title: Canadian national retrospective chart review comparing the long term effect of cyclosporine vs. tacrolimus on clinical outcomes in patients with post-liver transplantation hepatitis C virus infection.
abstract: The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the "era effect" of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P < 0.001). The observed significant increase  in the odds of acute/hyperacute (OR 6.49, P = 0.001) and chronic rejection (OR 10.45, P < 0.001) in the cyclosporine to tacrolimus switch group, accompanied by an increase in the odds of HCV-related death (OR 2.30, P < 0.047) compared to tacrolimus merits further study. A significant increase (P < 0.044) in new-onset diabetes mellitus with tacrolimus (28.3%) compared to cyclosporine (18.7%) was also observed. Pre-transplant diabetes mellitus was associated with a significantly increased likelihood of graft fibrosis (HR 1.95, P = 0.003).
authors: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. eric.yoshida@vch.ca
authors: Eric M
authors: EM
authors: Yoshida
authors: Leslie B
authors: LB
authors: Lilly
authors: Paul J
authors: PJ
authors: Marotta
authors: Andrew L
authors: AL
authors: Mason
authors: Marc
authors: M
authors: Bilodeau
authors: Marc
authors: M
authors: Vaillancourt
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002170:Canada; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000821:virology; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000209:etiology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000821:virology; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D012367:RNA, Viral; D016572:Cyclosporine; D016559:Tacrolimus