0041-1337/99/6710-1308/0 TRANSPLANTATION Vol. 67, 1308 –1313, No. 10, May 27, 1999 Copyright © 1999 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. A PILOT STUDY ON THE SAFETY AND EFFECTIVENESS OF IMMUNOSUPPRESSION WITHOUT PREDNISONE AFTER LIVER TRANSPLANTATION GIUSEPPE TISONE, 1,2 MARIO ANGELICO, 3 GIANPIERO PALMIERI, 4 FRANCO PISANI, 1 ALESSANDRO ANSELMO, 1 LEONARDO BAIOCCHI, 3 STEFANO NEGRINI, 1 GIUSEPPE ORLANDO, 1 GIOVANNI VENNARECCI, 1 AND CARLO UMBERTO CASCIANI 1 Centro Trapianti d’Organo, Cattedre di Clinica Chirurgica, Gastroenterologia e Anatomia Patologica, Universita ` di Roma Tor Vergata, 00135 Rome, Italy Background. Corticosteroids are commonly used in the immunosuppression therapy after liver transplan- tation, yet are associated with considerable side ef- fects. Retrospective studies have shown that cortico- steroids can be safely withdrawn from months to years after transplant. We prospectively investigated the ef- fects of early immunosuppression without the use of corticosteroids on graft outcome and transplant com- plications. Methods. Forty-five patients undergoing liver trans- plantation were randomized to receive immunosup- pression 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 In those patients who received prednisone, this was withdrawn within 3 months after transplant.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 sur- vivors 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 complica- tions. 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 replica- tion HCV-RNA was faster among those treated with prednisone. The incidence and severity of acute rejec- tion 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 re- jection 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 in- sulin requirement than those treated without cortico- steroids. Conclusions. Liver transplantation can be per- formed safely without using corticosteroids in the early postoperative course, and there is no need for routine aggressive steroid treatment of established acute rejections. Standard regimens for immunosuppression therapy after liver transplantation always include the administration of corticosteroids, which are given continuously, for months to years, after surgery (1). The introduction of new potent im- munosuppressive drugs, such as tacrolimus or cyclosporine microemulsion (Neoral) has not changed this general ap- proach. However, the usefulness of corticosteroids after liver transplantation is far from certain. The rationale for their generalized use has been derived from experience in other organ transplantation settings, in which the occurrence of acute or chronic rejection is a matter of great clinical concern (2, 3). Liver transplant recipients, however, are much less prone to develop clinically significant acute or chronic rejec- tion (4) compared, for example, to kidney (5) and heart allo- graft recipients (6). On the other hand, it is well known that long-term steroidal administration, even at low doses, pre- disposes to a variety of metabolic complications (7) and, most importantly, to bacterial, fungal, and viral infections. Fur- thermore, in patients with hepatitis C virus (HCV*) infec- tion, high doses of intravenous corticosteroids commonly used to control acute rejections have been found to be asso- ciated with massive increase of viremia (8). There have been a number of attempts to withdraw corti- costeroids as early as possible after liver transplantation, both in adults (9) and in children (10). Retrospective studies have shown that prednisone withdrawal late after liver transplantation is associated with reduced incidence of dia- betes, arterial hypertension, and hypercholesterolemia with- out causing graft loss (9 –13). This indeed has induced several transplant centers to discontinue corticosteroids within 3–12 months after transplant. However, for how long steroidal administration may be useful after liver transplantation is still undetermined; furthermore, no prospective data exist to assess whether this treatment is safe and cost-effective in the early posttransplant course. To address the latter points, we conducted a prospective open-label randomized pilot study on a consecutive series of 1 Centro Trapianti d’Organo, Clinica Chirurgica-Ospedale S. Eu- genio, Universita ` di Roma Tor Vergata. 2 Address correspondence to: Giuseppe Tisone, M.D., Clinica Chirurgica, Ospedale S. Eugenio, Piazzale dell’Umanesimo 1, 00142 Rome, Italy. 3 Cattedra di Gastroenterologia Universita ` di Roma Tor Vergata. 4 Cattedra di Anatomia Patologica, Universita ` di Roma Tor Ver- gata. * Abbreviations: CMV, cytomegalovirus; HBsAg, hepatitis B sur- face antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; OLTx, orthotopic liver transplant; WBC, white blood cell. 1308