Diapositiva 1

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LIS2T A multicenter randomized study comparing
Neoral C2 and tacrolimus in de novo liver
transplantationIncidence of Cardio-Vascular
Risk Factors at 1 year Post-Transplant A
Comparison between Patients Receiving
Cyclosporine or TacrolimusGL Grazi1, G Levy, O
Boillot, S Friman, G Cantisani, J Ortiz, S Lynch,
A McCormick, M Salcedo1Liver and Multi Organ
Transplant Unit, Bologna, ItalyOn behalf of the
LIS2T study group
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Background LIS2T Study design

• Multicenter 50 centers in 17 countries
  (Europe, North
• South America, Australia Japan)
• Randomized open-label, prospective, 6-month
  study

Neoral (C2 monitoring) n250
Screening and Transplant Stratification on HCV
status Randomization Within 24h post-transplant
Corticosteroids Azathioprine
Tacrolimus (C0 monitoring) n245
3 months Biopsy-provenacute rejection
6 months Efficacy safety
12 months Clinical statusrecorded
End-points
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Background Characteristic of donors and recipients
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Background All patients - Adverse Events by 6
Months
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Background Data Collected at 1 year
post-transplant

• Graft and patient survival
• Occurrence of malignancies between Month 6 and 12
• Episode of acute rejection between Month 6 and 12
• Immunosuppressant doses at 1 year
• Treatment received for lipid abnormalities,
  diabetes, hypertension
• Laboratory values (e.g. serum creatinine)
• Number of patients who provided data at 1 year
• CsA-ME n221/250, tacrolimus n223/245

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Background All patients - Treatment Received at 1
Year
p
Neoral C2
Tacrolimus
(n250)
(n245)

For diabetes
16
27

For dyslipidemia
5
3
n.s.
For hypertension
37
30

GL Grazi ATC 2005
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Study Design Aim of the Study

• To compare the presence of cardio-vascular risk
  factors at one year post-transplant in patients
  who received cyclosporine micro emulsion (CsA-ME)
  or tacrolimus (Tac)

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Study Design Aim of Study and Main Outcome
Measures

• Cardio-vascular risk factors
• Treatment at 1 year for new onset of
• Hypertension
• Hyperlipidemia
• Diabetes

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Study Design Patients

• Patients enrolled in LIS2T
• Patients who were not diagnosed with the
  condition at baseline.
• 1 year follow up
• Prospective data collectionRetrospective analysis

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Study Design Patients
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Results De Novo Hypertension at 1Year
P NS
12
Results De Novo Hyperlipidemia at 1 Year
P NS
13
Results De Novo Diabetes at 1 Year
P
14
Results Patients w/o condition at baseline
treated at 1year
All evaluable patients
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Results Patients w/o condition at baseline
treated at 1year
All evaluable patients Switcher excluded
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Conclusions

• A significantly higher proportion of de novo
  diabetes mellitus in patients receiving
  tacrolimus can still be observed at one year
  post-transplantation
• This condition is not transient
• No significant difference in the incidence of de
  novo hypertension or hyperlipidemia was observed

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Acknowledgements

• The LIS2T Investigator Study Group
• Argentina F Villamil A Gadano Australia R
  Jones, S Lynch, G Jeffreys. Austria F
  Muehlbacher, Belgium B de Hemptinne, Brazil G
  Cantisani, L Leonardi, S Mies, Canada G Levy, P
  Marotta, K Peltekian, A Roy, C Scudamore, J
  Tchervenkov, France O Boillot, Y Calmus, D
  Cherqui, C Ducerf, J Gugenheim, D Neau-Cransac, D
  Samuel, L Rostaing, Germany G Otto, Italy D
  DAmico, G L Grazi, A Maffei-Faccioli, A
  Risaliti, M Rossi, Japan K Tanaka, New Zealand
  S Munn, Norway I Brekke, Spain A Bernardos, V
  Cuervas, A Rimola, F Sanjuan, M Salcedo, Sweden
  B Ericzon, S Friman, Switzerland P A Clavien,
  United Kingdom D Mayer, A McCormick, P Hayes, S
  Pollard, United States J S Bynon, G Klintmalm, J
  Ortiz, R Mennon, Y Wu, JR Lake