title: Impact of tacrolimus versus cyclosporine in hepatitis C virus-infected liver transplant recipients on recurrent hepatitis: a prospective, randomized trial.
abstract: Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation, but HCV recurrence is nearly universal and may worsen patient / graft outcomes. The frequency and severity of HCV recurrence has apparently increased in recent years, raising concern about a possible role for newer immunosuppression regimens in this increase, including potentially tacrolimus. We randomized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation. A pathologist blinded to treatment reviewed serial liver biopsies. Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 (P = .19) and failure / death were .25 and .28, respectively (P = .789). Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels (months 1, 6, and 12), no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates. In conclusion, choice of calcineurin inhibitors does not impact severity of recurrent HCV.
authors.affiliation: Liver Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. martinpx@cshs.org
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Robert M
authors.initials: RM
authors.lastname: Goldstein
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Crippin
authors.forename: Goran B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: William E
authors.initials: WE
authors.lastname: Fitzsimmons
authors.forename: Carol
authors.initials: C
authors.lastname: Uleman
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D012367:RNA, Viral; D016572:Cyclosporine; D016559:Tacrolimus