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Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection
Author(s) -
Fontana Robert J.,
Brown Robert S.,
MorenoZamora Ana,
Prieto Martin,
Joshi Shobha,
Londoño MariaCarlota,
Herzer Kerstin,
Chacko Kristina R.,
Stauber Rudolf E.,
Knop Viola,
Jafri SyedMohammed,
Castells Lluís,
Ferenci Peter,
Torti Carlo,
Durand Christine M.,
Loiacono Laura,
Lionetti Raffaella,
Bahirwani Ranjeeta,
Weiland Ola,
Mubarak Abdullah,
ElSharkawy Ahmed M.,
Stadler Bernhard,
Montalbano Marzia,
Berg Christoph,
Pellicelli Adriano M.,
Stenmark Stephan,
Vekeman Francis,
IonescuIttu Raluca,
Emond Bruno,
Reddy K. Rajender
Publication year - 2016
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.24416
Subject(s) - daclatasvir , simeprevir , medicine , sofosbuvir , liver transplantation , gastroenterology , hepatitis c virus , ribavirin , cirrhosis , hepatitis c , liver disease , transplantation , virology , virus
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 60 mg/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 14.3 × 6 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