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Post Transplat patients
Good news...
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Are New HCV Therapies Ready for Use in Transplant Patients?
Paul Y. Kwo, MD - 7/10/2014 More from this author
December 2013 marked the first drug approval from a new class of direct-acting antiviral (DAA) agents, the nucleotide polymerase inhibitors. Sofosbuvir was approved for use in combination therapy both with and without interferon. For genotype 1 patients, clinical trials demonstrated overall SVR rates of 90% when sofosbuvir was combined with peginterferon and ribavirin for 12 weeks and 70% SVR rates when sofosbuvir was given with ribavirin for 24 weeks. For genotype 2 and 3 patients, SVR rates were more than 85% with the interferon-free combination of sofosbuvir and ribavirin for 12-24 weeks. In addition, the approval of a once-daily protease inhibitor simeprevir has allowed clinicians to remove interferon and ribavirin from the equation in genotype 1 infection by combining sofosbuvir and simeprevir for 12-24 weeks; a regimen associated with SVR rates > 90% in genotype 1 individuals.
The Arrival of DAA Therapy in the Pretransplantation Setting
The prescribing information for sofosbuvir also included an indication for use in the pretransplantation setting when combined with ribavirin for cirrhotic patients with hepatocellular carcinoma, who meet Milan criteria. The regimen is given and virus suppressed for up to 24-48 weeks in an effort to eradicate virus prior to transplantation and prevent reinfection of the graft after transplantation. In our pretransplantation clinic, we are now able to suppress HCV viremia prior to transplantation with sofosbuvir and ribavirin in those with mild decompensation or with hepatoma. Whether suppression prior to transplantation will be the best strategy remains to be seen as it is not always possible to predict the timing of transplantation, especially without living related transplants. However, most patients we have treated tolerate this approach well, and we are noting that some patients have experienced clinical improvement that has allowed them to come off
the transplantation list. Certainly longer-term follow-up will be required to see if this trend continues. I am interested to see if this approach can be applied to individuals who require orthotopic liver transplantation without hepatocellular carcinoma and who have Child-Turcotte-Pugh scores greater than 7; data evaluating this approach are still needed.
Interferon-Free Options in Posttransplantation Patients
The phase II COSMOS study combining sofosbuvir with simeprevir (without interferon or ribavirin) has demonstrated that SVR may be achieved in traditionally difficult-to-treat patient populations, including those with previous null response to peginterferon and ribavirin as well as those with F3 or F4 fibrosis. Although there are few data currently evaluating this regimen after transplantation, neither sofosbuvir nor simeprevir have meaningful drug–drug interactions with the calcineurin inhibitors tacrolimus and cyclosporine, and therefore, our center and others are now combining these 2 direct-acting antivirals after transplantation. We have found this gives genotype 1 HCV–infected posttransplantation patients a treatment option that removes agents that were difficult to tolerate due to the immunosuppression and poor tolerance of cytopenias.
Sofosbuvir combined with ribavirin is another option after transplantation that has demonstrated SVR rates of more than 70% in one study and, in another study, has shown efficacy as a salvage strategy for those with the dreaded complication of fibrosing cholestatic hepatitis C.
The combination regimen of ABT-450/ritonavir/ombitasvir plus dasabuvir and ribavirin, which is expected to become available for the treatment of HCV infection later this year, has also been evaluated in genotype 1 HCV liver transplantation recipients with recurrent infection. Among evaluable patients at the time of interim analysis, 96% had achieved SVR. Alterations in calcineurin inhibitors were required but were manageable.
These findings make me believe that the future for patients with advanced liver disease and posttransplantation hepatitis C infection is indeed bright. In fact, I think it is likely that with successful eradication of hepatitis C with therapies that are well tolerated, the hepatitis survival for orthotopic liver transplant for hepatitis C will match survival in those who are not HCV infected.
http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/London%202014/Clinical%20Thoughts/CT%201.aspx
----------
Are New HCV Therapies Ready for Use in Transplant Patients?
Paul Y. Kwo, MD - 7/10/2014 More from this author
December 2013 marked the first drug approval from a new class of direct-acting antiviral (DAA) agents, the nucleotide polymerase inhibitors. Sofosbuvir was approved for use in combination therapy both with and without interferon. For genotype 1 patients, clinical trials demonstrated overall SVR rates of 90% when sofosbuvir was combined with peginterferon and ribavirin for 12 weeks and 70% SVR rates when sofosbuvir was given with ribavirin for 24 weeks. For genotype 2 and 3 patients, SVR rates were more than 85% with the interferon-free combination of sofosbuvir and ribavirin for 12-24 weeks. In addition, the approval of a once-daily protease inhibitor simeprevir has allowed clinicians to remove interferon and ribavirin from the equation in genotype 1 infection by combining sofosbuvir and simeprevir for 12-24 weeks; a regimen associated with SVR rates > 90% in genotype 1 individuals.
