title: Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantation.
abstract: BACKGROUND
  This is a 4-yr follow-up of a trial using mycophenolate mofetil (MMF) induction in orthotopic liver transplantation (OLT). The goal of this study was to evaluate a multidrug approach that would reduce both early and long-term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection.
  
  
  METHODS
  This was a prospective, randomized, intent to treat study designed to compare the primary endpoints of rejection and infection, and secondary endpoints of liver function, renal function, bone marrow function, cardiovascular risk factors, and the recurrence of hepatitis C. Ninety-nine consecutive patients with end stage liver disease who underwent OLT were randomized to receive either cyclosporine microemulsion (N) (50 patients) or tacrolimus (FK) (49 patients) starting on postoperative day 2, with MMF and an identical steroid taper begun preoperatively.
  
  
  RESULTS
  Ninety of 99 patients (N 46, FK 44) completed the 4-yr follow-up. The overall 4-yr patient and graft survivals were 93 and 89%, respectively. There was no significant difference in 4-yr patient (N 96% vs. FK 90%, p = ns) or graft (N, 90% vs. FK, 88%, p = ns) survival between groups. The 4-yr rejection rate was not significantly different in either arm (N = 34%, FK = 24%; p = 0.28). There were no differences in infection rates in either arm. The patients with hepatitis C had no differences in the viral titers or Knodell biopsy scores between groups. However, in the hepatitis C subgroup (37 patients), the FK patients had a significantly lower rejection rate (p = 0.0097) and a significantly lower clinically recurrent hepatitis C rate (p = 0.05) than the N patients. No difference was seen in the percent of patients weaned off of steroids after 4 yr (N 51%, FK 49%). There were no differences in the incidences of diabetes mellitus and hypertension. When renal dysfunction was analyzed, a significant difference in the number of patients whose creatinine had increased twofold since transplant was seen (N 63%, FK 38%, p = 0.04).
  
  
  CONCLUSIONS
  Use of MMF induction and maintenance following OLT in conjunction with either N or FK and an identical steroid taper, resulted in an acceptable long-term incidence of rejection and infection, without an increase in long-term graft or patient morbidity.
authors.affiliation: Department of Surgery, Division of Transplantation, Virginia Commonwealth University Health Systems at Medical College of Virginia Hospitals, Richmond, 23298-0254, USA. rafisher@hsc.vcu.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
authors.forename: James J
authors.initials: JJ
authors.lastname: Stone
authors.forename: Luke G
authors.initials: LG
authors.lastname: Wolfe
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Rodgers
authors.forename: Melodie L
authors.initials: ML
authors.lastname: Anderson
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Velimer A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Contos
authors.forename: A Scott
authors.initials: AS
authors.lastname: Mills
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferreira-Gonzalez
authors.forename: Marc P
authors.initials: MP
authors.lastname: Posner
mesh_terms: D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000601:surgery / Q000821:virology; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010359:Patient Readmission / Q000706:statistics & numerical data; D011446:Prospective Studies; D012074:Remission Induction; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus