Randomized trial of steroid-free induction versus corticosteroid maintenance among orthotopic liver transplant recipients with hepatitis C virus: impact on hepatic fibrosis progression at one year.

Author(s): Kato T, Gaynor JJ, Yoshida H, Montalvano M, Takahashi H, Pyrsopoulos N, Nishida S, Moon J, Selvaggi G, Levi D, Ruiz P, Schiff E, Tzakis A

Affiliation(s): Department of Surgery, University of Miami School of Medicine, Miami, FL, USA. tkato@med.miami.edu

Publication date & source: 2007-10-15, Transplantation., 84(7):829-35.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Due to the known high recurrence rate of hepatitis C virus (HCV) among orthotopic liver transplant (OLT) recipients who receive tacrolimus+corticosteroid maintenance, use of steroid-free induction was considered. METHODS: OLT recipients with HCV were randomized to receive tacrolimus+daclizumab (steroid-free) vs. tacrolimus+corticosteroids during 1999-2001 and then tacrolimus+mycophenolate mofetil (MMF)+daclizumab (steroid-free) vs. tacrolimus+MMF+corticosteroids during 2002-2005. Patients in the steroid-free arm of both periods received no steroids except for treating biopsy-proven rejection. Primary objective was to compare mean fibrosis stage at the 1-year protocol biopsy, between the steroid-free and corticosteroid arms, stratifying by period. RESULTS: No noticeable differences in mean fibrosis stage between the two treatment arms, either averaging across periods (P=0.99) or during either period (P>0.35) were found. Occurrence of acute rejection during the first year was the only factor associated with a significantly increased fibrosis stage at 1 year (P=0.0003); stage > or =2 was seen in 63% (17 of 27) vs. 19% (8 of 43) of those with vs. without rejection. In addition, MMF use was associated with significantly fewer patients experiencing acute rejection during the first 6 and 12 months posttransplant (P=0.006 and 0.046). Regarding steroid-related side effects, posttransplant diabetes mellitus occurred in 10% vs. 45%, and wound infection in 6% vs. 31% of steroid-free vs. corticosteroid patients (P=0.003 and 0.01). CONCLUSIONS: OLT recipients with HCV tolerated the steroid-free protocol with fewer side effects; however, its use had no apparent impact on hepatic fibrosis progression. Occurrence of acute rejection was strongly associated with increased hepatic fibrosis at 1 year, and MMF use appears to have significantly reduced the rejection rate.