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Yael Waknine
Medscape Medical News 2004. © 2004 Medscape

Basiliximab in a tacrolimus-based immunosuppressive regimen is effective in reducing incidences of acute cellular rejection (ACR) and improving ACR-free survival after orthotopic liver transplantation (OLTx), without increasing the incidence of adverse events or infections, according to the results of a prospective study published in the Sept. 27 issue of Transplantation, posted online Sept. 22.

"Induction with monoclonal antibodies for prevention of ACR may avoid many of the adverse events associated with polyclonal antibodies," writes Ignazio R. Marino, MD, FACS, director of the Division of Liver Transplantation and Hepatobiliary Surgery at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, and colleagues. "Basiliximab, a chimeric monoclonal antibody directed against the á-chain of the interleukin 2 receptor (CD25), has been extensively evaluated as an induction therapy for kidney transplant patients, more frequently in combination with a cyclosporine-based regimen."

To explore the efficacy and safety of basiliximab in combination with a cyclosporine-based regimen, the investigators analyzed 50 consecutive OLTx procedures (47 cadaveric donors, 3 living donors; mean age, 49.78 years; 35 men). Of these, 21 patients had hepatitis C virus (HCV)-related cirrhosis.

A 20-mg dose of basiliximab was administered to all patients at liver perfusion and on day 4 posttransplantation, followed by 0.15 mg/kg/day tacrolimus (target trough level, 10-15 ng/mL) and a tapered regimen of methylprednisolone.

The actuarial patient survival rate at three years was 88%, with a 75% rate of graft survival. Graft loss occurred in nine patients (18%), resulting in retransplantation. Four deaths occurred due to late graft failure. Two deaths resulted from sepsis that occurred in 12 patients (24%).

During the follow-up period (799.89 ± 257.37 days), 44 patients (88%) had no ACR episodes, five patients (10%) had one episode, and one patient (2%) had three episodes. Mean ACR rate was 0.15 ± 0.21 episodes per month. Rejection-free probability was 75% within the first three months.

According to the authors, the 12% three-year ACR rate compares favorably with the 38% one-year rejection rate recently reported in a French study, as well as the 45.2% one-year rejection rate reported in a study based at the University of Pittsburgh. "The difference is even more dramatic when our results are compared to the U.S. and European multicenter FK506 liver study groups, in which the 1-year rejection rates with steroids and tacrolimus were 68% and 40.5%, respectively," they point out.

Among the HCV-positive patients, nine (42%) developed HCV recurrence within the three-year follow-up period. According to the authors, this result compares favorably with the results of the University of Pittsburgh trial (42% - 53%). "[T]he addition of basiliximab to baseline immunosuppression in our study did not increase the HCV recurrence rate," the authors note. "This is particularly relevant because patients with recurrent HCV hepatitis show a higher incidence of late-occurring infections, mostly as a result of pathogens associated with depressed cell-mediated immunity."

Basiliximab was well-tolerated and no infusion adverse effects were observed. No cytomegalovirus infections or posttransplant lymphoproliferative disorders occurred.

"This study demonstrated that basiliximab...was effective in reducing the number of ACR episodes and increasing the probability of remaining rejection-free after OLTx, which could potentially result in improved long-term outcomes," the authors write, adding that basiliximab was safe and did not increase the adverse events profile or rate of infection.

"Investigation of the potential of this regimen for allowing later weaning from maintenance immunosuppressants is needed," the authors suggest. "Based on the favorable outcome observed in our patient population reported here, we believe that it would be appropriate to test a steroid-free immunosuppressive regimen based on tacrolimus and basiliximab in adult liver recipients...with particular attention to HCV recurrence in this subgroup of patients."