Inmaculada Fernández1, Raquel Muñoz-Gómez2, Juan M Pascasio3, Carme Baliellas4, Natalia Polanco5, Nuria Esforzado6, Ana Arias7, Martín Prieto8, Lluis Castells9, Valentín Cuervas-Mons7, Olga Hernández2, Javier Crespo10, José L Calleja11, Xavier Forns12, María-Carlota Londoño12. 1. Digestive Disease Service, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: ifvazquez@salud.madrid.org. 2. Digestive Disease Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Digestive Disease Service, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, Spain. 4. Digestive Disease Service, Liver Transplant Unit, Hospital Universitari de Bellvitge IDIBELL, Barcelona, Spain. 5. Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Nephrology Department, Hospital Clinic Barcelona, Barcelona, Spain. 7. Internal Medicine Hospital Universitario Puerta de Hierro, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain. 8. Liver Unit, Digestive Medicine Service, Hospital Universitari i Politecnic La Fe, CIBERehd, Valencia, Spain. 9. Liver Unit Internal Medicine Department, Hospital General Universitari Vall d' Hebron, CIBERehd, Barcelona, Spain. 10. Gastroenterology and Hepatology Unit. Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain. 11. Liver Unit, Hospital Universitario Puerta de Hierro, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain. 12. Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Abstract
BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.
BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.
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