Interferon-Free Regimens in the Liver-Transplant Setting

 

 Permissions and Reprints

Abstract

During 2014 and 2015, different interferon- (IFN-) free regimens will be approved for use in chronic hepatitis C (HCV). The liver-transplantation (LT) setting is the field of hepatology where these regimens will have the highest and fastest impact. Indeed, one study using direct-acting antivirals has already proven the concept that graft HCV infection can be prevented by treating patients awaiting LT. Safety and efficacy of several IFN-free regimens are currently being assessed in patients with hepatitis C recurrence after LT, with good preliminary results. Nevertheless, there are some issues that need to be addressed in the peri-LT setting and are reviewed in this article: (1) efficacy of IFN-free regimens in patients with advanced cirrhosis and portal hypertension, (2) pharmacokinetics of new antivirals in patients with several grades of hepatic or renal impairment, (3) impact of the selection of drug-resistant HCV strains in patients with decompensated cirrhosis or with severe hepatitis C recurrence after LT, and (4) drug–drug interactions.

• References

• 1 Lange CM, Zeuzem S. Perspectives and challenges of interferon-free therapy for chronic hepatitis C. J Hepatol 2013; 58 (3) 583-592
  CrossrefPubMedGoogle Scholar
• 2 Garcia-Retortillo M, Forns X, Feliu A , et al. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology 2002; 35 (3) 680-687
  CrossrefPubMedGoogle Scholar
• 3 Crespo G, Mariño Z, Navasa M, Forns X. Viral hepatitis in liver transplantation. Gastroenterology 2012; 142 (6) 1373-1383 , e1
  CrossrefPubMedGoogle Scholar
• 4 Londoño MC, Crespo G, Forns X. Pretransplant and posttransplant treatment of hepatitis C virus infection with protease inhibitors. Curr Opin Organ Transplant 2013; 18 (3) 271-278
  CrossrefPubMedGoogle Scholar
• 5 Forns X, García-Retortillo M, Serrano T , et al. Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J Hepatol 2003; 39 (3) 389-396
  CrossrefPubMedGoogle Scholar
• 6 Peng CY, Chien RN, Liaw YF. Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy. J Hepatol 2012; 57 (2) 442-450
  CrossrefPubMedGoogle Scholar
• 7 Kim WR, Terrault NA, Pedersen RA , et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology 2009; 137 (5) 1680-1686
  CrossrefPubMedGoogle Scholar
• 8 Iacobellis A, Siciliano M, Perri F , et al. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol 2007; 46 (2) 206-212
  CrossrefPubMedGoogle Scholar
• 9 Carrión JA, Martínez-Bauer E, Crespo G , 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 (4) 719-728
  CrossrefPubMedGoogle Scholar
• 10 Everson GT, Terrault NA, Lok AS , et al; Adult-to-Adult Living Donor Liver Transplantation Cohort Study. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology 2013; 57 (5) 1752-1762
  CrossrefPubMedGoogle Scholar
• 11 Everson GT, Trotter J, Forman L , et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 2005; 42 (2) 255-262
  CrossrefPubMedGoogle Scholar
• 12 Coto-Llerena M, Pérez-Del-Pulgar S, Crespo G , et al. Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation. Am J Transplant 2011; 11 (5) 1051-1057
  CrossrefPubMedGoogle Scholar
• 13 Poordad F, McCone Jr J, Bacon BR , et al; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364 (13) 1195-1206
  CrossrefPubMedGoogle Scholar
• 14 Jacobson IM, McHutchison JG, Dusheiko G , et al; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364 (25) 2405-2416
  CrossrefPubMedGoogle Scholar
• 15 Sherman KE, Flamm SL, Afdhal NH , et al; ILLUMINATE Study Team. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011; 365 (11) 1014-1024
  CrossrefPubMedGoogle Scholar
• 16 Bacon BR, Gordon SC, Lawitz E , et al; HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364 (13) 1207-1217
  CrossrefPubMedGoogle Scholar
• 17 Zeuzem S, Andreone P, Pol S , et al; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364 (25) 2417-2428
