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

Robert J. Fontana, Robert S. Brown, Ana Moreno-Zamora, Martin Prieto, Shobha Joshi, Maria Carlota Londoño, Kerstin Herzer, Kristina R. Chacko, Rudolf E. Stauber, Viola Knop, Syed Mohammed Jafri, Lluís Castells, Peter Ferenci, Carlo Torti, Christine Durand, Laura Loiacono, Raffaella Lionetti, Ranjeeta Bahirwani, Ola Weiland, Abdullah Mubarak & 10 others Ahmed M. Elsharkawy, Bernhard Stadler, Marzia Montalbano, Christoph Berg, Adriano M. Pellicelli, Stephan Stenmark, Francis Vekeman, Raluca Ionescu-Ittu, Bruno Emond, K. Rajender Reddy

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)446-458
Number of pages13
JournalLiver Transplantation
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2016

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Hepatitis C
Hepacivirus
Liver
Infection
Liver Transplantation
Antiviral Agents
Ribavirin
Virus Diseases
Compassionate Use Trials
RNA
End Stage Liver Disease
BMS-790052
Simeprevir
Sofosbuvir
Transplant Recipients
Chronic Hepatitis C
Fibrosis
Therapeutics
Genotype
Research Personnel

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

Cite this

Fontana, R. J., Brown, R. S., Moreno-Zamora, A., Prieto, M., Joshi, S., Londoño, M. C., ... Reddy, K. R. (2016). Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. Liver Transplantation, 22(4), 446-458. https://doi.org/10.1002/lt.24416

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. / Fontana, Robert J.; Brown, Robert S.; Moreno-Zamora, Ana; Prieto, Martin; Joshi, Shobha; Londoño, Maria Carlota; Herzer, Kerstin; Chacko, Kristina R.; Stauber, Rudolf E.; Knop, Viola; Jafri, Syed Mohammed; Castells, Lluís; Ferenci, Peter; Torti, Carlo; Durand, Christine; 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; Ionescu-Ittu, Raluca; Emond, Bruno; Reddy, K. Rajender.

In: Liver Transplantation, Vol. 22, No. 4, 01.04.2016, p. 446-458.

Research output: Contribution to journalArticle

Fontana, RJ, Brown, RS, 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, C, 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 2016, 'Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection', Liver Transplantation, vol. 22, no. 4, pp. 446-458. https://doi.org/10.1002/lt.24416
Fontana, Robert J. ; Brown, Robert S. ; Moreno-Zamora, Ana ; Prieto, Martin ; Joshi, Shobha ; Londoño, Maria Carlota ; Herzer, Kerstin ; Chacko, Kristina R. ; Stauber, Rudolf E. ; Knop, Viola ; Jafri, Syed Mohammed ; Castells, Lluís ; Ferenci, Peter ; Torti, Carlo ; Durand, Christine ; 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 ; Ionescu-Ittu, Raluca ; Emond, Bruno ; Reddy, K. Rajender. / Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. In: Liver Transplantation. 2016 ; Vol. 22, No. 4. pp. 446-458.
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