The Arrival of DAA Therapy in the Pretransplantation Setting
The prescribing information for sofosbuvir also included an indication for use in the pretransplantation setting when combined with ribavirin for cirrhotic patients with hepatocellular carcinoma, who meet Milan criteria. The regimen is given and virus suppressed for up to 24-48 weeks in an effort to eradicate virus prior to transplantation and prevent reinfection of the graft after transplantation. In our pretransplantation clinic, we are now able to suppress HCV viremia prior to transplantation with sofosbuvir and ribavirin in those with mild decompensation or with hepatoma. Whether suppression prior to transplantation will be the best strategy remains to be seen as it is not always possible to predict the timing of transplantation, especially without living related transplants. However, most patients we have treated tolerate this approach well, and we are noting that some patients have experienced clinical improvement that has allowed them to come off
the transplantation list. Certainly longer-term follow-up will be required to see if this trend continues. I am interested to see if this approach can be applied to individuals who require orthotopic liver transplantation without hepatocellular carcinoma and who have Child-Turcotte-Pugh scores greater than 7; data evaluating this approach are still needed.
Interferon-Free Options in Posttransplantation Patients
The phase II COSMOS study combining sofosbuvir with simeprevir (without interferon or ribavirin) has demonstrated that SVR may be achieved in traditionally difficult-to-treat patient populations, including those with previous null response to peginterferon and ribavirin as well as those with F3 or F4 fibrosis. Although there are few data currently evaluating this regimen after transplantation, neither sofosbuvir nor simeprevir have meaningful drug–drug interactions with the calcineurin inhibitors tacrolimus and cyclosporine, and therefore, our center and others are now combining these 2 direct-acting antivirals after transplantation. We have found this gives genotype 1 HCV–infected posttransplantation patients a treatment option that removes agents that were difficult to tolerate due to the immunosuppression and poor tolerance of cytopenias.
Sofosbuvir combined with ribavirin is another option after transplantation that has demonstrated SVR rates of more than 70% in one study and, in another study, has shown efficacy as a salvage strategy for those with the dreaded complication of fibrosing cholestatic hepatitis C.
The combination regimen of ABT-450/ritonavir/ombitasvir plus dasabuvir and ribavirin, which is expected to become available for the treatment of HCV infection later this year, has also been evaluated in genotype 1 HCV liver transplantation recipients with recurrent infection. Among evaluable patients at the time of interim analysis, 96% had achieved SVR. Alterations in calcineurin inhibitors were required but were manageable.
These findings make me believe that the future for patients with advanced liver disease and posttransplantation hepatitis C infection is indeed bright. In fact, I think it is likely that with successful eradication of hepatitis C with therapies that are well tolerated, the hepatitis survival for orthotopic liver transplant for hepatitis C will match survival in those who are not HCV infected.
http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/London%202014/Clinical%20Thoughts/CT%201.aspx
THis is very encouraging news. I think I would belive anything Dr. Kwo says. He is one of my heros.
Hector - my good vibes are headed your way with regard to starting treatment again. Third time is a charm
bean
Hector - my good vibes are headed your way with regard to starting treatment again. Third time is a charm
bean
Can-do, I didn't know that Dr. Kwo was your hepatologist. Excellent! He is one of the very best.
I hope to meet him when he is here in San Francisco at the symposium. My UCSF hepatologist Norah Terrault will be the introducing him and Dr. Emond from NewYork-Presbyterian/Columbia and she will moderating the discussion on transplantation and hepatitis C.
Dr. Kwo's talk with be titled "Interferon-Free HCV Therapy in the Transplant Setting". Dr. Emond will give a talk titled "Key Challenges in HCV Management in the Transplant Setting" and then they will have a case discussion redefining best practices in the transplant setting.
I will be starting treatment again (#3) with Norah at the end of August with Sovaldi, Olysio and ribavirin.
Be well!
Hector
I hope to meet him when he is here in San Francisco at the symposium. My UCSF hepatologist Norah Terrault will be the introducing him and Dr. Emond from NewYork-Presbyterian/Columbia and she will moderating the discussion on transplantation and hepatitis C.
Dr. Kwo's talk with be titled "Interferon-Free HCV Therapy in the Transplant Setting". Dr. Emond will give a talk titled "Key Challenges in HCV Management in the Transplant Setting" and then they will have a case discussion redefining best practices in the transplant setting.
I will be starting treatment again (#3) with Norah at the end of August with Sovaldi, Olysio and ribavirin.
Be well!
Hector
Thanks for the info. If offers hope for some of us on the transplant list that if we kill the virus our livers might improve enough to no longer need a transplant. I am on week 25 of Sovoldi and riba. 4 months after RFA for my HCC tumor I still have no recurrence of the Tumor or any new tumors. My plan is to go 48 weeks and hope for SVR . Its a long shot but who knows maybe I can avoid a transplant.
Doctor Kwo is one of many that is tops in his field. Not only is he my doctor he listens and will take advice from his patients. And a great teacher. Anyone from Indiana would be very fortunate to have him as their doctor.
I agree one day soon even folks like your husband will be free of this. Best to both of you.
I agree one day soon even folks like your husband will be free of this. Best to both of you.
Great article. Thank you for sharing it. The author, Dr. Kwo, is apparently an excellent MD and will be presenting at a symposium on July 28 in San Francisco entitled "Transforming HCV Management in the Pretransplant and Posttransplant Settings: The Role of New Agents".
https://www.regonline.com/Register/Checkin.aspx?EventID=1575655
As the caregiver of someone who has been fighting recurrent Hep C for two years now (post transplant), it gives me great hope that one day soon he too will finally be free of this insidious monster virus.
Nan
https://www.regonline.com/Register/Checkin.aspx?EventID=1575655
As the caregiver of someone who has been fighting recurrent Hep C for two years now (post transplant), it gives me great hope that one day soon he too will finally be free of this insidious monster virus.
Nan
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Thanks for posting the article.