title: Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.
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 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 log10 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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.affiliation: Ramon and Cajal Hospital, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno-Zamora
authors.affiliation: Hospital Universitario y Politécnico La Fe and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valencia, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Prieto
authors.affiliation: Department of Gastroenterology, Ochsner Health System, New Orleans, LA.
authors.forename: Shobha
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Hepatology, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Maria-Carlota
authors.initials: MC
authors.lastname: Londoño
authors.affiliation: Department for General, Viszeral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.affiliation: Einstein Center for Transplantation, Montefiore Medical Center, New York, NY.
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Chacko
authors.affiliation: Department of Internal Medicine, Karl-Franzens-University, Graz, Austria.
authors.forename: Rudolf E
authors.initials: RE
authors.lastname: Stauber
authors.affiliation: Department of Internal Medicine, University Hospital-Goethe University, Frankfurt, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Knop
authors.affiliation: Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI.
authors.forename: Syed-Mohammed
authors.initials: SM
authors.lastname: Jafri
authors.affiliation: Internal Medicine Department, Hospital Universitary Vall Hebron, University of Barcelona, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Castells
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Unit of Infectious and Tropical Diseases, Magna Graecia University, Cantanzaro, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.affiliation: Department of Medicine Infectious Diseases, Johns Hopkins Medical Institution, Baltimore, MD.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Durand
authors.affiliation: Hospital San Giovanni Battista, Torino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Loiacono
authors.affiliation: Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lionetti
authors.affiliation: Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: Ranjeeta
authors.initials: R
authors.lastname: Bahirwani
authors.affiliation: Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.affiliation: Department of Hepatology, Dallas Medical Physicians Group, Dallas, TX.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Mubarak
authors.affiliation: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Medical Centre, Birmingham, United Kingdom.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: ElSharkawy
authors.affiliation: Klinikum Wels-Grieskirchen, Grieskirchen, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Stadler
authors.affiliation: Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Montalbano
authors.affiliation: Department of Internal Medicine, Hepatology, Gastroenterology, Infectious Diseases, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Berg
authors.affiliation: Liver Unit, San Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: Pellicelli
authors.affiliation: Division of Infectious Diseases, Umea University, Umeå, Sweden.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stenmark
authors.affiliation: Analysis Group, Inc, Montreal, Quebec, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Vekeman
authors.affiliation: Analysis Group, Inc, Montreal, Quebec, Canada.
authors.forename: Raluca
authors.initials: R
authors.lastname: Ionescu-Ittu
authors.affiliation: Analysis Group, Inc, Montreal, Quebec, Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Emond
authors.affiliation: Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D057176:Compassionate Use Trials; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir