarly, the combination of fixed-dose ABT-450/ritonavir/ombitasvir with dasabuvir and ribavirin resulted in SVR rates > 95% in trials for treatment-naive and treatment-experienced patients, and > 90% in a trial for CIRRHOTIC patients. In addition, small phase II studies demonstrated high SVR rates with the use of sofosbuvir/ledipasvir in HCV/HIV-coinfected patients, and with use of ABT-450/ritonavir/ombitasvir plus dasabuvir and ribavirin in patients with recurrent HCV infection following orthotopic liver transplant. These high SVR rates were achieved without the addition of interferon, the backbone of hepatitis C therapy for the past 2 decades. These investigational therapies are expected to be approved by the FDA before the end of 2014. Clinicians will then be able to offer all-oral therapies for patients across all HCV genotypes with the expectation of high SVR rates.

In the United States, high SVR rates can currently be achieved in genotype 1 HCV–infected patients who are treatment naive and interferon eligible with the use of peginterferon, ribavirin, and sofosbuvir. This combination resulted in an overall SVR rate of 89% with a 12-week treatment course in the phase III NEUTRINO study. For patients who have been treated previously with peginterferon/ribavirin and those who are interferon ineligible, the combination of sofosbuvir and simeprevir with or without ribavirin has been recommended as a therapeutic option in the 2014 AASLD/IDSA treatment guidelines based on high SVR rates demonstrated in the phase II COSMOS study.

How I’m Currently Managing Genotype 1 Patients
In my practice, all genotype 1 patients are candidates for therapy at this time, although histologic disease severity strongly guides my treatment recommendations. For genotype 1 patients, we offer peginterferon, ribavirin, and sofosbuvir as first-line therapy, but we strongly encourage patients to consider waiting for the all-oral regimens that are likely only months away from FDA approval, particularly those individuals with mild disease (F0-F2) in whom deferral of therapy is unlikely to lead to adverse clinical outcomes. Given the phase III data that have been presented, I find that virtually all patients with milder disease wish to defer therapy in order to have the opportunity to achieve SVR without interferon. Moreover, patient monitoring is significantly less complicated without use of interferon, even with the shorter treatment courses currently recommended for genotype 1 patients. This approach also applies to patients with milder disease (F0-F2) who have previously failed treatment.

By contrast, patients with advanced fibrosis, including those with F3/F4 fibrosis, are given the option of receiving therapy now. These individuals require careful assessment of the degree of advanced fibrosis as they are at risk for decompensating and are also screened regularly for hepatocellular cancer. In a subanalysis of the phase III NEUTRINO study, high SVR rates were reported across all degrees of fibrosis following treatment with 12 weeks of sofosbuvir, peginterferon, and ribavirin, with patients having proven histologic CIRRHOSIS by biopsy demonstrating an SVR rate of 78% whereas those with F3 fibrosis demonstrated an SVR rate of 89%. By historical standards, these are excellent SVR rates but are still numerically lower than rates reported from recent phase III all-oral therapy trials. After careful assessment, if I am confident that a patient’s fibrosis level is F3, I can tell them that they can safely defer therapy if they wish and that they will be followed closely, or they are offered peginterferon, ribavirin, and sofosbuvir or simeprevir with sofosbuvir, if available to them.
*****************************************************************************
In my practice, patients with CIRRHOSIS are all offered therapy. The phase II COSMOS study demonstrated high SVR rates with 12 weeks of sofosbuvir plus simeprevir with or without ribavirin in patients with F3/F4 fibrosis (94% to 100% in F3 fibrosis and 86% to 91% in F4) in both treatment-naive patients and null responders, and this is my preferred regimen in this population given the numerically higher SVR rates, regardless of whether the patient can tolerate interferon or not. In the COSMOS study, relapse was only seen in patients with genotype 1a HCV, of whom 2 of 3 relapsers had the Q80K polymorphism that is present in almost one half of genotype 1a individuals in North America and reduces susceptibility to simeprevir. Therefore, in genotype 1b patients, I recommend sofosbuvir plus simeprevir, and in patients with genotype 1a, I recommend sofosbuvir plus simeprevir with ribavirin. This option is particularly beneficial in patients with greater degrees of advanced fibrosis and portal hypertension, who are less likely to tolerate interferon, and in whom the CUPIC cohort study recently demonstrated that platelet count < 100,000/mm3 and albumin < 3.5 g/dL were associated with a significant risk of decompensation and/or severe infections.
*********************************************************************************
Continue....

