12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus

Gary Levy, Gian Luca Grazi, Fernando Sanjuan, Youmin Wu, Ferdinand Mühlbacher, Didier Samuel, Styrbjorn Friman, Robert Jones, Guido Cantisani, Frederico Villamil, Umberto Cillo, Pierre Alain Clavien, Goran Klintmalm, Gerd Otto, Stephen Pollard, P. Aiden McCormick, V. Descalsi, A. Gadano, A. Villamil, P. AngusS. Lynch, G. A. Balderson, G. Jeffreys, B. Chester, R. Steininger, B. de Hemptinne, R. Troisi, M. L. Zanotelli, L. Leonardi, I. Boin, S. Mies, B. D. Guardia, L. Lilly, P. Marotta, W. Wall, K. Peltekian, A. Roy, D. Marleau, C. Scudamore, M. Yoshida, J. Tchervenkov, M. Cantarovich, O. Boillot, P. Bernard, Y. Calmus, F. Conti, D. Cherqui, C. Duvoux, C. Ducerf, R. Maar, J. Gugenheim, A. Myx, D. Neau-Cransac, K. Mouette, F. Saliba, L. Rostaing, N. Kamar, C. Moench, M. O'Rourke, D. D'Amico, G. Varotti, A. Maffei-Faccioli, G. Gerunda, R. Merenda, A. Risaliti, U. Baccarani, M. Rossi, P. Berloco, K. Tanaka, F. Oike, S. Munn, E. Gane, I. Brekke, K. M. Boberg, A. Bernardos, I. Garcia, V. Cuervas, J. M. Moreno, A. Rimola, I. Cirera, F. Sanjuan, M. Prieto, M. Salcedo, G. Clemente, B. Ericson, H. Gjertsen, G. Herlenius, Z. Kadry, D. Mayer, P. Hayes, J. Davidson, J. Hodgson, J. S. Bynon, G. Davis, J. Ortiz, C. Manzarbeita, R. Mennon, R. H. Weisner, Y. Wu, R. Y. Chensu, J. R. Lake, A. Humar

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neural) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level[predose])Co to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% o tacrolimus patients survived with a functioning grat (P not significant). Efficacy was similar in deceased-and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME 95/ 88,6%) than with tacrolimus (14/85,16%) (P< 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months was (13% vs. 5%, P< 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70% vs. 49%, P+ 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Original languageEnglish (US)
Pages (from-to)1464-1472
Number of pages9
JournalLiver Transplantation
Volume12
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Tacrolimus
Liver Transplantation
Cyclosporine
Transplants
Hypoglycemic Agents
Hepacivirus
Liver
Recurrence
Drug Monitoring
Living Donors
Azathioprine
Therapeutics
Hepatitis C
Hyperlipidemias
Multicenter Studies
Creatinine
Steroids
Hypertension
Kidney
Biopsy

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus. / Levy, Gary; Grazi, Gian Luca; Sanjuan, Fernando; Wu, Youmin; Mühlbacher, Ferdinand; Samuel, Didier; Friman, Styrbjorn; Jones, Robert; Cantisani, Guido; Villamil, Frederico; Cillo, Umberto; Clavien, Pierre Alain; Klintmalm, Goran; Otto, Gerd; Pollard, Stephen; McCormick, P. Aiden; Descalsi, V.; Gadano, A.; Villamil, A.; Angus, P.; Lynch, S.; Balderson, G. A.; Jeffreys, G.; Chester, B.; Steininger, R.; de Hemptinne, B.; Troisi, R.; Zanotelli, M. L.; Leonardi, L.; Boin, I.; Mies, S.; Guardia, B. D.; Lilly, L.; Marotta, P.; Wall, W.; Peltekian, K.; Roy, A.; Marleau, D.; Scudamore, C.; Yoshida, M.; Tchervenkov, J.; Cantarovich, M.; Boillot, O.; Bernard, P.; Calmus, Y.; Conti, F.; Cherqui, D.; Duvoux, C.; Ducerf, C.; Maar, R.; Gugenheim, J.; Myx, A.; Neau-Cransac, D.; Mouette, K.; Saliba, F.; Rostaing, L.; Kamar, N.; Moench, C.; O'Rourke, M.; D'Amico, D.; Varotti, G.; Maffei-Faccioli, A.; Gerunda, G.; Merenda, R.; Risaliti, A.; Baccarani, U.; Rossi, M.; Berloco, P.; Tanaka, K.; Oike, F.; Munn, S.; Gane, E.; Brekke, I.; Boberg, K. M.; Bernardos, A.; Garcia, I.; Cuervas, V.; Moreno, J. M.; Rimola, A.; Cirera, I.; Sanjuan, F.; Prieto, M.; Salcedo, M.; Clemente, G.; Ericson, B.; Gjertsen, H.; Herlenius, G.; Kadry, Z.; Mayer, D.; Hayes, P.; Davidson, J.; Hodgson, J.; Bynon, J. S.; Davis, G.; Ortiz, J.; Manzarbeita, C.; Mennon, R.; Weisner, R. H.; Wu, Y.; Chensu, R. Y.; Lake, J. R.; Humar, A.

In: Liver Transplantation, Vol. 12, No. 10, 10.2006, p. 1464-1472.

Research output: Contribution to journalArticle

Levy, G, Grazi, GL, Sanjuan, F, Wu, Y, Mühlbacher, F, Samuel, D, Friman, S, Jones, R, Cantisani, G, Villamil, F, Cillo, U, Clavien, PA, Klintmalm, G, Otto, G, Pollard, S, McCormick, PA, Descalsi, V, Gadano, A, Villamil, A, Angus, P, Lynch, S, Balderson, GA, Jeffreys, G, Chester, B, Steininger, R, de Hemptinne, B, Troisi, R, Zanotelli, ML, Leonardi, L, Boin, I, Mies, S, Guardia, BD, Lilly, L, Marotta, P, Wall, W, Peltekian, K, Roy, A, Marleau, D, Scudamore, C, Yoshida, M, Tchervenkov, J, Cantarovich, M, Boillot, O, Bernard, P, Calmus, Y, Conti, F, Cherqui, D, Duvoux, C, Ducerf, C, Maar, R, Gugenheim, J, Myx, A, Neau-Cransac, D, Mouette, K, Saliba, F, Rostaing, L, Kamar, N, Moench, C, O'Rourke, M, D'Amico, D, Varotti, G, Maffei-Faccioli, A, Gerunda, G, Merenda, R, Risaliti, A, Baccarani, U, Rossi, M, Berloco, P, Tanaka, K, Oike, F, Munn, S, Gane, E, Brekke, I, Boberg, KM, Bernardos, A, Garcia, I, Cuervas, V, Moreno, JM, Rimola, A, Cirera, I, Sanjuan, F, Prieto, M, Salcedo, M, Clemente, G, Ericson, B, Gjertsen, H, Herlenius, G, Kadry, Z, Mayer, D, Hayes, P, Davidson, J, Hodgson, J, Bynon, JS, Davis, G, Ortiz, J, Manzarbeita, C, Mennon, R, Weisner, RH, Wu, Y, Chensu, RY, Lake, JR & Humar, A 2006, '12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus', Liver Transplantation, vol. 12, no. 10, pp. 1464-1472. https://doi.org/10.1002/lt.20802
Levy, Gary ; Grazi, Gian Luca ; Sanjuan, Fernando ; Wu, Youmin ; Mühlbacher, Ferdinand ; Samuel, Didier ; Friman, Styrbjorn ; Jones, Robert ; Cantisani, Guido ; Villamil, Frederico ; Cillo, Umberto ; Clavien, Pierre Alain ; Klintmalm, Goran ; Otto, Gerd ; Pollard, Stephen ; McCormick, P. Aiden ; Descalsi, V. ; Gadano, A. ; Villamil, A. ; Angus, P. ; Lynch, S. ; Balderson, G. A. ; Jeffreys, G. ; Chester, B. ; Steininger, R. ; de Hemptinne, B. ; Troisi, R. ; Zanotelli, M. L. ; Leonardi, L. ; Boin, I. ; Mies, S. ; Guardia, B. D. ; Lilly, L. ; Marotta, P. ; Wall, W. ; Peltekian, K. ; Roy, A. ; Marleau, D. ; Scudamore, C. ; Yoshida, M. ; Tchervenkov, J. ; Cantarovich, M. ; Boillot, O. ; Bernard, P. ; Calmus, Y. ; Conti, F. ; Cherqui, D. ; Duvoux, C. ; Ducerf, C. ; Maar, R. ; Gugenheim, J. ; Myx, A. ; Neau-Cransac, D. ; Mouette, K. ; Saliba, F. ; Rostaing, L. ; Kamar, N. ; Moench, C. ; O'Rourke, M. ; D'Amico, D. ; Varotti, G. ; Maffei-Faccioli, A. ; Gerunda, G. ; Merenda, R. ; Risaliti, A. ; Baccarani, U. ; Rossi, M. ; Berloco, P. ; Tanaka, K. ; Oike, F. ; Munn, S. ; Gane, E. ; Brekke, I. ; Boberg, K. M. ; Bernardos, A. ; Garcia, I. ; Cuervas, V. ; Moreno, J. M. ; Rimola, A. ; Cirera, I. ; Sanjuan, F. ; Prieto, M. ; Salcedo, M. ; Clemente, G. ; Ericson, B. ; Gjertsen, H. ; Herlenius, G. ; Kadry, Z. ; Mayer, D. ; Hayes, P. ; Davidson, J. ; Hodgson, J. ; Bynon, J. S. ; Davis, G. ; Ortiz, J. ; Manzarbeita, C. ; Mennon, R. ; Weisner, R. H. ; Wu, Y. ; Chensu, R. Y. ; Lake, J. R. ; Humar, A. / 12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus. In: Liver Transplantation. 2006 ; Vol. 12, No. 10. pp. 1464-1472.
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title = "12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus",
abstract = "The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neural) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level[predose])Co to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85{\%} of CsA-ME patients and 86{\%} o tacrolimus patients survived with a functioning grat (P not significant). Efficacy was similar in deceased-and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME 95/ 88,6{\%}) than with tacrolimus (14/85,16{\%}) (P< 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months was (13{\%} vs. 5{\%}, P< 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70{\%} vs. 49{\%}, P+ 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.",
author = "Gary Levy and Grazi, {Gian Luca} and Fernando Sanjuan and Youmin Wu and Ferdinand M{\"u}hlbacher and Didier Samuel and Styrbjorn Friman and Robert Jones and Guido Cantisani and Frederico Villamil and Umberto Cillo and Clavien, {Pierre Alain} and Goran Klintmalm and Gerd Otto and Stephen Pollard and McCormick, {P. Aiden} and V. Descalsi and A. Gadano and A. Villamil and P. Angus and S. Lynch and Balderson, {G. A.} and G. Jeffreys and B. Chester and R. Steininger and {de Hemptinne}, B. and R. Troisi and Zanotelli, {M. L.} and L. Leonardi and I. Boin and S. Mies and Guardia, {B. D.} and L. Lilly and P. Marotta and W. Wall and K. Peltekian and A. Roy and D. Marleau and C. Scudamore and M. Yoshida and J. Tchervenkov and M. Cantarovich and O. Boillot and P. Bernard and Y. Calmus and F. Conti and D. Cherqui and C. Duvoux and C. Ducerf and R. Maar and J. Gugenheim and A. Myx and D. Neau-Cransac and K. Mouette and F. Saliba and L. Rostaing and N. Kamar and C. Moench and M. O'Rourke and D. D'Amico and G. Varotti and A. Maffei-Faccioli and G. Gerunda and R. Merenda and A. Risaliti and U. Baccarani and M. Rossi and P. Berloco and K. Tanaka and F. Oike and S. Munn and E. Gane and I. Brekke and Boberg, {K. M.} and A. Bernardos and I. Garcia and V. Cuervas and Moreno, {J. M.} and A. Rimola and I. Cirera and F. Sanjuan and M. Prieto and M. Salcedo and G. Clemente and B. Ericson and H. Gjertsen and G. Herlenius and Z. Kadry and D. Mayer and P. Hayes and J. Davidson and J. Hodgson and Bynon, {J. S.} and G. Davis and J. Ortiz and C. Manzarbeita and R. Mennon and Weisner, {R. H.} and Y. Wu and Chensu, {R. Y.} and Lake, {J. R.} and A. Humar",
year = "2006",
month = "10",
doi = "10.1002/lt.20802",
language = "English (US)",
volume = "12",
pages = "1464--1472",
journal = "Liver Transplantation",
issn = "1527-6465",
publisher = "John Wiley and Sons Ltd",
number = "10",

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TY - JOUR

T1 - 12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplantation recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus

AU - Levy, Gary

AU - Grazi, Gian Luca

AU - Sanjuan, Fernando

AU - Wu, Youmin

AU - Mühlbacher, Ferdinand

AU - Samuel, Didier

AU - Friman, Styrbjorn

AU - Jones, Robert

AU - Cantisani, Guido

AU - Villamil, Frederico

AU - Cillo, Umberto

AU - Clavien, Pierre Alain

AU - Klintmalm, Goran

AU - Otto, Gerd

AU - Pollard, Stephen

AU - McCormick, P. Aiden

AU - Descalsi, V.

AU - Gadano, A.

AU - Villamil, A.

AU - Angus, P.

AU - Lynch, S.

AU - Balderson, G. A.

AU - Jeffreys, G.

AU - Chester, B.

AU - Steininger, R.

AU - de Hemptinne, B.

AU - Troisi, R.

AU - Zanotelli, M. L.

AU - Leonardi, L.

AU - Boin, I.

AU - Mies, S.

AU - Guardia, B. D.

AU - Lilly, L.

AU - Marotta, P.

AU - Wall, W.

AU - Peltekian, K.

AU - Roy, A.

AU - Marleau, D.

AU - Scudamore, C.

AU - Yoshida, M.

AU - Tchervenkov, J.

AU - Cantarovich, M.

AU - Boillot, O.

AU - Bernard, P.

AU - Calmus, Y.

AU - Conti, F.

AU - Cherqui, D.

AU - Duvoux, C.

AU - Ducerf, C.

AU - Maar, R.

AU - Gugenheim, J.

AU - Myx, A.

AU - Neau-Cransac, D.

AU - Mouette, K.

AU - Saliba, F.

AU - Rostaing, L.

AU - Kamar, N.

AU - Moench, C.

AU - O'Rourke, M.

AU - D'Amico, D.

AU - Varotti, G.

AU - Maffei-Faccioli, A.

AU - Gerunda, G.

AU - Merenda, R.

AU - Risaliti, A.

AU - Baccarani, U.

AU - Rossi, M.

AU - Berloco, P.

AU - Tanaka, K.

AU - Oike, F.

AU - Munn, S.

AU - Gane, E.

AU - Brekke, I.

AU - Boberg, K. M.

AU - Bernardos, A.

AU - Garcia, I.

AU - Cuervas, V.

AU - Moreno, J. M.

AU - Rimola, A.

AU - Cirera, I.

AU - Sanjuan, F.

AU - Prieto, M.

AU - Salcedo, M.

AU - Clemente, G.

AU - Ericson, B.

AU - Gjertsen, H.

AU - Herlenius, G.

AU - Kadry, Z.

AU - Mayer, D.

AU - Hayes, P.

AU - Davidson, J.

AU - Hodgson, J.

AU - Bynon, J. S.

AU - Davis, G.

AU - Ortiz, J.

AU - Manzarbeita, C.

AU - Mennon, R.

AU - Weisner, R. H.

AU - Wu, Y.

AU - Chensu, R. Y.

AU - Lake, J. R.

AU - Humar, A.

PY - 2006/10

Y1 - 2006/10

N2 - The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neural) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level[predose])Co to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% o tacrolimus patients survived with a functioning grat (P not significant). Efficacy was similar in deceased-and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME 95/ 88,6%) than with tacrolimus (14/85,16%) (P< 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months was (13% vs. 5%, P< 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70% vs. 49%, P+ 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

AB - The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neural) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level[predose])Co to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% o tacrolimus patients survived with a functioning grat (P not significant). Efficacy was similar in deceased-and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME 95/ 88,6%) than with tacrolimus (14/85,16%) (P< 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months was (13% vs. 5%, P< 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70% vs. 49%, P+ 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

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UR - http://www.scopus.com/inward/citedby.url?scp=33750112891&partnerID=8YFLogxK

U2 - 10.1002/lt.20802

DO - 10.1002/lt.20802

M3 - Article

C2 - 17004259

AN - SCOPUS:33750112891

VL - 12

SP - 1464

EP - 1472

JO - Liver Transplantation

JF - Liver Transplantation

SN - 1527-6465

IS - 10

ER -