  CrossrefPubMedGoogle Scholar
• 18 Fontaine H, Hezode C, Dorival C , et al. SVR12 rates and safety of triple therapy including telaprevir or boceprevir in 221 cirrhotic non-responders treated in the French early access program (ANRS CO20-CUPIC). J Hepatol 2013; 58: S27
  PubMedGoogle Scholar
• 19 Hézode C, Fontaine H, Dorival C , et al; CUPIC Study Group. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) - NCT01514890. J Hepatol 2013; 59 (3) 434-441
  CrossrefPubMedGoogle Scholar
• 20 Rutter K, Ferlitsch A, Maieron A , et al. Safety of triple therapy with telaprevir or boceprevir in hepatitis C patients with advanced disease- predictive factors for sepsis. J Hepatol 2013; 58: S30
  PubMedGoogle Scholar
• 21 Verna EC, Terry N, Lukose T , et al. High early response rates with protease inhibitor triple therapy in a multicenter cohort of HCV-infected patients awaiting liver transplantation. Hepatology 2012; 56 (Suppl. 01) 218A
  PubMedGoogle Scholar
• 22 Jacobson IM, Yoshida EM, Sulkowski MS , et al. Treatment with sofosbuvir + ribavirin for 12 weeks achieves SVR12 of 78% in G2/3 interferon-ineligible, -intolerant, or - unwilling: results of the phase 3 positron trial. J Hepatol 2013; 58: S28
  PubMedGoogle Scholar
• 23 Lawitz E, Mangia A, Wyles D , et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368 (20) 1878-1887
  CrossrefPubMedGoogle Scholar
• 24 Jacobson IM, Gordon SC, Kowdley KV , et al; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368 (20) 1867-1877
  CrossrefPubMedGoogle Scholar
• 25 Zeuzem S, Dusheiko G, Salupere R , et al. Sofosbuvir and Ribavirin for 12 or 24 Weeks for Patients with HCV Genotype 2 or 3: the VALENCE trial. Hepatology 2013; 58 (Suppl. 01) 733A
  PubMedGoogle Scholar
• 26 Osinusi A, Meissner EG, Lee YJ , et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 2013; 310 (8) 804-811
  CrossrefPubMedGoogle Scholar
• 27 Lalazeri J, Nelson D, Hyland R , et al. Once-daily sofosbuvir plus ribavirin given for 12 or 24 weeks in treatment-naïve patients with HCV: the QUANTUM study. J Hepatol 2013; 58 (Suppl. 01) S346
  PubMedGoogle Scholar
• 28 Gane EJ, Stedman CA, Hyland RH , et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology 2013; ; [Epub ahead of print]
  PubMedGoogle Scholar
• 29 Kohli A, Sims Z, Marti M , et al. Combination oral, ribavirin free, antiviral therapy to optimize treatment outcomes for hepatitis C treatment naïve patients: interim results from the NIAID SYNERGY trial. Late breaking abstract (LB 8). Paper presented at: 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1–5, 2013; Washington, DC
  PubMedGoogle Scholar
• 30 Jacobson I, Ghalib R, Rodriguez-Torres M , et al. SVR results of a once-daily regimen of Simeprevir (TMC435) plus Sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment naïve and prior null responder patients: the COSMOS study. Late breaking abstract (LB 3). Paper presented at: 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1–5, 2013; Washington, DC
  PubMedGoogle Scholar
• 31 Lawitz E, Poordad FF, Pang PS , et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2013; ; [Epub ahead of print]
  PubMedGoogle Scholar
• 32 Everson G, Sims K, Thuluvath P , et al. Phase 2b study of the interferon-free and ribavirin-free combination of daclatasvir, asunaprevir and BMS-791325 for 12 weeks in treatment-naive patients with chronic HCV genotype 1 infection. Late breaking abstract (LB 1). Paper presented at: 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1–5, 2013; Washington, DC
  PubMedGoogle Scholar
• 33 Ruane P, Ain D, Riad J , et al. Sofosbuvir plus ribavirin in the treatment of chronic HCV genotype 4 infection in patients of Egyptian ancestry. Hepatology 2013; 58 (Suppl. 01) 736A
  CrossrefPubMedGoogle Scholar
