Good news...
----------
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
Thanks for posting the article.