Reasons why some children receiving tacrolimus therapy require steroids more than 5 years post liver transplantation

Tacrolimus is a potent immunosuppressive agent and has been used in liver t ransplantation (LTx) for nearly a decade. More than 70% of children can be maintained on tacrolimus monotherapy, without steroids, by the end of 1 yr post-Tx. This freedom from steroids does not appear to change significantly in subsequent years. The use of steroids has obvious metabolic and cosmeti c disadvantages, besides affecting linear growth in children. The present s tudy identifies why some children still require steroid therapy after succe ssful LTx, One hundred and sixty-six consecutive pediatric patients who had undergone primary LTx between October 1989 and December 1992, were include d in this study. Follow-up ranged from 6 to 9 yr (mean 7.5 +/-0.8 yr). One hundred and forty-one children were alive in November 1998 and these patien ts constituted the study group. Their current rate of prednisone use, reaso n for prednisone use, and prednisone dose were examined retrospectively. Of the 141 patients, 139 (98.50%) had stopped taking steroids at some time-po int after LTx. Thirteen patients (9%) were off immunosuppression altogether (group I), 97 were undergoing tacrolimus monotherapy (group II), and the r emaining 31 were receiving therapy with steroids and tacrolimus (group III) . The mean prednisone dose at the last follow-up was 6.5 +/-4.9 mg/day (med ian 5.0 mg/day). In group III, two children were never weaned off steroids because of inadequate follow-up (both lived outside the country), and the r emaining 39 children completely stopped steroid therapy at some time-point after LTx; however, prednisone was re-introduced for clinically suspected o r. biopsy-proven rejection in 24. Seven children in group III had completel y stopped immunosuppressive therapy either as part of an immunosuppression reduction protocol (n=3) or for suspected or proven post-transplant lymphop roliferative disorder (PTLD) (n=4). In eleven of the 18 children in group I II, requirement of steroid for rejection was thought to be related, in part , to non-compliance. In three children in group III, steroids were re-intro duced for renal dysfunction, and two of these patients subsequently receive d a kidney Tx. In one child with cerebral ischemia, steroids were used to r educe brain edema, and another child had features of auto-immune hepatitis. Hence, almost all children can be weaned off steroids when tacrolimus is u sed as primary immunosuppression after primary LTx. However, approximate to 22% of children may need re-institution of steroids because of late acute rejection or renal dysfunction, The concomitant use of other non-steroidal immunosuppressive agents with tacrolimus may further reduce the dose and ra te of steroid use.