A pilot study on the safety and effectiveness of immunosuppression without prednisone after liver transplantation.
BACKGROUND
Corticosteroids are commonly used in the immunosuppression therapy after liver transplantation, yet are associated with considerable side effects. Retrospective studies have shown that corticosteroids can be safely withdrawn from months to years after transplant. We prospectively investigated the effects of early immunosuppression without the use of corticosteroids on graft outcome and transplant complications.


METHODS
Forty-five patients undergoing liver transplantation were randomized to receive immunosuppression composed of cyclosporine microemulsion and azathioprine with (n=22) or without prednisone (n=23), in conventional doses. In those patients who received prednisone, this was withdrawn within 3 months after transplant. The median follow-up of survivors was 14 months (range: 6-24). The study end points were to determine graft survival and function, infectious complications, including hepatitis C virus (HCV)-RNA levels in HCV-infected recipients, acute rejection, kidney function, and metabolic complications.


RESULTS
Eleven deaths occurred, 6 of which were in the prednisone group. Two-year survival did not differ between patients treated with or without prednisone (70.2% vs. 78.3%, P=0.83), nor did the causes of death. No differences were observed with regard to graft function, renal function, and infectious complications. In the subset of patients who received transplants for HCV-related cirrhosis, the dynamics of virus replication HCV-RNA was faster among those treated with prednisone. The incidence and severity of acute rejection was similar in the two groups. More than 80% of acute rejections in both groups were classified as mild or moderate and underwent spontaneous resolution. Only two patients in each group had severe acute rejection requiring additional treatment with high-dose steroids. Patients receiving prednisone tended to have greater biochemical signs of cholestasis, higher serum cholesterol and glucose levels, and more frequent insulin requirement than those treated without corticosteroids.


CONCLUSIONS
Liver transplantation can be performed safely without using corticosteroids in the early postoperative course, and there is no need for routine aggressive steroid treatment of established acute rejections.
Tisone
G
G
Centro Trapianti d'Organo, Cattedre di Clinica Chirurgica, Gastroenterologia e Anatomia Patologica, Università di Roma Tor Vergata, Italy.
Angelico
M
M
Palmieri
G
G
Pisani
F
F
Anselmo
A
A
Baiocchi
L
L
Negrini
S
S
Orlando
G
G
Vennarecci
G
G
Casciani
C U
CU
D000328:Adult; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D013997:Time Factors
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D012367:RNA, Viral; D016572:Cyclosporine; D003404:Creatinine; D011241:Prednisone