Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. We here report the final results of a prospective, randomized trial comparing early cyclosporine monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver transplantation patients. One hundred four patients were randomized 3 months after transplantation either to continue (Group I ؍ 50 patients) or to stop steroids (Group II ؍ 54 patients). Patients on a double-drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our main points of interest were the prevalence of acute and chronic rejections and steroidrelated side-effects in the two groups of patients. Mean follow-up was 41 ؎ 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%). The prevalence of acute rejections after randomization was, respectively, 8% and 4%. A single episode of chronic rejection was observed only in a patient on longterm steroid therapy. Side-effects of steroid therapy were less frequent in patients weaned off steroids, and when considering hypertension and diabetes, the differences between the two groups were statistically significant. Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid-related side-effects without increasing the risk of acute and chronic rejection. After 5 years, patient survival was similar in patients with or without steroids. (HEPATOL-OGY 1998;27:1524-1529.)
Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. Since the introduction of cyclosporine, corticosteroids have been shown to be a useful complement to the immunodepressive activity of cyclosporine and have been extensively used for induction and maintenance therapy in most transplantation centers. Nevertheless, the adverse effects of long-term corticosteroid therapy, particularly diabetes, hypercholesterolemia, bone diseases, arterial hypertension, and infections, have stimulated interest in the feasibility of steroid-free maintenance protocols. Corticosteroid withdrawal has been shown to be possible in almost 50% of kidney and heart recipients, and this observation has been confirmed in prospective studies. Surprisingly, despite the lower immunogenic potential of the grafted liver when compared with heart and kidney, long-term immunosuppression without steroids is not widely practiced in liver transplantation, and the true analysis of the risk-benefit ratio of this approach is difficult to ascertain because these studies are largely uncontrolled. A prospective, randomized trial of early cyclosporine monotherapy versus double-drug therapy (cyclosporine and corticosteroids) has been underway in our center since May 1991. Previous interim reports have suggested the feasibility of this protocol in the vast majority of our liver-transplant recipients. We are now able to report the final results on long-term follow-up (mean, 41 Ϯ 16 months) of 104 liver transplantation patients who were randomly allocated 3 months after transplantation either to continue (Group I) or to stop (Group II) corticosteroids. We were particularly interested in assessing the prevalence of acute and chronic rejections and of corticosteroid-induced side-effects in the two groups of patients.
Abbreviations: CC, cholangiocarcinoma; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus.