title: 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 = 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) = 1.03, P = 0.001], HCV (HR = 1.28, P = 0.04), donor age (HR = 1.01, P = 0.001), recipient age (HR = 1.01, P = 0.05), and DCD (HR = 1.55, P = 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.
authors.affiliation: Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202-5250, USA. rmangus@iupui.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mangus
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fridell
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Vianna
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.forename: Jeanne
authors.initials: J
authors.lastname: Chen
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: Tector
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D000069283:Rituximab; D013256:Steroids / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D013256:Steroids; D000069283:Rituximab