Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

Acute humoral rejection (AHR) is uncommon after ABO-compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specif ic antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Liver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

High tacrolimus intra-patient variability is associated with graft rejection,and de novo donor-specific antibodies occurrence after liver transplantation

AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver