TY - JOUR
T1 - Randomized trial of steroid-free induction versus corticosteroid maintenance among orthotopic liver transplant recipients with hepatitis C virus
T2 - Impact on hepatic fibrosis progression at one year
AU - Kato, Tomoaki
AU - Gaynor, Jeffrey J.
AU - Yoshida, Hideo
AU - Montalvano, Marzia
AU - Takahashi, Hidenori
AU - Pyrsopoulos, Nikolaos
AU - Nishida, Seigo
AU - Moon, Jang
AU - Selvaggi, Gennaro
AU - Levi, David
AU - Ruiz, Phillip
AU - Schiff, Eugene
AU - Tzakis, Andreas
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2007/10
Y1 - 2007/10
N2 - 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 MMF use appears to have significantly reduced the rejection rate.
AB - 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 MMF use appears to have significantly reduced the rejection rate.
KW - Daclizumab induction
KW - Hepatitis C virus
KW - Mycophenolate mofetil
KW - Orthotopic liver transplantation
KW - Steroid-free maintenance
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U2 - 10.1097/01.tp.0000282914.20578.7b
DO - 10.1097/01.tp.0000282914.20578.7b
M3 - Article
C2 - 17984834
AN - SCOPUS:38449112478
VL - 84
SP - 829
EP - 835
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 7
ER -