Sirolimus-based rescue therapy after rejection in liver transplantation

Abstract

Steroid-resistant acute rejection (SR-AR) and ductopenic rejection (DR) after liver transplantation are infrequent, but difficult to manage. We performed a retrospective review of patients with SR-AR or DR treated with sirolimus-based therapy. Since 2002, we have treated five patients with SR-AR and eight patients with DR. All patients had associated renal insufficiency. Six patients showed no response, of whom five died and one was retransplanted. In six cases, rejection was resolved after changing, while one improved. Therefore, the total response rate was 54%. Ten of 13 patients (77%) suffered some type of adverse event. Ten of these (77%) suffered a hematologic event. Four patients (31%) had infection. Only two patients had to discontinue treatment. Univariate analysis showed that pre-conversion bilirubin was lower in responders (Bilirubin: R: 210 +/- 205 vs. NoR: 554 +/- 159 micromol/L; p = 0.07 and Creatinine clearance higher: R: 37 +/- 11 vs. NoR: 25 +/- 11 mL/min; p = 0.09). Sirolimus trough levels one month after switching were higher in responders (R: 11 +/- 1.8 vs. NoR: 7.5 +/- 3.3 ng/mL; p = 0.03). We conclude that a dual therapy regimen of tacrolimus and sirolimus can achieve a high response rate as a rescue therapy for SR-AR and DR, provided it is begun as soon as possible.