Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection
Fontana RJ, Brown RS Jr, Moreno-Zamora A, Prieto M, Joshi S, Londoño 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. Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. Liver Transpl. 2016 Apr;22(4):446-58.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
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/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.
Medical Subject Headings
Aged; Antiviral Agents; Compassionate Use Trials; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Recurrence; Retrospective Studies; Ribavirin; Simeprevir; Sofosbuvir; Treatment Outcome