Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection

Fecha de publicación: 01/04/2016

Autores de IIS La Fe

Martín Prieto Castillo

Autor

Participantes ajenos a IIS La Fe

Fontana RJ
Brown RS Jr
Moreno-Zamora A
Joshi S
Londono MC
Herzer K
Chacko KR
Stauber RE
Knop V
Jafri SM
Castells L
Ferenci P
Torti C
Durand CM
Loiacono L
Lionetti R
Bahirwani R
Weiland O
Mubarak A
ElSharkawy AM
Stadler B
Montalbano M
Berg C
Pellicelli AM
Stenmark S
Vekeman F
Ionescu-Ittu R
Emond B
Reddy KR

Grupos

Hepatología experimental y Trasplante hepático

Investigador Principal

Laia Tolosa Pardo

Abstract

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 +/- 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 +/- 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3x6 log(10) IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n=77), DCV+SMV (n=18), and DCV+SMV+SOF (n=2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status. Liver Transplantation 22 446-458 2016 AASLD

Datos de la publicación

ISSN/ISSNe:: 1527-6465, 1527-6473
Tipo:: Article
Páginas:: 446-458
DOI:: 10.1002/lt.24416
Factor de Impacto:: 1,636 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Moreno-Zamora A:: Ramon and Cajal Hospital, Madrid, Spain
Prieto M:: Hospital Universitario y Politecnico La Fe and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, Valencia, Spain
Londono MC:: Department of Hepatology, Hospital Clinic Barcelona, Barcelona, Spain
Herzer K:: Department for General, Viszeral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Stauber RE:: Department of Internal Medicine, Karl-Franzens-University, Graz, Austria
Knop V:: Department of Internal Medicine, University Hospital-Goethe University, Frankfurt, Germany
Castells L:: Internal Medicine Department, Hospital Universitary Vall Hebron, University of Barcelona, Barcelona, Spain
Ferenci P:: Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
Torti C:: Unit of Infectious and Tropical Diseases, Magna Graecia University, Cantanzaro, Italy
Loiacono L:: Hospital San Giovanni Battista, Torino, Italy
Lionetti R:: Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy
Weiland O:: Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
ElSharkawy AM:: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Medical Centre, Birmingham, United Kingdom
Stadler B:: Klinikum Wels-Grieskirchen, Grieskirchen, Austria
Montalbano M:: Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy
Berg C:: Department of Internal Medicine, Hepatology, Gastroenterology, Infectious Diseases, University Hospital of Tubingen, Tubingen, Germany
Pellicelli AM:: Liver Unit, San Camillo Forlanini Hospital, Rome, Italy
Stenmark S:: Division of Infectious Diseases, Umea University, Umea, Sweden
Vekeman F:: Analysis Group, Inc, Montreal, Quebec, Canada
Ionescu-Ittu R:: Analysis Group, Inc, Montreal, Quebec, Canada
Emond B:: Analysis Group, Inc, Montreal, Quebec, Canada