[zarmar]

Thank you, thank you,  The two-timing from our own body chemistry is rough.  I am so encouraged by your experience.  

[zarmar]

Thank you, Pat.  An excellent reminder about the prize we are after-- UND at wk 4 or 8 isn't it.  I am far from done yet!

[zarmar]

I will post numbers later today and a longer response.  You are a life line to me.  I return to this forum every chance I get because this is the best place for invaluable support and solid content.  The cirrhosis seemed to happen so quickly along with the cancer diagnosis.  My last liver biopsy in 2010 was unremarkable, and then all the stuff hit the fan last year.  I have been trying to sort out implications from having two overlapping, as well as separate in terms of Tx, life threatening illnesses. The HCV community is so informed, understands the emotional aspect of the beast we all battle, and the sources for solid information that I don't find comparable on the cancer forums I visit.  We are fighters, and we will never give up, never give up, never give up.  Thank you for all you do.

[zarmar]

Hector  - I was so hoping I would hear from you.  I am crying a little now because you have helped me focus on right questions.  I'll take a minute to get back to normal level of overwhelmed, and respond back at length (I have had dry eye so long that when I can tear with real tears, it is good for my eyes!).

[zarmar]

I'll post my numbers later today, but the implication is the virus never left.  

[HectorSF]

Hi. I am sorry to hear of your very tough situation. You are caught between a rock and a hard place. But I think there is more hope and options than you may be aware of.

First, being undetectable by week 4 on Sovaldi & Olysio treatment has no effect on SVR rate. Many people that treat do not become undetectable by week 4. And less so if a person is not treating with the addition of Ribavirin. From the COSMOS trial.
" 85% of participants in the ribavirin-containing 12-week arm and 57% in the ribavirin-sparing 12-week arm achieved rapid virological response (RVR) at week 4."
" Rapid virologic response (RVR, defined as undetectable HCV RNA at Week 4 of treatment) was not found to be predictive of achieving SVR. In patients receiving simeprevir and sofosbuvir alone for 12 weeks, 93 percent achieved SVR, while 57 percent achieved RVR. "

Here at my transplant center we seen patients who have not been undetectable even by week 8 achieve SVR. So all hope is not lost. But additional help in getting undetectable by week 12 appears warranted. Of course the addition of Ribavirin would be the first choice but from what you say that may be contraindicated due to your poor synthetic liver function. But there may be other options as well.

You say you have ESLD. Have you been diagnosed with Childs-Pugh Class B cirrhosis? Decompensated?

Tonight at the presentation titled "Transforming HCV Management in the Pretransplant and Posttransplant Settings: The Role of New Agents" here in San Francisco we saw the results of a recent study which showed that Child-Pugh Class B cirrhotics had much longer times to become undetectable than Class A cirrhotics. Part of the discussion was what to do to get a patient undetectable.

In the discussed case before a patient's transplant so they have a good chance of not developing post transplant recurrence of hep C. But the same approach would apply to your own situation. How can we reduce the viral load to undetectable using current or new drugs that will soon be available.
------------------------------------------------------------------------------------------------
"Transforming HCV Management in the Pretransplant and Posttransplant Settings: The Role of New Agents"
Welcome and Introduction
Norah Terrault, MD, MPH
Director of Viral Hepatitis Research in Liver Transplantation
University of California San Francisco

Key Challenges in HCV Management in the Transplant Setting
Jean C. Emond, MD - Liver Transplant Surgeon
New York-Presbyterian Hospital/ Columbia University Medical Center

Interferon-Free HCV Therapy in the Transplant Setting
Paul Y. Kwo, MD
Medical Director of Liver Transplantation
Indiana University School of Medicine

Two Case Discussions: Redefining Best Practices in HCV Management in the Transplant Setting
Moderator: Norah Terrault, MD, MPH
Panel: Jean C. Emond, MD, and Paul Y. Kwo, MD

Question and Answers and Closing Remarks
Norah Terrault, MD, MPH

Norah is my hepatologist. She has managed my hep C, liver disease, liver cancer and recent transplant and upcoming hep C treatment.
------------------------------------------------------------------------------------------------------
As you are aware you are in a unique situation where your options are limited by not having liver transplant as an option. If I were you I would have your hepatologist contact Dr. Paul Y. Kwo,  Medical Director of Liver Transplantation, at Indiana University and get his ideas.
[phone] | Fax: [phone]
Email: ***@****
He is a leader, if not THE leader in the study all of the new non-interferon hep C drugs available now and those that will be available in the next few years and has been involved in many of the trials and the data surrounding the trials.

One option is that you may be eligible for "compassionate use" of Daclatasvir or AbbVie drugs that will be available later this years or early next year. I wouldn't leave any stone unturned.

"can-do-man" who is a great person on this forum had Dr. Kwo as his heptologist. He may be able to tell you how best to contact him. I will write can-do and make sure he is aware of our conversation and my suggestion for your hepatologist to consult with Dr. Kwo..

I was in a similar situation myself late year when I had run out of standard protocol options and my liver cancer was beyond listing criteria so I was ineligible for the only cure for my liver cancer (HCC), liver transplant. I volunteered for an experimental radiation cancer treatment which miraculously worked allowing me to be alive today.

I hope you find this helpful. At least we can help you take care of you hep C and liver disease issues then you will be able to focus your attention on overcoming you cancer. One step/battle at a time is how we move forward.

"if I would be approved for insurance coverage"
Don't even worry about that. That is down the road. You have enough on your plate right now. You will get the meds you need.  

Hang in there. Stay hopeful. That is the one thing we do have some control over.
Let me know that I can do to help.

If I can get the PowerPoint Slides or discussion from tonight's presentation I will post them for you. Right now I only have my own notes related to my own hep C/transplant issues and some issues a few friends have.
Hector

[Livelife777]

I can so relate to your situation as well, as I know unfortunately alot about cancer.  Actually am a 2Xs cancer survivor, and I'm not talking about the skin.  Have had 2 separate primary's 10 years apart and have gone down the chemo road on more then 1 occasion.  At present I am NED ( no evidence of disease )
Aside from this I have early cirrhosis and was placed on the transplant list at Mayo Clinic.  Wanted to give you some hope, as I understand what being defeated feels like.  Might also add that I have been removed from the transplant list, since my liver is showing signs of regeneration mainly due to the elimination of the Hep C virus.   This is what you need to accomplish to keep your liver healthy and functioning.
You said that you are in partial remission.  To get on the list if need be, you need to obtain complete remission.  The new immunotherapy at present is impressive, but amazing new strides in Tx are closer then we can imagine.
I don't know where you are receiving Tx, but at the major comprehensive cancer centers many with Lymphoma are being cured.   Not sure if you've looked into any clinical trials, but they have been having great success with blood cancers.  I bring this up, as I feel soon, you will be able to be a transplant candidate if need be.  Please know that some of the dismal %s of the past, are now experiencing a shift towards wellness.
Because you are in a vicarious situation with your liver, its important that you find a hepatologist whom deals in special populations.  Meaning one in which is familiar with many aspects of liver disease.  It is really imperative for you to find the best, and also cure your Hep C.  Usually these Drs are associated with a teaching hospital as they tend to be ahead of the curve.  I don't know where you live, but you could google to find the closest in your area.  On a side note we are kinda in the same boat and I do travel for my Tx, as I know how important it is for the best outcome.
Guess what this lengthy story means is that you can cure your Hep C.  There are many others out there like us, that have to walk the extra mile, but we do make it to the finish line.  In summation, find the best specialist you can, and have faith that you will overcome these obstacles.  
Be well, and take care
...Kim