Is minimal, [almost] steroid-free immunosuppression a safe approach in adult liver transplantation? Long-term outcome of a prospective, double blind, placebo-controlled, randomized, investigator-driven study.
OBJECTIVE
To investigate the safety of minimal immunosuppression (IS) in liver transplantation (LT).


BACKGROUND
The lack of long-term follow-up studies, including pathologic data, has led to a protean handling of IS in LT.


METHODS
Between February 2000 and September 2004, 156 adults were enrolled in a prospective, randomized, double-blind, placebo-controlled minimization trial comparing tacrolimus placebo (TAC-PLAC) and TAC short-term steroid (TAC-STER) IS. All patients had a minimum clinical, biochemical, and histological follow-up of 5 years.


RESULTS
Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1% and 82.1% (P=0.89) and 74.2% and 76.9% (P=0.90), respectively. Five-year biopsies were available in 112 (89.6%) of 125 survivors. Twelve patients refused a biopsy because of their excellent evolution; tissue material was insufficient in 1 patient; 11 had normal liver tests; and 2 patients had developed alcoholic and secondary biliary cirrhosis. Histology was normal in 44 (39.3%) patients; 35 (31.3%) had disease recurrence. The remaining biopsies showed nonspecific chronic hepatitis (14.3%), mild inflammatory infiltrates (10.7%), and steatosis (3.5%). All findings were equally distributed between both groups. In each group, 3 patients (4.8%) presented with acute cellular rejection after the first year and only 1 (0.9%) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis. Arterial hypertension, diabetes mellitus, renal insufficiency, hypercholesterolemia, gout, and obesity were equally low in both groups.


CONCLUSIONS
Excellent long-term results can be obtained under minimal IS and absence of steroids. TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up.
*Starzl Unit of Abdominal Transplantation †Department of Pathology ‡Department Immunology, and §Department of Experimental Surgery, University Hospitals Saint-Luc, Université catholique Louvain (UCL), Brussels, Belgium ¶Department of Liver Transplantation, University of Sao Paulo (USP), Sao Paulo, Brazil ‖Department of Surgery, Section of Transplantation, Wake Forest School of Medicine, Winston-Salem, NC **Hepatobiliary Unit, Imbanaco Medical center, Cali, Colombia.
Jan P
JP
Lerut
Rafael S
RS
Pinheiro
Quirino
Q
Lai
Valentine
V
Stouffs
Giuseppe
G
Orlando
Juan Manuel Rico
JM
Juri
Olga
O
Ciccarelli
Christine
C
Sempoux
Francine M
FM
Roggen
Chantal
C
De Reyck
Dominique
D
Latinne
Pierre
P
Gianello
D000328:Adult; D001706:Biopsy; D004311:Double-Blind Method; D005260:Female; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D010919:Placebos; D011446:Prospective Studies; D012008:Recurrence; D013256:Steroids / Q000008:administration & dosage*; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010919:Placebos; D013256:Steroids; D016559:Tacrolimus