Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double-blinded trial.
BACKGROUND
The aim of this prospective, randomized, double-blinded, placebo-controlled single center study was to evaluate an early steroid-free immunosuppression in liver transplant patients.


METHODS
From March 2000 to October 2004, 110 patients were included. All patients received tacrolimus and steroids during the first 2 weeks after orthotopic liver transplantation (OLT). Thereafter, patients in the steroid group (n=54) received steroids and the remaining 56 a placebo. After 6 months, the immunosuppression for all was steroid free. Thirty patients were hepatitis C positive. Five years after inclusion, patient survival, organ survival, steroid side effects, and recirrhosis in hepatitis C virus (HCV) patients were reevaluated.


RESULTS
After 5 years, the following parameters were comparable in both groups: patient survival (P=0.236), organ survival (P=0.509), and acute rejections (P=0.409). Steroid-free immunosuppression lead to a higher rate of chronic rejections (P=0.023). Six months after OLT, there was a difference in rates of posttransplant diabetes mellitus (PTDM) (P=0.024) and hypercholesterolemia (P=0.002). However, 5 years after OLT, there was no difference in hypertension (P=0.647), PTDM (P=0.453), hypercholesterolemia (P=0.412), and osteoporosis (P=0.624). In HCV patients, we could not find any differences in patient survival (P=0.096), organ survival (P=0.424), time free from recirrhosis (P=0.647). The rate of recirrhosis was influenced by steroid bolus therapy (P=0.01) but not by avoiding continuous steroid therapy.


CONCLUSIONS
Early tapering down of steroids to a tacrolimus monotherapy is possible with comparable acute rejection rates. During steroid therapy, PTDM and hypercholesterolemia are cumulative. These side effects are reversible. The recirrhosis in HCV patients is not influenced by continuous steroid therapy but more frequent in HCV patients receiving a steroid bolus therapy.
Department of Transplantation and Hepatobiliarypancreatic Surgery, Hospital of Johannes Gutenberg University Mainz, Mainz, Germany. nina.weiler@unimedizin-mainz.de
Nina
N
Weiler
Ina
I
Thrun
Maria
M
Hoppe-Lotichius
Tim
T
Zimmermann
Irene
I
Kraemer
Gerd
G
Otto
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006085:Graft Survival / Q000187:drug effects; D006526:Hepatitis C / Q000601:surgery; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000601:surgery*; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D012008:Recurrence; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016559:Tacrolimus