Recurrent HCV and HCV Treatment

[HectorSF]

Amazing study results for post liver transplant patients with recurrent hepatitis C!

M12-999 Study: Preliminary Results Reveal Very High Efficacy With ABT-450/RTV/Ombitasvir + Dasabuvir and Ribavirin in Liver Transplantation Recipients With Recurrent Genotype 1 HCV
http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/London%202014/Highlights/Capsules/114.aspx

Source: 2014 Annual Meeting of the European Association for the Study of the Liver

M12-999: single-arm, open-label phase II study

Summary of Key Conclusions:

* 24 weeks of ABT-450/ritonavir (RTV)/ombitasvir + dasabuvir + ribavirin highly efficacious in immunosuppressed liver transplantation recipients with recurrent genotype 1 HCV
* 96% of evaluable patients attained SVR12
* No virologic breakthrough observed
* 3 direct-acting antiviral regimen well tolerated
* Low rate of treatment discontinuation due to adverse events (AEs) (1 patient)
* No deaths, graft loss, or rejection episodes
* Calcineurin inhibitor dose reduction necessary, but manageable

Study Design:

All patients received ABT-450/RTV/ombitasvir + dasabuvir + ribavirin for 24 weeks
ABT-450/RTV/ombitasvir 150/100/25 mg once daily
Dasabuvir 250 mg twice daily
Ribavirin dose managed at discretion of treating physician
Dosing of calcineurin inhibitors based on phase I pharmacokinetic study
Recommended tacrolimus dose modified to 0.5 mg once weekly or 0.2 mg every 3 days
Recommended cyclosporine dose modified to 20% of daily dose administered prior to study treatment
Patients followed to Week 72

Eligibility
Inclusion criteria
18-70 years of age
Chronic infection with genotype 1 HCV
Liver transplantation resulting from HCV infection within 12 months prior to screening
No HCV therapy after transplantation
Peginterferon/ribavirin use prior to transplantation permitted
METAVIR score ≤ F2, confirmed by liver biopsy
No previous steroid-resistant rejection
Receiving stable tacrolimus- or cyclosporine-based immunosuppressant regimen
Prednisone ≤ 5 mg/day permitted
No use of mTOR inhibitors

Main Findings

Very high SVR12 rates observed to date with ABT-450/RTV/ombitasvir + dasabuvir + ribavirin
No patient had virologic breakthrough
1 patient had virologic relapse at 3 days posttreatment, with emergent resistance associated mutations
NS3 mutation: R155K
NS5A mutations: M28T, Q30R
NS5B mutations: G554S, G557R
ABT-450/RTV/ombitasvir + dasabuvir + ribavirin safe and relatively well tolerated
No acute or chronic rejection episodes
1 patient discontinued treatment after Week 18 due to AEs (moderate rash, memory impairment, anxiety), but achieved SVR12
2 patients experienced serious AEs
Hypotension and tachycardia following tamsulosin initiation after elective surgery
Moderate peripheral edema and pain in extremity in diabetic patient with previous peripheral edema
Most common AEs included headache and fatigue

Other Outcomes

Ribavirin dose adjustment common during therapy
Most patients received ribavirin 600-800 mg/day at baseline and end of treatment
Prespecified tacrolimus and cyclosporine dose modifications appeared to be effective
Tacrolimus Ctrough levels similar pretreatment and on treatment (Weeks 1-4)
Most patients received tacrolimus 0.5-1.0 mg at 1- to 2-week intervals
4 patients had tacrolimus level > 15 ng/mL (range: 15.7-34.0)
All due to dosing errors
Subsequent creatinine elevation observed in 2 patients (1.4 and 1.8 mg/dL), which normalized following dose correction
Cyclosporine levels maintained within therapeutic range among 5 patients receiving this agent


Hector

[HectorSF]

Nan, as you know I did 48 weeks of this treatment (1,200 mg riba) under very different circumstances. The plus for your husband is at minimum extended treatment will provide more weeks of the hep C not beating up on his liver and possibly greater odds of SRV.

Of course that must be balanced with the impact of the anemia and other side effects. It is always a risk vs benefit situation. Only the patient and their caregiver can make that call as each of us assigns different values to those risks and benefits.

I can only hope that the both of you have a relationship with the doctor(s) so you are all working towards the same goal together. I think you probably do, which from my experience is how all of us can maintain our strength and hope despite the enormous challenges you are both facing. I admire you and your husband's tenacity and fight. I believe it strengthens all of us. As well as his doctors. It is an example for all of us. It definitely helps me to better face my own situation and I am very grateful for that.

“It’s not what is taken away that counts - it's what you do with what you have left."

Best -
Howie

[nan535]

Thank you, Sunru. Yes that's the treatment I'm hoping he will be able to take if this one doesn't work out. It's tricky because he is post transplant with symptoms of decompensated cirrhosis. This treatment though difficult for him is at least preventing further decompensation and actually allowing his body to heal itself somewhat.  So hopefully when we get past this latest blip in the road, things will continue in a positive direction.

Thank you for your very kind wishes and prayers. Much appreciated.
Nan

[sunru]

I thought I read somewhere the Solvaldi/Ledipasvir one fixed dosed pill could be approved by the end of 2014 or early 2015????. Since he is gt 1a, it might be a good one for him to continue at some point.  

Please keep us posted on his condition, sending healing thoughts & prayers.
SunRu

[sunru]

Sounds like you are in a good place. It appears that physical suffering has it's rewards if one can see it that way.  

I recently was approved for ssd and should be eligible for medicare sometime around June 2015. Planning to try to get by as a kaiser member until I become eligible for medicare, although it has been more challenging then ever with kaiser lately. When I have medicare I plan to sign up with a PPO and gel lined up with UCSF. Lately, kaiser has been giving me a few second opinion referrals to Dr. Terrault.  I like her, she is no-nonsense and even though she doesn't have to say a word to me, I can tell she doesn't let my kaiser dr give her the run-around like he'd like to. He does it to me all the time. I'm at the place now where I feel I have to try to be compliant and ignore him to keep sanity until I can change plans. It has been extremely helpful to get clear information from Dr.T. and then request her recommendations to my kaiser dr. Well, you take care Howie and keep up the good work.

[nan535]

Thank you for your very kind words. They mean alot.
My husband is 1a.  His kidneys are rebounding very slowly.  My fear is that the Hep C meds are preventing them from rebounding as they should. i think the next week will tell the story. He did have to go off treatment one day since the protocol calls for a eGFR of 30. Because of the injury to his kidneys (caused by the IV antibiotic),  it dropped to 26.  Its now back up to 31 so he is back on treatment.  Very frustrating and upsetting because with the Hep C meds, his eGFR had risen to 58 before the injury.
For those who know it, the Apollo Greek myth comes to mind.

Nan

[HectorSF]

Frankly hep C is not a priority issue in my case. My hepatologist and myself discussed it before my transplant last November just so we were on the same page as far as recurrence post transplant and how we would approach it. So if and when I start hep C treatment is up to my hepatologist. She is one of the leaders in the field of hepatitis and liver transplant so I can be assured of the best possible treatment for myself whether the treatment is available on the market or in a trial.

Dr. Terrault is the one who got me into the Gilead trial that allowed the FDA to approve Sovaldi + ribavirin for patients with liver cancer (HCC) while awaiting transplant. I am very happy to have been one of the 61 people world-wide to have been in that trial almost 2 years ago now.

Right now I am the proud recipient of a 36 year old, female, stage 0 liver. I am exercising to stay in shape, eating healthier than ever and basically doing everything I can to keep my whole body as healthy as possible for as long as possible. I have no other medical issues currently so I am very, very lucky and so far, no post transplant complications except for minor medication issues.

Like all cancer patients, I live my life knowing that cancer could always be just around the next corner. I know everyday it is a miracle that I am even alive never mind as healthy as I am. I see each day is an opportunity to learn how to live life to the fullest.

Cheers
Howie

[sunru]

Thank you so much for best wishes Nan. I know how hard it must be for you. what a great support you must be for him(husband).  I know you are for so many on this forum as well.. What GT is he? can the kidneys be repaired?

[sunru]

Sounds like they're focusing on better tx options for pre-and post transplant. Very good news Howie. thanks for sharing. Hope U can get something like this going soon.  Abbvie should be approved this year? When will U start tx?

[nan535]

He is scheduled for  24 weeks of the Sovaldi/Ribavirin treatment but we were discussing with his doctor just today whether he might need to go even further that that. The guidelines suggest "up to 48 weeks" for this population. Given that it took 7 weeks to get to undetected, it may be prudent to extend his time on treatment.

All of his labwork shows improvement. It's quite amazing.

Nan

[HectorSF]

My take on this study is that things are improving in leaps and bounds for all folks with hep C even us post transplant folks who had few if any options post transplant only a year ago.

Yes, taking a handful pills seems crazy when Gilead will have one pill a day treatment later this year. And we know that ribavirin can cause anemia in persons with advanced illness though it is unusual in those with lesser liver disease. Only 10% in those taking Sovaldi and Ribavirin for 12 weeks. But for those with either advanced liver disease or post transplant.."We Do What We Have To Do". If I have to take a pill an hour I would do it to improve my health and well-being.

Gilead will be treating all classes of cirrhosis both pre and post transplant soon. We will learn a lot from that trial. The results will probably change post transplant hep C recurrence treatment profoundly.

It is very unfortunate that your husband developed fibrosing cholestatic hepatitis (FCH) post transplant. Luckily it is a very rare complication for transplant folks although that is of little solace to you and others that are suffering with it! We need  better treatments for FCH... ASAP!
My hope is that with all the progress being made in the understanding of hepatitis C and its treatment, we can find better solution for those suffering with aggressive hep C post transplant.

Maybe someday they might even be able to help us liver cancer post transplant folks. Unfortunately I think that is further off as cancer research has not advanced as rapidly as hepatitis C has.

Nan, Is your husband going to be treating for 12 or 24 weeks?
I am glad he is undetectable and I hope that is stopping further damage by his hep C.

Wishing you both my best!
Hector

[nan535]

Thanks for posting this new treatment information with a high cure rate.

I am disappointed to see that it includes Ribavirin. As you know my husband has been having a difficult time on treatment because of the procrit shots he gets weekly (to maintain his hemoglobin at 10 or above) for the first seven weeks. This has resulted in HE every week.  His doctor has agreed to stop the procrit shot for a while and see how it goes. His hemoglobin is at 8.8 and we will see if he can maintain it there. His ribavirin has been lowered to 200 mg. The good news is he is undetected for the virus though it took 7 weeks to get there.

So I'm not thrilled that this new treatment will require him to take ribaviriin.
Hopefully,other treatments are being studied now for post transplant patients that will not require ribavirin.

I do not want to discourage others about this new treatment. My husband is unique to say the least and his problems with ribavirin may not be norm for others.

Regards,
Nan