Indications for tacrolimus anti-rejection therapy in liver allograft recipients

We reviewed our experience with conversion to Tacrolimus after 600 liver transplantations, performed from September 1988 to March 1995. Conversion to Tacrolimus as an anti-rejection therapy was implemented in 78 patients because of chronic ductopenic rejection (n = 9), early chronic rejection (n = 5), OKT3-resistant cellular rejection (n = 12), steroid-resistant cellular rejection (n = 30), late-onset cellular rejection (n = 10), cellular rejection in patients suffering from cyclosporin malabsorption (n = 5) and uncomplicated cellular rejection (n = 7). Control of rejection was achieved in 72 of 78 patients (92%); 6 patients (18%) were non-responsive. Patient and graft survival were 82% and 77%, respectively. Fourteen patients died almost exclusively from opportunistic infections. Out of the six patients who did not respond to Tacrolimus treatment, four underwent successful retransplantation and two died from infections associated with a poor graft function. Overall, graft loss with or without patient death occurred in 6 of 9 patients undergoing chronic rejection, in 3 of 12 patients with OKT3-resistant cellular rejection, in 6 of 30 patients suffering from steroid-resistant cellular rejection and in one patient each suffering from late-onset or uncomplicated cellular rejection. In severe steroid-resistant cellular rejection, successful Tacrolimus rescue therapy corresponded to a significantly lower preconversion total serum bilirubin when compared to failures (9.9 +/- 6.8 mg% vs. 22.2 +/- 7.3 mg%, P < 0.05). Conversion to Tacrolimus was a reliable treatment option in liver allograft rejection. However, failures occurred in the OKT3- and steroid-resistant cellular rejection groups, and only in a subgroup of patients suffering from chronic rejection was a permanent benefit observed. Implementation of a conversion early in the course of a rejection episode may result in a further improved outcome. Predictive parameters, e.g. the total serum bilirubin in steroid-resistant cellular rejection, are still needed to select those patients who would profit rather from a retransplantation.