title: Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Digestive Disease Service, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: ifvazquez@salud.madrid.org.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Digestive Disease Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Muñoz-Gómez
authors.affiliation: Digestive Disease Service, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pascasio
authors.affiliation: Digestive Disease Service, Liver Transplant Unit, Hospital Universitari de Bellvitge IDIBELL, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Baliellas
authors.affiliation: Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Polanco
authors.affiliation: Nephrology Department, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Esforzado
authors.affiliation: Internal Medicine Hospital Universitario Puerta de Hierro, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arias
authors.affiliation: Liver Unit, Digestive Medicine Service, Hospital Universitari i Politecnic La Fe, CIBERehd, Valencia, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Prieto
authors.affiliation: Liver Unit Internal Medicine Department, Hospital General Universitari Vall d' Hebron, CIBERehd, Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Castells
authors.affiliation: Internal Medicine Hospital Universitario Puerta de Hierro, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Cuervas-Mons
authors.affiliation: Digestive Disease Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Hernández
authors.affiliation: Gastroenterology and Hepatology Unit. Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Liver Unit, Hospital Universitario Puerta de Hierro, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: María-Carlota
authors.initials: MC
authors.lastname: Londoño
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007165:Immunosuppression Therapy; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D013030:Spain; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007372:Interferons
keywords: Direct-acting antivirals; Hepatitis C; Immunosuppressive therapy; Liver transplant; Renal transplantation