title: A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for long-term liver allograft survival in recipients transplanted for hepatitis C.
abstract: Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a major barrier to survival of the transplanted liver. While cyclosporine (CsA) in vitro has been shown to suppress HCV replication, an effect is not seen with tacrolimus (Tac). Evidence is inconsistent whether or how this translates to clinical practice. To expand the evidence on this issue, we analyzed graft survival and histological outcomes after liver transplantation for HCV hepatitis.
  
  
  METHODS
  Using our longitudinal database (1991 onward) graft outcomes for all liver transplant recipients with HCV were evaluated (105 grafts in 97 patients). Severe activity, severe fibrosis, and graft survival were analyzed. All liver biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15, 14%). Comparisons of outcomes using CsA versus Tac therapy were done using survival analysis via the log-rank test.
  
  
  RESULTS
  Graft survival was significantly better in the CsA group. Although there was no apparent difference in severe activity (grade 2), there was a statistically significant difference in graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained response to antiviral therapy was twice as high in the CsA group, 50% versus 22% (P = 0.16; NS).
  
  
  CONCLUSIONS
  Graft survival in liver transplant recipients with HCV may be greater with CsA-based immunosuppression. There may also be a lower rate of fibrosing cholestatic hepatitis in this group.
authors.affiliation: Oregon Health Science University, USA. rayhills@ohsu.edu
authors.forename: S C
authors.initials: SC
authors.lastname: Rayhill
authors.forename: R
authors.initials: R
authors.lastname: Barbeito
authors.forename: D
authors.initials: D
authors.lastname: Katz
authors.forename: M
authors.initials: M
authors.lastname: Voigt
authors.forename: D
authors.initials: D
authors.lastname: Labrecque
authors.forename: P
authors.initials: P
authors.lastname: Kirby
authors.forename: R
authors.initials: R
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Stolpen
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
mesh_terms: D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use*; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D006526:Hepatitis C / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000276:immunology / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus