Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: A report of the U.S. multicenter liver study group

Linda S. Sher, Carlos A. Cosenza, Jacques Michel, Leonard Makowka, Charles M. Miller, Myron E. Schwartz, Ronald Busuttil, Sue Mcdiarmid, James F. Burdick, Andrew S. Klein, Carlos Esquivel, Goran Klintmalm, Marlon Levy, John P. Roberts, John R. Lake, Munci Kalayoglu, Anthony M. D'Alessandro, Robert D. Gordon, Andrei C. Stieber, Byers W. ShawJ. Richard Thistlethwaite, Peter Whittington, Russell H. Wiesner, Michael Porayko, J. Steve Bynon, Devin E. Eckhoff, Richard B. Freeman, Richard J. Rohrer, W. David Lewis, J. Wallis Marsh, Marion Peters, John Powelson, A. Benedict Cosimi

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Abstract

Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty- four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of ≤10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus ≤90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Original languageEnglish (US)
Pages (from-to)258-263
Number of pages6
JournalTransplantation
Volume64
Issue number2
DOIs
StatePublished - Jul 27 1997

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Tacrolimus
Liver Transplantation
Multicenter Studies
Liver
Graft Survival
Bilirubin
Therapeutics
Allografts
Transplantation
Cyclosporine
Cause of Death
Sepsis

ASJC Scopus subject areas

  • Transplantation

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Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation : A report of the U.S. multicenter liver study group. / Sher, Linda S.; Cosenza, Carlos A.; Michel, Jacques; Makowka, Leonard; Miller, Charles M.; Schwartz, Myron E.; Busuttil, Ronald; Mcdiarmid, Sue; Burdick, James F.; Klein, Andrew S.; Esquivel, Carlos; Klintmalm, Goran; Levy, Marlon; Roberts, John P.; Lake, John R.; Kalayoglu, Munci; D'Alessandro, Anthony M.; Gordon, Robert D.; Stieber, Andrei C.; Shaw, Byers W.; Thistlethwaite, J. Richard; Whittington, Peter; Wiesner, Russell H.; Porayko, Michael; Bynon, J. Steve; Eckhoff, Devin E.; Freeman, Richard B.; Rohrer, Richard J.; Lewis, W. David; Marsh, J. Wallis; Peters, Marion; Powelson, John; Cosimi, A. Benedict.

In: Transplantation, Vol. 64, No. 2, 27.07.1997, p. 258-263.

Research output: Contribution to journalArticle

Sher, LS, Cosenza, CA, Michel, J, Makowka, L, Miller, CM, Schwartz, ME, Busuttil, R, Mcdiarmid, S, Burdick, JF, Klein, AS, Esquivel, C, Klintmalm, G, Levy, M, Roberts, JP, Lake, JR, Kalayoglu, M, D'Alessandro, AM, Gordon, RD, Stieber, AC, Shaw, BW, Thistlethwaite, JR, Whittington, P, Wiesner, RH, Porayko, M, Bynon, JS, Eckhoff, DE, Freeman, RB, Rohrer, RJ, Lewis, WD, Marsh, JW, Peters, M, Powelson, J & Cosimi, AB 1997, 'Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: A report of the U.S. multicenter liver study group', Transplantation, vol. 64, no. 2, pp. 258-263. https://doi.org/10.1097/00007890-199707270-00014
Sher, Linda S. ; Cosenza, Carlos A. ; Michel, Jacques ; Makowka, Leonard ; Miller, Charles M. ; Schwartz, Myron E. ; Busuttil, Ronald ; Mcdiarmid, Sue ; Burdick, James F. ; Klein, Andrew S. ; Esquivel, Carlos ; Klintmalm, Goran ; Levy, Marlon ; Roberts, John P. ; Lake, John R. ; Kalayoglu, Munci ; D'Alessandro, Anthony M. ; Gordon, Robert D. ; Stieber, Andrei C. ; Shaw, Byers W. ; Thistlethwaite, J. Richard ; Whittington, Peter ; Wiesner, Russell H. ; Porayko, Michael ; Bynon, J. Steve ; Eckhoff, Devin E. ; Freeman, Richard B. ; Rohrer, Richard J. ; Lewis, W. David ; Marsh, J. Wallis ; Peters, Marion ; Powelson, John ; Cosimi, A. Benedict. / Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation : A report of the U.S. multicenter liver study group. In: Transplantation. 1997 ; Vol. 64, No. 2. pp. 258-263.
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abstract = "Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty- four patients (70.3{\%}) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7{\%}) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9{\%} and 48.5{\%} at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4{\%} and 81.2{\%}, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of ≤10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus ≤90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9{\%} and 65.9{\%}, respectively, compared with 73.2{\%} and 87.7{\%} for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3{\%}) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.",
author = "Sher, {Linda S.} and Cosenza, {Carlos A.} and Jacques Michel and Leonard Makowka and Miller, {Charles M.} and Schwartz, {Myron E.} and Ronald Busuttil and Sue Mcdiarmid and Burdick, {James F.} and Klein, {Andrew S.} and Carlos Esquivel and Goran Klintmalm and Marlon Levy and Roberts, {John P.} and Lake, {John R.} and Munci Kalayoglu and D'Alessandro, {Anthony M.} and Gordon, {Robert D.} and Stieber, {Andrei C.} and Shaw, {Byers W.} and Thistlethwaite, {J. Richard} and Peter Whittington and Wiesner, {Russell H.} and Michael Porayko and Bynon, {J. Steve} and Eckhoff, {Devin E.} and Freeman, {Richard B.} and Rohrer, {Richard J.} and Lewis, {W. David} and Marsh, {J. Wallis} and Marion Peters and John Powelson and Cosimi, {A. Benedict}",
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TY - JOUR

T1 - Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation

T2 - A report of the U.S. multicenter liver study group

AU - Sher, Linda S.

AU - Cosenza, Carlos A.

AU - Michel, Jacques

AU - Makowka, Leonard

AU - Miller, Charles M.

AU - Schwartz, Myron E.

AU - Busuttil, Ronald

AU - Mcdiarmid, Sue

AU - Burdick, James F.

AU - Klein, Andrew S.

AU - Esquivel, Carlos

AU - Klintmalm, Goran

AU - Levy, Marlon

AU - Roberts, John P.

AU - Lake, John R.

AU - Kalayoglu, Munci

AU - D'Alessandro, Anthony M.

AU - Gordon, Robert D.

AU - Stieber, Andrei C.

AU - Shaw, Byers W.

AU - Thistlethwaite, J. Richard

AU - Whittington, Peter

AU - Wiesner, Russell H.

AU - Porayko, Michael

AU - Bynon, J. Steve

AU - Eckhoff, Devin E.

AU - Freeman, Richard B.

AU - Rohrer, Richard J.

AU - Lewis, W. David

AU - Marsh, J. Wallis

AU - Peters, Marion

AU - Powelson, John

AU - Cosimi, A. Benedict

PY - 1997/7/27

Y1 - 1997/7/27

N2 - Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty- four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of ≤10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus ≤90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

AB - Background. A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Methods. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Results. Sixty- four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of ≤10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin >10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus ≤90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted >90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Conclusions. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

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