Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up

Abstract

Rabbit anti-thymocyte globulin (rATG)-based immunosuppression induction is being increasingly used in liver transplantation (LT) in conjunction with steroid-free protocols to delay the initiation of calcineurin inhibitors. This study reports a single-center comparison of transplant outcomes and complications in 3 immunosuppression eras. Data were obtained retrospectively from a center research database, and the analysis included LT patients from 2001 to 2008. The immunosuppression consisted of rATG induction in 3 doses (6 mg/kg in all): (1) the first dose was administered perioperatively [the rabbit anti-thymocyte globulin in the operating room (rATG-OR) era]; (2) the first dose was delayed until 48 hours after transplantation [the rabbit anti-thymocyte globulin after a delay (rATG-D) era]; or (3) the first dose was delayed until 48 hours after transplantation, and a single dose of rituximab was added 72 hours after transplantation [the rabbit anti-thymocyte globulin after a delay plus rituximab (rATG-D-Ritux) era]. The initial maintenance immunosuppression was tacrolimus monotherapy, which was started on postoperative day 2. There were 166 patients (16%) in the rATG-OR era, 259 patients (26%) in the rATG-D era, and 588 patients (58%) in the rATG-D-Ritux era (1013 patients in all). Demographically, the latter eras were characterized by higher recipient and donor ages; greater percentages of liver-kidney transplants, hepatocellular carcinoma (HCC), donation after cardiac death (DCD), and imported organs; and shorter graft ischemia times. There were no significant differences between the 3 immunosuppression groups in unadjusted patient survival 3 and 5 years after transplantation (80% and 75% for the rATG-OR era, 75% and 67% for the rATG-D era, and 79% and 71% for the rATG-D-Ritux era, P ¼ 0.15). The 5-year survival rates for patients with hepatitis C virus (HCV) and HCC were 65% and 68%, respectively. The factors included in the Cox regression model for patient death included the Model for End-Stage Liver Disease score [hazard ratio (HR) ¼ 1.03, P ¼ 0.001], HCV (HR ¼ 1.28, P ¼ 0.04), donor age (HR ¼ 1.01, P ¼ 0.001), recipient age (HR ¼ 1.01, P ¼ 0.05), and DCD (HR ¼ 1.55, P ¼ 0.11). rATG-based induction immunosuppression can be safely used in adult LT recipients with excellent survival and low rejection rates and without increases in immunosuppression-related side effects. Liver Transpl 18: 786-795, 2012. V C 2012 AASLD. Received November 19, 2011 accepted January 7, 2012. Abbreviations: CI, confidence interval; CMV, cytomegalovirus; DCD, donation after cardiac death; DVT, deep venous thrombosis; GFR, glomerular filtration rate; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HR, hazard ratio; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; PTLD, posttransplant lymphoproliferative disorder; rATG, rabbit antithymocyte globulin; rATG-D, rabbit anti-thymocyte globulin after a delay; rATG-D-Ritux, rabbit anti-thymocyte globulin after a delay plus rituximab; rATG-OR, rabbit anti-thymoc...

Untitled

“…Mangus and associates retrospectively assessed their outcomes of using different regimens of rATG in 1000 orthotopic liver transplants and likewise found that the use of rATG-based induction immunosuppression can be safely used in adult orthotopic liver transplant recipients with excellent survival and low rejection rates. 24 Our study has several limitations. First are the limitations inherent to retrospective and single center studies.…”

Is Minimal, [Almost] Steroid-Free Immunosuppression a Safe Approach in Adult Liver Transplantation? Long-term Outcome of a Prospective, Double Blind, Placebo-Controlled, Randomized, Investigator-Driven Study

“…The results obtained in minimization IS trials should stimulate the transplant community to move from the "passive" industry driven to the more "active" investigator-driven studies. 43,[48][49][50] Such change in attitude will be the only way to progress further in the field of both IS and operational tolerance induction. 50…”

A Novel Approach in Combined Liver and Kidney Transplantation With Long-term Outcomes

“…Details of this approach have been reported previously. 17 Briefly, delayed closure of the abdomen aims to minimize the risk of abdominal compartment syndrome (and its stress on the native kidneys); prevent graft congestion in the critical postreperfusion period; re-assess for early duct necrosis and bile leak, unrecognized bowel injuries, and bowel obstructions; and wash-out the abdomen to evacuate any fluid collection or hematoma. In the case of delayed KT (group 2), the second-look operation was performed as usual, followed by KT through a separate incision.…”