• 34 Chayama K, Suzuki Y, Ikeda K , et al. All-oral combination of daclatasvir plus asunaprevir in interferon ineligible naive/intolerant and nonresponder Japanese patients chronically infected with HCV genotype 1b: results from a phase 3 trial. Hepatology 2013; 58 (Suppl. 01) 313a
  CrossrefPubMedGoogle Scholar
• 35 Zeuzem S, Soriano V, Asselah T , et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med 2013; 369 (7) 630-639
  CrossrefPubMedGoogle Scholar
• 36 Dufour J-F, Buti M, Soriano V , et al. Interferon-free treatment with faldaprevir, deleobuvir (bi 207127) and ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b. Hepatology 2013; 58 (Suppl. 01) 744A
  PubMedGoogle Scholar
• 37 ClinicalTrials.gov. A study to evaluate the safety and effect of aBT-450, ritonavir and ABT-267 (ABT-450/r/ABT-267) and ABT-333 coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults with compensated cirrhosis. Available at: http://www.clinicaltrials.gov/ct2/results?term=NCT01704755&Search=Search . Accessed February 18, 2014
  PubMedGoogle Scholar
• 38 Canini L, DebRoy S, Mariño Z , et al. Hepatitis C virus kinetic comparison between non-cirrhotic patients and patients awaiting liver transplantation treated with intravenous silibinin monotherapy. Hepatology 2013; 58 (Suppl. 01) 758A
  PubMedGoogle Scholar
• 39 Polyak SJ, Oberlies NH, Pécheur EI, Dahari H, Ferenci P, Pawlotsky JM. Silymarin for HCV infection. Antivir Ther 2013; 18 (2) 141-147
  CrossrefPubMedGoogle Scholar
• 40 ClinicalTrials.gov. Sofosbuvir/ledipasvir fixed-dose combination + ribavirin in subjects with chronic HCV with advanced liver disease or post-liver transplant. Available at: http://www.clinicaltrials.gov/ct2/results?term=NCT02010255&Search=Search . Accessed February 18, 2014
  PubMedGoogle Scholar
• 41 Guidance for industry pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072123.pdf . Accessed February 18, 2014
  PubMedGoogle Scholar
• 42 Sekar V, Simion A, Peeters M , et al. Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment. J Hepatol 2011; 54 (Suppl. 01) S193
  PubMedGoogle Scholar
• 43 Simion A, Mortier S, Peeters M , et al. Pharmacokinetics of simeprevir (TMC435) in volunteers with severe renal impairment. Paper presented at: 8th Hepatitis PK Workshop; June 26–27, 2013; Cambridge, MA
  PubMedGoogle Scholar
• 44 Soriano V, Gane EJ, Angus P , et al. Efficacy and safety of the interferon (IFN)-free combination of BI 201335 + BI 207127 ± ribavirin (RBV) in treatment-naïve patients with HCV genotype (GT) 1 infection and compensated liver cirrhosis: Results from the SOUND-C2 study. Hepatology 2012; 56 (Suppl. 04) 234A
  PubMedGoogle Scholar
• 45 Huang F, Moschetti V, Lang B , et al. Pharmacokinetics, safety, and tolerability of faldaprevir in patients with different levels of renal impairment. Hepatology 2013; 58 (Suppl. 01) 431A-432A
  PubMedGoogle Scholar
• 46 Eley T, He B, Li J , et al. Effect of hepatic impairment on the pharmacokinetics of asunaprevir (BMS-650032, ASV). Hepatology 2012; 56 (4) 1065A
  PubMedGoogle Scholar
• 47 Garimella T, He B, Luo W , et al. Asunaprevir pharmacokinetics and safety in subjects with impaired renal function. Hepatology 2013; 58 (Suppl. 01) 430A
  PubMedGoogle Scholar
• 48 Bifano M, Sevinsky H, Persson A , et al. Single-dose pharmacokinetics of daclatasvir (DCV; BMS-790052) in subjects with hepatic impairment compared with healthy subjects. Hepatology 2011; 54 (S1): 1004A
  PubMedGoogle Scholar
• 49 Lee C. Daclatasvir: potential role in hepatitis C. Drug Des Devel Ther 2013; 7: 1223-1233
  PubMedGoogle Scholar
• 50 ClinicalTrials.gov. Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment. Available at: http://www.clinicaltrials.gov/ct2/results?term=NCT01830205&Search=Search . Accessed February 4, 2014
  PubMedGoogle Scholar
• 51 Khatri A, Gaultier I, Menon R , et al. Pharmacokinetics and safety of co-administered ABT-450 plus ritonavir (ABT 450/r), ABT-267 and ABT-333 as a single dose in subjects with normal hepatic function and in subjects with mild, moderate and severe hepatic impairment. Hepatology 2012; 56 (Suppl. 04) 555A
  PubMedGoogle Scholar
• 52 Tseng A. Drug interactions with investigational hepatitis c protease inhibitors. Available at: http://www.hcvdruginfo.ca/downloads/Hepatitis%20C-int_new%20PIs.pdf . Accessed February 18, 2014
  PubMedGoogle Scholar
• 53 Mariño Z, van Bommel F, Forns X , et al. New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C. Gut 2014; 63 (2) 207-215
  PubMedGoogle Scholar
• 54 Lawitz E, Rodriguez-Torres M, Cornpropst M , et al. The effect of hepatic impairment on the pharmacokinetics and antiviral activity of PSI-7977 in hepatitis C infected subjects treated for seven days. J Hepatol 2012; 56 (Suppl. 02) S445-S446
  PubMedGoogle Scholar
• 55 Cornpropst M, Denning J, Clemons D , et al. The effect of renal impairment and end stage renal disease on the single-dose pharmacokinetics of PSI-7977. J Hepatol 2012; 56 (Suppl. 02) S433
  PubMedGoogle Scholar
• 56 German P, Mathias A, Yang J , et al. The pharmacokinetics of ledipasvir, an HCV specific NS5A inhibitor in HCV-uninfected subjects with moderate and severe hepatic impairment. Hepatology 2013; 58 (Suppl. 01) 432A
  PubMedGoogle Scholar
• 57 Curry MP, Forns X, Chung RT , et al. Pretransplant sofosbuvir and ribavirin to prevent recurrence of HCV infection after liver transplantation. Hepatology 2013; 58 (Suppl. 01) 314A
  PubMedGoogle Scholar
• 58 Mariño Z, Crespo G, D'Amato M , et al. Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period. J Hepatol 2013; 58 (3) 415-420
  CrossrefPubMedGoogle Scholar
• 59 Rowe IA, Armstrong MJ, Parker R , et al. Scavenger receptor B-I antagonist ITX5061 modulates early HCV kinetics in patients undergoing liver transplantation: results of a phase Ib clinical trial. Hepatology 2013; 58 (Suppl. 01) 239A
  PubMedGoogle Scholar
• 60 ClinicalTrials.gov. A pilot study to examine the role of nitazoxanide to prevent recurrence of hepatitis C after transplantation. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01074203?term=NCT01074203&rank=1 Accesssed February 8, 2014
  PubMedGoogle Scholar
• 61 Ferenci P, Scherzer TM, Kerschner H , et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008; 135 (5) 1561-1567
  CrossrefPubMedGoogle Scholar
• 62 Neumann UP, Biermer M, Eurich D, Neuhaus P, Berg T. Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy. J Hepatol 2010; 52 (6) 951-952
  CrossrefPubMedGoogle Scholar
• 63 Beinhardt S, Rasoul-Rockenschaub S, Scherzer TM, Ferenci P. Silibinin monotherapy prevents graft infection after orthotopic liver transplantation in a patient with chronic hepatitis C. J Hepatol 2011; 54 (3) 591-592 , author reply 592–593
  CrossrefPubMedGoogle Scholar
• 64 Esser-Nobis K, Romero-Brey I, Ganten TM , et al. Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B. Hepatology 2013; 57 (3) 953-963
  CrossrefPubMedGoogle Scholar
• 65 Adam R, McMaster P, O'Grady JG , et al; European Liver Transplant Association. Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry. Liver Transpl 2003; 9 (12) 1231-1243
  CrossrefPubMedGoogle Scholar
• 66 Belli LS, Burroughs AK, Burra P , et al. Liver transplantation for HCV cirrhosis: improved survival in recent years and increased severity of recurrent disease in female recipients: results of a long term retrospective study. Liver Transpl 2007; 13 (5) 733-740
  CrossrefPubMedGoogle Scholar
• 67 Berenguer M, Ferrell L, Watson J , et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol 2000; 32 (4) 673-684
  CrossrefPubMedGoogle Scholar
• 68 Yilmaz N, Shiffman ML, Stravitz RT , et al. A prospective evaluation of fibrosis progression in patients with recurrent hepatitis C virus following liver transplantation. Liver Transpl 2007; 13 (7) 975-983
  CrossrefPubMedGoogle Scholar
• 69 Walter T, Dumortier J, Guillaud O, Hervieu V, Scoazec JY, Boillot O. Factors influencing the progression of fibrosis in patients with recurrent hepatitis C after liver transplantation under antiviral therapy: a retrospective analysis of 939 liver biopsies in a single center. Liver Transpl 2007; 13 (2) 294-301
  CrossrefPubMedGoogle Scholar
• 70 Neumann UP, Berg T, Bahra M , et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 2004; 41 (5) 830-836
  CrossrefPubMedGoogle Scholar
• 71 Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002; 122 (4) 889-896
  CrossrefPubMedGoogle Scholar
• 72 Gane EJ. The natural history of recurrent hepatitis C and what influences this. Liver Transpl 2008; 14 (Suppl. 02) S36-S44
  CrossrefPubMedGoogle Scholar
• 73 Garcia-Retortillo M, Forns X. Prevention and treatment of hepatitis C virus recurrence after liver transplantation. J Hepatol 2004; 41 (1) 2-10
  CrossrefPubMedGoogle Scholar
• 74 Gane EJ, Naoumov NV, Qian KP , et al. A longitudinal analysis of hepatitis C virus replication following liver transplantation. Gastroenterology 1996; 110 (1) 167-177
  CrossrefPubMedGoogle Scholar
• 75 Sánchez-Fueyo A, Restrepo JC, Quintó L , et al. Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation 2002; 73 (1) 56-63
  CrossrefPubMedGoogle Scholar
• 76 Neumann UP, Berg T, Bahra M , et al. Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up. Transplantation 2004; 77 (2) 226-231
  CrossrefPubMedGoogle Scholar
• 77 Blasco A, Forns X, Carrión JA , et al. Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation. Hepatology 2006; 43 (3) 492-499
  CrossrefPubMedGoogle Scholar
• 78 Berenguer M, Palau A, Aguilera V, Rayón JM, Juan FS, Prieto M. Clinical benefits of antiviral therapy in patients with recurrent hepatitis C following liver transplantation. Am J Transplant 2008; 8 (3) 679-687
  CrossrefPubMedGoogle Scholar
• 79 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 Transplant 2006; 6 (7) 1586-1599
  CrossrefPubMedGoogle Scholar
• 80 Xirouchakis E, Triantos C, Manousou P , et al. Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies. J Viral Hepat 2008; 15 (10) 699-709
  CrossrefPubMedGoogle Scholar
• 81 Coilly A, Roche B, Samuel D. Current management and perspectives for HCV recurrence after liver transplantation. Liver Int 2013; 33 (Suppl. 01) 56-62
  CrossrefPubMedGoogle Scholar
• 82 Chalasani N, Manzarbeitia C, Ferenci P , et al; Pegasys Transplant Study Group. Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials. Hepatology 2005; 41 (2) 289-298
  CrossrefPubMedGoogle Scholar
• 83 Samuel D, Bizollon T, Feray C , et al. Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology 2003; 124 (3) 642-650
  CrossrefPubMedGoogle Scholar
• 84 Carrión JA, Navasa M, García-Retortillo M , et al. Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study. Gastroenterology 2007; 132 (5) 1746-1756
  CrossrefPubMedGoogle Scholar
• 85 Faisal N, Renner EL, Bilodeau M , et al. Protease inhibitor-based triple therapy is highly effective in liver transplant recipients with genotype 1 hepatitis C recurrence: A Canadian multicentre experience. Hepatology 2013; 58 (Suppl. 01) 238A
  PubMedGoogle Scholar
• 86 Coilly A, Dumortier J, Botta-Fridlund D. Sustained virological response after protease inhibitor based therapy for hepatitis C recurrence after liver transplantation: a multicentric European experience. Hepatology 2013; 58 (Suppl. 01) 316A
  PubMedGoogle Scholar
• 87 Coilly A, Roche B, Dumortier J , et al. Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: A multicenter experience. J Hepatol 2014; 60 (1) 78-86
  CrossrefPubMedGoogle Scholar
• 88 Brown KA, Fontana RJ, Russo MW , et al. Twice daily telaprevir in combination with Peginterferon alfa 2a/Ribavirin in genotype 1 HCV liver transplant recipients: interim week 16 safety and efficacy results of hte prospective multicentre REFRESH study. Hepatology 2013; 58 (Suppl. 01) 209A
  PubMedGoogle Scholar
