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

Richard Mangus, Jonathan A. Fridell, Rodrigo M. Vianna, Paul Y. Kwo, Jeanne Chen, A. Joseph Tector

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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.

Original languageEnglish
Pages (from-to)786-795
Number of pages10
JournalLiver Transplantation
Volume18
Issue number7
DOIs
StatePublished - Jul 2012

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Antilymphocyte Serum
Immunosuppression
Rabbits
Transplants
Liver
Transplantation
Liver Transplantation
Hepacivirus
Rituximab
Hepatocellular Carcinoma
Tissue Donors
End Stage Liver Disease
Survival
Tacrolimus
Operating Rooms
Proportional Hazards Models
Ischemia
Survival Rate
Steroids
Maintenance

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

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Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up. / Mangus, Richard; Fridell, Jonathan A.; Vianna, Rodrigo M.; Kwo, Paul Y.; Chen, Jeanne; Tector, A. Joseph.

In: Liver Transplantation, Vol. 18, No. 7, 07.2012, p. 786-795.

Research output: Contribution to journalArticle

Mangus, Richard ; Fridell, Jonathan A. ; Vianna, Rodrigo M. ; Kwo, Paul Y. ; Chen, Jeanne ; Tector, A. Joseph. / Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up. In: Liver Transplantation. 2012 ; Vol. 18, No. 7. pp. 786-795.
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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.",
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