Monday, June 18, 2012

A case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis c following liver retransplantation

A case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis c following liver retransplantation†

Robert J. Fontana1,‡,*, Eric A. Hughes2, Henry Appelman3, Robert Hindes4, Dessislava Dimitrova2, Marc Bifano2DOI: 10.1002/lt.23482

Keywords:
  • Direct acting antiviral;
  • Interferon;
  • NS5A complex inhibitor;
  • Immunosuppression;
  • cyclosporine

Abstract
Recurrent hepatitis C virus infection following liver transplantation can lead to accelerated allograft injury and fibrosis. The aim of this study is to report the first ever use of daclatasvir (BMS-790052), a potent orally administered NS5A replication complex inhibitor, in combination with peginterferon╬▒ and ribavirin in a liver transplant recipient. A 49 year old female developed severe recurrent HCV genotype 1b infection 4 months after transplant with severe cholestasis on biopsy and an HCV RNA of 10,000,000 IU/ml, alk phos of 1525 IU/ml, and total bilirubin of 8.4 mg/dl. Despite partial virological suppression with peginterferon╬▒ and ribavirin, progressive allograft failure ensued culminating in retransplantation at 9 months. At 3 months after the second transplant, daclatasvir 20 mg per day, peginterferona2a 180 ug/ week and ribavirin 800 mg/ day were prescribed for early recurrent cholestatic HCV. Serum HCV RNA became undetectable at week 3 of treatment and remained undetectable during 24 weeks of triple therapy as well as during post-treatment follow-up. Daclatasvir was well-tolerated and the trough drug levels were within the targeted range throughout treatment. The cyclosporine trough levels were also stable during and after therapy.

Conclusion: The lack of anticipated drug-drug interactions between daclatasvir and the calcineurin inhibitors coupled with its potent antiviral efficacy make this agent in combination with peginterferon and ribavirin an attractive antiviral regimen worthy of further study in liver transplant recipients with recurrent HCV. © 2012 American Association for the Study of Liver Diseases

http://onlinelibrary.wiley.com/doi/10.1002/lt.23482/abstract

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