Yoshida EM, Kwo P, Agarwal k, Duvoux C, Durand F, Peck-Radosavljevic M, Lilly L, Willems B, Vargas H, Kumar P, Brown RS, Horsmans JY, De-Oertel S, Arterburn S, Dvory-Sobol H, Brainard DM, McHutchison JG, Terrault N, Rizzetto M, Müllhaupt B

Language: English
References: 14
Page: 375-381
PDF size: 291.62 Kb.

ABSTRACT

Introduction. Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. Materials and methods. We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was ‹ 15 IU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for ‹ 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVR12) in patients with HCV RNA ‹ 15 IU/mL at their last measurement prior to transplant. Results. Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVR12 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA ‹ 15 IU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. Conclusion. Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.

REFERENCES

1. Taylor J, Cox-North P, Landis CS. Management of Post-Liver Transplant Recurrence of Hepatitis C. Drugs 2016; 76: 1711-7.

2. Berenguer M. Natural history of recurrent hepatitis C. Liver Transpl 2002; 8(Suppl. 1): S14-S18.

3. Pessoa MG, Bzowej N, Berenguer M, Phung Y, Kim M, Ferrell L, Hassoba H, et al. Evolution of hepatitis C virus quasispecies in patients with severe cholestatic hepatitis after liver transplantation. Hepatology 1999; 20: 1513-20.

4. Berenguer M, Prieto M, Palalu A, Rayon JM, Carrasco D, Juan FS, López-Labrador FX, et al. Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus-related graft cirrhosis. Liver Transpl 2003; 9: 228-35.

5. Wang CS, Ko HH, Yoshida EM, Marra CA, Richardson K. Interferon- based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transpl 2006; 6: 1586-99.

6. Carrion JA, Martinez-Bauer E, Crespo G, Ramirez S, Perezdel- Pulgar S, García-Valdecasas JC, Navasa M, et al. Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: a retrospective study. J Hepatol 2009; 50: 719-28.

7. Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS, Jr, Fried MW, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology 2015; 149: 649-59.

8. Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, Prieto M, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomized, phase 2 trial. Lancet Infect Dis 2016; 16: 685-97.

9. Curry MP, O’Leary JG, Bzowei N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015; 373: 2618-28.

10. Gutierrez JA, Carrion AF, Avalos D, O’Brien C, Martin P, Bhamidimarri KR, Peyton A, et al. Sofosbuvir and simeprevir for treatment of hepatitis C virus infection in liver transplant recipients. Liver Transpl 2015; 21: 823-30.

11. Faisal N, Bilodeau M, Aljudaibi B, Hirsch G, Yoshida EM, Hussaini T, Ghali MP, et al. Sofosbuvir-based antiviral therapy is highly effective in recurrent hepatitis C in liver transplant recipients: Canadian multicenter “real-life” experience. Transplantation 2016; 100: 1059-65.

12. Everson GT, Terrault NA, Lok AS, Rodrigo del R, Brown RS, Jr, Saab S, Shiffman ML, et al. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology 2013; 57: 1752-62.

13. Curry MP, Forns X, Chung RT, Terrault NA, Brown R Jr, Fenkel JM, Gordon F, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology 2015; 148: 100-07.

14. Belli LS, Bereguer M, Cortesi PA, Rockenschaub SR, Martini S, Morelli C, Donato F, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study. J Hepatol 2016; 65: 524-31.