A Prospective Randomized Trial Comparing Interleukin-2 Receptor Antibody Versus Antithymocyte Globulin as Part of a Quadruple Immunosuppressive Induction Therapy Following Orthotopic Liver Transplantation

Langrehr, Jan M.; Nüssler, Natascha C.; Neumann, Ulf; Guckelberger, Olaf; Lohmann, R; Radtke, Arnold; Jonas, Sven; Klupp, J; Steinmüller, Th.; Lobeck, H.; Meuer, Stefan; H, Schlag; Lemmens, H. P.; Knoop, M.; Keck, H.; Bechstein, Wolf O.; Neuhaus, P.

doi:10.1097/00007890-199706270-00012

Cited by 55 publications

(28 citation statements)

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“…The expression of CD25 on T cells in the patients treated with ATG was found to be significantly lower than in non-ATG-treated patients at least 2 years postoperatively [6]. The IL-2/IL-2 receptor (IL-2R)-system plays an essential role in the antigenspecific clonal expansion of resting T cells within ongoing graft rejection [32, 351. Immunosuppressive agents directed against the IL-2R are of highly immunosuppressive potency [22,24,25,411. In contrast to other studies, a reduced incidence or severity of acute hepatic allograft rejection could not be found, despite the reduced CD25 expression, as well as the reduced percentage of T cells, especially of CD4+ T cells [13, 30, 33, 371. In addition, the expression of IL-2R (CD25) is necessary for the increased expression of the transferrin receptor (CD71), which is essential for the initiation of proliferation in nai've T cells.…”

Section: ~~~mentioning

confidence: 99%

“…In liver transplantation, several authors analyzed the effect of ATG on the incidence of acute rejection episodes, severe infectious complications, patient and graft survival, and secondary malignancies after transplantation. These studies showed the efficacy of polyclonal antibody induction therapy on both short-time and long-time clinical outcome of hepatic allografts [16,23,29,30,331. On the other hand, studies on cellular immune response focused on the early postoperative phase [23].…”

Section: Introductionmentioning

confidence: 98%

“…These studies showed the efficacy of polyclonal antibody induction therapy on both short-time and long-time clinical outcome of hepatic allografts [16,23,29,30,331. On the other hand, studies on cellular immune response focused on the early postoperative phase [23]. Today, it is well known that the addition of ATG failed significantly to improve clinical results after liver transplantation [25].…”

Section: Introductionmentioning

confidence: 98%

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Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

et al. 2002

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Various immunosuppressive regimens aim to reduce the incidence of acute rejection after liver transplantation. The efficacy of antithymocyte globulin (ATG) induction therapy and short-term effects on the cellular response have been demonstrated in several studies. Nevertheless, information about long-term effects of ATG therapy on cellular responses and frequency of complications is limited. Therefore, we analyzed the effect of ATG administration within a cyclosporine-based induction therapy, including azathioprine and prednisolone, on lymphocyte subsets and activation markers. We divided 35 liver transplant recipients into two groups according to their initial postoperative immunosuppression: a triple group without (n = 15) and a quadruple group with ATG (n = 20). The minimum observation time (flow cytometry analysis, clinical follow-up) was 2 years. Patients treated with ATG had persistently lower percentages of T cells for at least 2 years postoperatively ( P < 0.001). The CD4/CD8 ratios were lower in the quadruple group ( P < 0.005). The patients in the ATG group revealed a drop in CD25+ T cells within 2 years (P < 0.05).However, the percentage of CD7 1 + and HLA-DR+ T cells was temporarily higher in patients with ATG treatment ( P < 0.05). Patients with ATG treatment showed persistently higher levels of CD8+/CD57+ double positive cells in the late postoperative phase ( P < 0.05). In contrast, no differences could be observed between the two groups for major parameters of clinical outcome (acute rejections, severe infections, patient survival). We conclude that ATG therapy induces long-lasting alterations in T-cell subset composition. However, no beneficial clinical effect could be confirmed after liver transplantation.

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confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

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Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

et al. 2002

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“…[9][10][11][12] These triple or quadruple immunosuppressive protocols with ATG were proven to have low incidences of rejection with equivalent outcome. We recently reported the first pilot trial using RATG with tacrolimus and MMF and the total absence of steroids in OLT.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] RATG in conjunction with steroids has been shown to effectively reduce the incidence of rejection in OLT without an increased incidence of infectious complications or malignancy. 9,10,12 We previously reported a pilot trial showing the safety and efficacy of a 2-dose regimen of RATG without steroids in OLT. 13 The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with RATG in an effort to determine the need for steroids in OLT and prevent the adverse effects of steroids in liver transplant recipients.…”

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Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Eason

Loss

Blazek

et al. 2001

Liver Transplantation

121

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Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P ‫؍‬ .01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P ‫؍‬ not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT. (Liver Transpl 2001;7: 693-697.) S teroids have been a cornerstone of immunosuppression since the inception of transplantation and are credited with both the prevention and treatment of rejection. However, steroids have also been shown to increase infectious complications, bone disease, and posttransplantation diabetes and possibly increase the incidence and severity of recurrent hepatitis C virus (HCV) infecti...

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Antibody induction versus corticosteroid induction for liver transplant recipients

Penninga

Wettergren

Chan

et al. 2014

Cochrane Database of Systematic Reviews

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A Prospective Randomized Trial Comparing Interleukin-2 Receptor Antibody Versus Antithymocyte Globulin as Part of a Quadruple Immunosuppressive Induction Therapy Following Orthotopic Liver Transplantation

Cited by 55 publications

References 44 publications

Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Antibody induction versus corticosteroid induction for liver transplant recipients

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