Kelly D et al. (2004) Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial. Lancet 364: 1054–1061

Kelly et al. have performed the first randomized controlled trial of immunosuppression in pediatric liver transplant patients. This multicenter, open-label trial compared the efficacy of the two currently available calcineurin inhibitors—tacrolimus and ciclosporin microemulsion—in 181 children undergoing primary liver allograft transplantation at age 9–56 months.

At the time of transplantation, the children were randomly allocated to tacrolimus or ciclosporin microemulsion at the recommended initial daily doses of 0.30 mg/kg and 10 mg/kg, respectively. All patients received concomitant corticosteroids and the ciclosporin group also received azathioprine for at least the first 3 months.

At 12 months, the estimated acute rejection free rate was significantly higher in the tacrolimus group compared with the ciclosporin emulsion group (55.5% vs 40.2%, P = 0.0288), as was the estimated corticosteroid-resistant acute rejection rate (94.0% vs 70.4%, P < 0.0001). Estimated patient survival, graft survival and the incidence of adverse events were similar in both groups. In contrast to some previous reports, the authors note that there was no evidence for an increased risk of lymphoproliferative disease in children treated with tacrolimus.

In conclusion, the dual tacrolimus/steroids regimen was more effective than the triple ciclosporin microemulsion/steroids/azathioprine regimen in preventing biopsy-proven acute rejection in these patients. In addition, tacrolimus was associated with a better cardiovascular risk profile and so may offer long-term benefits.