Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report

Abstract

Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3-5 and maintaining parenteral whole-blood trough levels at 200-300 ng/ml during the first month and at 150-250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long-term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow-up after randomization was 6 months (6-27 months). Liver biochemistry was checked at regular intervals throughout the follow-up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long-term therapy. No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid-related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients and may be successfully accomplished in almost all patients.

Steroid sparing protocols following nonrenal transplants; the evidence is not there. A systematic review and meta-analysis

“…Incidence of AR was reported in 5 of 7 studies (412 patients) [9,13,25,29,33]. Two studies reported a statistically significant increase in the risk of AR [13,25].…”

“…Three studies reported information on serum liver function parameters (213 patients) [9,29,33]. No differences were observed between serum bilirubin, alkaline phosphatase (ALP) or aspartate transaminase (AST) in any study.…”

“…Four studies (582 patients) reported incidence of hypertension [16,20,25,29]. There was a nonsignificant reduction in hypertension with steroid withdrawal (random effects, RR 0.66, 95% CI: 0.40–1.08, P = 0.1; Fig.…”

“…This was the only study to report this outcome. Serum cholesterol levels were reported in four studies (472 patients) [16,20,29,33]. Meta‐analysis demonstrates a nonsignificant reduction in serum cholesterol with steroid withdrawal (random effects, −26.2 mg/dl, 95% CI: −58.4 to 6.03, P = 0.11; Fig.…”

Early cyclosporine monotherapy in liver transplantation: A 5-year follow-up of a prospective, randomized trial

“…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 10,11 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.…”