Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: Results of a prospective, randomized trial

Background. Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation. However, it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation. Therefore, we designed a prospective, randomized study to compare the immunosuppressive efficacy of dual (tacrolimus and prednisolone) and quadruple (tacrolimus, azathioprine, ALG Merieux and prednisolone) induction after liver transplantation. Methods, After randomization, 120 consecutive patients of primary liver transplants were divided into the dual group (n=59) and the quadruple group (n=61) and followed for a minimum of 3 years. Results. Patient survival at 3 years was 88.2% in the dual versus 94.9% in the quadruple group. Overall 25 patients in each group (41 and 42%, respectively) developed acute rejection. There was no difference in the number and severity of rejections. In each group only four patients required OKT3-therapy, however, although three of four patients in the quadruple group responded to OKT3 and cleared rejection, none of the four patients in the dual group were treated successfully with OKT3 (P<0.02), Rejection in these patients resolved only after additional treatment with mycophenolate mofetil, Adverse events and infections were equally distributed in both groups, Asymptomatic Cytomegalovirus infections were more common in the quadruple group (P<0.02). As of today, only one patient developed posttransplant lymphoproliferative disease (dual group). Conclusions. The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation.