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

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 ?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 MNIF use appears to have significantly reduced the rejection rate.