Nonresponder or treatment experienced?

[nan535]

How is my husband classified?

He was on triple treatment with Incivik for 5 weeks and had to stop due to really bad side effects.
Despite the short time he was on treatment, he remained undetected for the virus for 8 months until he had a transplant. The virus then reappeared.

My guess is treatment experienced.  I think had he been able to complete his treatment he might well
have achieved SVR.

Nan

[nan535]

I've been thinking about your posts. I was wondering what you think about my husband's chances for SVR12 with this combo (Solvaldi plus Ribavirin) for 24 weeks given that you relapsed after a month after taking it for 48 weeks.( My husband is Geno 1a).

I don't think there is another option for him at this time so if the treatment is made available to him in January as expected, he will do it. I'm thinking at worst, if he has a similar response to it as you had (i.e. undetected for 48 weeks before relapsing) it may at least get him further down the road toward a treatment that will work for him.

I am not being pessimistic. Having been through so much already, I just like to think about all the possibilities before they happen so we can know we have a Plan B if not successful.

Nan

[nan535]

Just wanted to add this which I found in looking over the links you provided.
See the video included.

http://hepatitiscresearchandnewsupdates.blogspot.com/2013/11/video-sofosbuvir-ribavirin-therapy.html

Thank you again for steering me in the right direction for information of this treatment for post transplant patients.
Nan

[nan535]

Thank you so much for this information. You are an amazing person. You are in the middle of your own recovery from transplant and yet you find the time to do the research for a total stranger. God knew what he was doing when he helped the doctors to find a way to save your life. You have more work to do here.  

My husband's recent labs show total bilirubin at 2.9 (normal range 0.1-1.2), His ALK Phos is very high at 473  (normal range 30-110). His AST is at 101  (normal 1-50),  He does not have ascites at present but the encephalopathy he is prone to, requires daily doses of lactulose and 550 mg Xifaxin to keep him stable. though ALT is in normal range at 34.

Of the information you provedid above this is what particularly stood out given my husband's condition:

"The clinical condition of 32 of the 45 patients (71%) rapidly improved according to investigators’ narratives (eg, normalization of ALT and/or bilirubin levels, resolution of ascites which had been refractory to diuretics or requiring paracentesis, resolution/improvement of encephalopathy, increased muscle mass) within 1-4 weeks after the start of treatment. "

I am now very much looking forward to his starting treatment.  God willing it will help him to improve and resolve these conditions also.

I will let you know how he does.

Thank you again! It definitely has given us much needed hope.
Nan

[HectorSF]

Nan,

Here is the complete data from the study "Sofosbuvir/Sovaldi Compassionate Use Program" with graphs...

64rd Annual Meeting of the  American Association for the Study of Liver Diseases (AASLD) Washington, DC Nov 1-5 2013

"Initial Evaluation of the Sofosbuvir Compassionate Use Program for Patients With Severe Recurrent HCV Following Liver Transplantation"

Reported by Jules Levin

Presented at The Liver Meeting 2013: 64th Annual Meeting of the American Association for the Study of Liver Diseases, November 1-5, 2013, Washington, DC

Xavier Forns,1 Robert J. Fontana, 2 Dilip Moonka, 3 John G. McHutchison, 4 William T. Symonds, 4 Jill Denning, 4 Lindsay McNair, 4 Paul Chang ,4 Valerie Kivett, 4 Mitchell L. Shiffman,5 Michael Charlton 6

1 Liver Unit, Hospital Clinic, Barcelona, Spain;
2 University of Michigan, Ann Arbor, MI;
3 Henry Ford Health System, Detroit, MI;
4 Gilead Sciences, Inc., Foster City, CA;
5 Liver Institute of Virginia, Richmond, VA;
6 Mayo Clinic, Rochester, MN

http://www.natap.org/2013/AASLD/AASLD_29.htm


I hope this helps and give you both hope!
Best
Howie

[HectorSF]

Nan,

Myself, as a genotype 1b patient treated with Sovaldi and Ribavirin for 48 weeks pre-transplant so I am very familiar with the treatment myself. I was I was a previous NULL-RESPONDER to peg-interferon and Ribavirin but with the Gilead treatment I WAS UNDETECTABLE ONLY ONE WEEK AFTER STARTING TREATMENT starting the treatment and was undetectable throughout the rest of the 47 weeks of treatment. Unfortunately Gilead would let me treat longer than 48 weeks so I had to stop treatment before my transplant and the virus returned in about a month and I went into transplant with active hep C. The purpose for the study was for us to be treating with the two drugs and being undetectable at transplant and see how many of us would not have recurrent HCV post transplant.

I am still very happy that I did the treatment as I believe it stopped the virus from destorying my liver for almost a year and allowed me to have enough liver function so that I could still have my liver treated for cancer 6 times this year and have the 6th treatment work to get me back on the waiting- list and getting a transplant almost 4 weeks ago now.

