Fibrosis progression in maintenance liver transplant patients with hepatitis C recurrence: A randomised study of everolimus vs. calcineurin inhibitors

Liver International

Volumn 34, Issue 10, 2014, Pages 1513-1521

  Villamil, Federico G ^a   Gadano, Adrian C ^b   Zingale, Fernanda ^c   Perez, Roberto ^b   Gil, Octavio ^d   Yantorno, Silvina ^e   Mastai, Ricardo ^f   Cairo, Fernando O ^a   Otero, Alcira B ^g   Dong, Gaohong ^h   Lopez, Patricia ^h  

^a HOSPITAL BRITÁNICO DE BUENOS AIRES   (Argentina)

^b HOSPITAL ITALIANO DE BUENOS AIRES   (Argentina)

^c Instituto Cardiovascular de Rosario   (Argentina)

^d Sanatorio Allende   (Argentina)

^e HOSPITAL UNIVERSITARIO FUNDACIÓN FAVALORO   (Argentina)

^f HOSPITAL ALEMÁN   (Argentina)

^g Novartis Pharmaceuticals Corporation   (Argentina)

^h NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Cyclosporine; HCV; Ishak Knodell; mTOR; Tacrolimus

Indexed keywords

CALCINEURIN INHIBITOR; CYCLOSPORIN; EVEROLIMUS; MYCOPHENOLATE MOFETIL; MYCOPHENOLIC ACID; RIBAVIRIN; STEROID; TACROLIMUS; IMMUNOSUPPRESSIVE AGENT; RAPAMYCIN;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DISEASE COURSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DYSLIPIDEMIA; ERECTILE DYSFUNCTION; ERYTHEMA; ESTIMATED GLOMERULAR FILTRATION RATE; FEMALE; HEPATITIS C; HUMAN; HUMAN TISSUE; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA; IMMUNOSUPPRESSIVE TREATMENT; INFLUENZA; KIDNEY FAILURE; KIDNEY FUNCTION; LEUKOPENIA; LIVER BIOPSY; LIVER FIBROSIS; LIVER TRANSPLANTATION; MALE; MOUTH ULCER; MULTICENTER STUDY; PHASE 2 CLINICAL TRIAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RECURRENT INFECTION; STOMATITIS; UPPER RESPIRATORY TRACT INFECTION; ANALOGS AND DERIVATIVES; ARGENTINA; CLINICAL TRIAL; GRAFT RECIPIENT; LIVER CIRRHOSIS; MIDDLE AGED; NONPARAMETRIC TEST; ORGAN DYSFUNCTION SCORE; PATHOPHYSIOLOGY; PROCEDURES; RECURRENT DISEASE;

ARGENTINA; CALCINEURIN INHIBITORS; EVEROLIMUS; FEMALE; HEPATITIS C; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; LIVER CIRRHOSIS; MALE; MIDDLE AGED; ORGAN DYSFUNCTION SCORES; RECURRENCE; SIROLIMUS; STATISTICS, NONPARAMETRIC; TRANSPLANT RECIPIENTS;

EID: 84908142463     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.12416     Document Type: Article

References (26)

1. Gane EJ, Portmann BC, Nauumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996; 334: 815-20.
2. Samonakis DN, Germani G, Burroughs AK. Immunosuppression and HCV recurrence after liver transplantation. J Hepatol 2012; 56: 973-83.
3. Chen G, Chen H, Wang C, et al. Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts. PLoS ONE 2012; 7: e33626.
4. Neef M, Ledermann M, Saegesser H, Schneider V, Reichen J. Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis. J Hepatol 2006; 45: 786-96.
5. Zhu J, Wu J, Frizell E, et al. Rapamycin inhibits stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis. Gastroenterology 1999; 117: 1198-204.
6. Patsenker E, Schneider V, Ledermann M, et al. Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol 2011; 55: 388-98.
7. Asthana S, Toso C, Meeberg G, et al. The impact of sirolimus on hepatitis C recurrence after liver transplantation. Can J Gastroenterol 2011; 25: 28-34.
8. McKenna GJ, Trotter JF, Klintmalm E, et al. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression. Am J Transpl 2011; 11: 2379-87.
9. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-9.
10. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431-5.
11. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24: 289-93.
12. Coresh J. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression. Am J Kidney Dis 2003; 41: 1-12.
13. Wagner D, Kniepeiss D, Schaffellner S, et al. Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates. Int Immunopharmacol 2010; 10: 990-3.
14. Samonakis DN, Cholongitas E, Triantos CK, et al. Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis. J Hepatol 2005; 43: 1091-3.
15. Özdemir BH, Özdemir AA, Erdal R, Özdemir FN, Haberal M. Rapamycin prevents interstitial fibrosis in renal allografts through decreasing angiogenesis and inflammation. Transplant Proc 2011; 43: 524-6.
16. Tulek B, Kiyan E, Toy H, et al. Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats. Clin Invest Med 2011; 34: E341.
17. Attur MG, Patel R, Thakker G, et al. Differential anti-inflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production. Inflamm Res 2000; 49: 20-6.
18. Schena FP, Pascoe MD, Alberu J, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009; 87: 233-42.
19. Holdaas H, Rostaing L, Serón D, et al. Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study. Transplantation 2011; 92: 410-8.
20. Guba M, Pratschke J, Hugo C, et al. Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial. Transplantation 2010; 90: 175-83.
21. Mjörnstedt L, Sørensen SS, von zur Mühlen B, et al. Improved renal function after early conversion from a calcineurin inhibitor to everolimus: a randomized trial in kidney transplantation. Am J Transplant 2012; 12: 2744-53.
22. Lebranchu Y, Thierry A, Toupance O, et al. Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study. Am J Transplant 2009; 9: 1115-23.
23. Nankivell BJ, Borrows RJ, Fung CL-S, et al. Calcineurin inhibitor nephrotoxicity: longitudinal assessment by protocol histology. Transplantation 2004; 78: 557-65.
24. De Simone P, Metselaar HJ, Fischer L, et al. Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: a prospective, randomized, multicenter trial. Liver Transpl 2009; 15: 1262-9.
25. Abdelmalek MF, Humar A, Stickel F, et al. Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial. Am J Transplant 2012; 12: 694-705.
26. Masetti M, Montalti R, Rompianesi G, et al. Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function. Am J Transplant 2010; 10: 2252-62.