• 89 Verna EC, Burton Jr JR, O' Leary JG , et al. A multicenter study of protease inhibitor-triple therapy in HCV-infected liver transplant recipients: report from the CRUSH-C group. J Hepatol 2013; 51 (Suppl. 01) S10
  PubMedGoogle Scholar
• 90 Stravitz R, Levitsky J, Dodge J , et al. Higher sustained virologic response (SVR-12) achievable in liver transplant (LT) recipients with hepatitis C (HCV) treated with protease inhibitor (PI) triple therapy (TT). Hepatology 2013; 58 (Suppl. 01) 429A
  CrossrefPubMedGoogle Scholar
• 91 Hulskotte E, Gupta S, Xuan F , et al. Pharmacokinetic interaction between the hepatitis C virus protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers. Hepatology 2012; 56 (5) 1622-1630
  CrossrefPubMedGoogle Scholar
• 92 Garg V, van Heeswijk R, Lee JE, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology 2011; 54 (1) 20-27
  CrossrefPubMedGoogle Scholar
• 93 Coilly A, Furlan V, Roche B , et al. Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence. Antimicrob Agents Chemother 2012; 56 (11) 5728-5734
  CrossrefPubMedGoogle Scholar
• 94 Mathias A, Cornpropst M, Clemons D , et al. No clinically significant pharmacokinetic drug-drug interactions between sofosbuvir (GS-7977) and the immunosuppressants, cyclosporine A or tacrolimus in healthy volunteers. Hepatology 2012; 56 (Suppl. 01) 1063A-1064A
  PubMedGoogle Scholar
• 95 Ouwerkerk-Mahadevan S, Simion A, Mortier S , et al. No clinically significant interaction between the investigational HCV protease inhibitor TMC435 and the immunosuppressives cyclosporine and tacrolimus. Hepatology 2012; 56 (Suppl. 01) 231A
  PubMedGoogle Scholar
• 96 Fontana RJ, Hughes EA, Appelman H, Hindes R, Dimitrova D, Bifano M. Case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis C after liver retransplantation. Liver Transpl 2012; 18 (9) 1053-1059
  CrossrefPubMedGoogle Scholar
• 97 Charlton M, Gane EJ, Manns M, Forns X. Sofosbuvir and ribavirin for the treatment of established recurrent hepatitis C infection after liver transplantation: preliminary results of a prospective, multicenter study. Late-breaking abstract (LB 2). Paper presented at: the 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1–5, 2013; Washington, DC
  PubMedGoogle Scholar
• 98 Forns X, Fontana RJ, Moonka D , et al. Initial evaluation of the sofosbuvir compassionate use program for patients with severe recurrent HCV following liver transplantation. Hepatology 2013; 58 (Suppl. 01) 732A
  PubMedGoogle Scholar
• 99 Fontana RJ, Hughes EA, Bifano M , et al. Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C. Am J Transplant 2013; 13 (6) 1601-1605
  CrossrefPubMedGoogle Scholar
• 100 Bárcena R, Moreno A, Rodríguez-Gandía MA , et al; Hospital Ramón y Cajal Liver Transplant Group. Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period. J Hepatol 2013; 58 (3) 421-426
  CrossrefPubMedGoogle Scholar
• 101 Eurich D, Bahra M, Berg T , et al. Treatment of hepatitis C-virus-reinfection after liver transplant with silibinin in nonresponders to pegylated interferon-based therapy. Exp Clin Transplant 2011; 9 (1) 1-6
  PubMedGoogle Scholar
• 102 ClinicalTrials.gov. A study to evaluate chronic hepatitis C infection in adult liver transplant recipients. Available at: http://www.clinicaltrials.gov/ct2/results?term=NCT01782495&Search=Search . Accessed February 18, 2014
  PubMedGoogle Scholar
• 103 ClinicalTrials.gov. A study of pharmacokinetics, efficacy, safety, tolerability, of the combination of simeprevir (TMC435), daclatasvir (BMS-790052), and ribavirin (RBV) in patients with recurrent chronic hepatitis C Genotype 1b infection after orthotopic liver transplantation. Available at: http://www.clinicaltrials.gov/ct2/results?term=NCT01938625&Search=Search . Accessed February 18, 2014
  PubMedGoogle Scholar
• 104 Sulkowski MS, Gardiner DF, Rodriguz-Torres M , et al. Daclatasvir plus Sofobovir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370: 211-212
  CrossrefPubMedGoogle Scholar