Rarely, liver transplant recipients develop a particularly aggressive form of recurrence called “Fibrosing Cholestatic HCV infection” (FCH), in which patients have very high levels of HCV RNA, elevated bilirubin levels, and progressive fibrosis. It is hoped that direct-acting antiviral (DAA) agents may be able to slow progression of this condition by stopping HCV replication. Gilead has a compassionate use program for those suffering with this condition.

“SOF was provided in an IRB-approved compassionate use protocol (eIND or expanded access protocol) to treat patients with severe recurrent HCV infection following LT, including patients with fibrosing cholestatic hepatitis (FCH). The regimen included SOF 400 mg/day for up to 48 weeks, with appropriate doses of RBV and/or PEG at the physician’s discretion. Treating physicians provide periodic updates of clinical status, lab tests, and serious adverse events (SAEs).

“Results: As of APR2013, 115 patients have been approved for compassionate use and 63 have started treatment. Of these, 45 have received ≥4 weeks of a Sofosbuvir-containing regimen (36 SOF + RBV, 9 SOF+PEG/RBV). Baseline features of these 45 patients were: 33 GT1, 5 GT3, 7 other GTs; 29% female; mean age 55 years; mean baseline bilirubin 6.0 mg/dL (range 0.4-25.8) albumin 3.1 g/dL (2.0-4.8), INR 1.26 (0.96-2.07) and platelets 103 x 103/uL (27-316 x 103). Nineteen of the 45 (42%) had histologically-documented FCH. At week 4 of therapy, 28 of 36 patients (78%) who had reported HCV RNA levels were less than the limit of detection or quantification and 2 patients who received only 12 weeks of treatment have achieved SVR 12. The clinical condition of 32 of the 45 patients (71%) rapidly improved according to investigators’ narratives (eg, normalization of ALT and/or bilirubin levels, resolution of ascites which had been refractory to diuretics or requiring paracentesis, resolution/improvement of encephalopathy, increased muscle mass) within 1-4 weeks after the start of treatment. Another six patients (13%) were reported to have stabilized from their prior decompensation. Seven patients (16%) died after initiating therapy, with all deaths attributed to progression of liver disease or associated complications. Forty-seven SAEs have been reported in 23 patients. None were attributed to study drug.”

http://hepatitiscresearchandnewsupdates.blogspot.com/2013/11/initial-evaluation-of-sofosbuvir.html

I friend of mine with this form of aggressive HCV post transplant has been taking this treatment for a few months now and I believe it has helped to stabilize his condition although he is still having issues with ascites and needs paracentesis every few weeks.

This treatment is the best hope that we have seen so many doctors are optimistic about its effectiveness.

I can't imagine what you and your husband must be going through. All I can say from my own experience is to always try to stay hopeful, that someway, somehow you both will get through this.

I wish you both my best!
Howie

[nan535]

Unfortunately my husband has not been so lucky. He developed post transplant complications (hepatic artery blockage which led to a damaged bilary tree).  A liver biopsy last week shows his new donor liver now has cirrhosis (only a year and a half after transplant). Pathologist blames it half on the bile duct obstructions and half on the Hep C recurrence. He is again having bouts of hepatic encephalopathy which is so debilitating as you may know.

His transplant center plans to start him on Sovaldi in combination with Ribavirin for 24 weeks sometime in January.  Hopefully he will be up to the challenge.  

The reason I asked what he would be considered - a null responder or treatment experienced- is I was looking at the trial results listed and wondering what his chances for success will be.  

You are right I'm sure. Being a transplant recipient puts him in a very different
place.  His doctor told us they are very excited at the possibilities going forward with this new medicine.  I guess we just have to hope and pray that it will be enough to help him.

Thanks and all the best in your continuing recovery.

Nan

[HectorSF]

Technically he is treatment experienced but it should have little to no effect on his future treatment unless he will be treating soon.

Treating hep C post transplant is very different than treating it pre transplant. Many of the rules that apply to people without transplants don't apply. We are different people then when we last treated. We have another liver, not ours that we last treated with. We are immune suppressed and taking many meds some that could interact with the treatment drugs. Only the transplant center can assess if and when a patient with recurrent hep C should be treated post transplant and what treatment would be most effective for him.

I also was transplanted 3 weeks ago having active hep C. Unfortunately we don't have the data as yet from Gilead as to how well Sovaldi works in post transplant patients. I am hoping we get good news on that front in 2014. The new treatments coming from now on can't be anything but good for us. Before with peg-INF and Ribavirin SVR rates were only about 30% in post transplant genotype 1s. Three drug treatments have had very serious side effect issues in post transplant patients So new treatments is were out hope lays.

I am also hopeful that my new liver can fight the hep C to prevent it from harming my precious donor liver. Not everyone needs hep C treatment post transplant even though they are infected.

Congratulations on the transplant! Here is to our new lives!!!
Hang in there. Having overcome the challenges of advanced liver disease and/or liver cancer we will beat this hep C once and for all!
Hector