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 > 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.
Kato
Tomoaki
T
Department of Surgery, University of Miami School of Medicine, Miami, FL, USA. tkato@med.miami.edu
Gaynor
Jeffrey J
JJ
Yoshida
Hideo
H
Montalvano
Marzia
M
Takahashi
Hidenori
H
Pyrsopoulos
Nikolaos
N
Nishida
Seigo
S
Moon
Jang
J
Selvaggi
Gennaro
G
Levi
David
D
Ruiz
Phillip
P
Schiff
Eugene
E
Tzakis
Andreas
A
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001706:Biopsy; D000077561:Daclizumab; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000628:therapy / Q000821:virology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012008:Recurrence; D013256:Steroids; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D013256:Steroids; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus