Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Steroids have been I of the primary modes of immunosuppression since the in ception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for in creased infections, posttransplantation diabetes, and recurrent hepatitis a fter orthotopic liver transplantation (OLT). The purpose of this ongoing pr ospective randomized trial is to eliminate steroid use in OLT through induc tion with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroi ds. Seventy-one adult patients were prospectively randomized to administrat ion of RATG or steroids. Thirty-six patients were randomized to the adminis tration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginni ng during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five p atients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were admin istered methylprednisolone, 1,000 mg IV, initiated during the anhepatic pha se and followed by steroid taper. Maintenance immunosuppression consisted o f tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (2 0.5%), all of whom were successful; treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patient s (36%) were successfully treated by increasing tacrolimus doses. The incid ence of rejection was not statistically significant; however, there was a s ignificant difference in the incidence of steroid-requiring rejection (P=.0 1). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P=not significant). The incidence and severity of inf ections complications were slightly lower in RATG patients, accounted for b y a greater incidence of cytomegalovirus (CMV) infection in the steroid pat ients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT dia betes and recurrent hepatitis C, and decreased CMW infection. This prospect ive randomized trial gives encouraging support that steroids can be safely eliminated in OLT.