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Article first published online: 26 SEP 2006
Copyright © 2006 American Association for the Study of Liver Diseases
Volume 12, Issue 10, pages 1464–1472, October 2006
How to Cite
Levy, G., Grazi, G. L., Sanjuan, F., Wu, Y., Mühlbacher, F., Samuel, D., Friman, S., Jones, R., Cantisani, G., Villamil, F., Cillo, U., Clavien, P. A., Klintmalm, G., Otto, G., Pollard, S. and McCormick, P. A. (2006), 12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus. Liver Transpl, 12: 1464–1472. doi: 10.1002/lt.20802
See Editorial on Page 1452
The trial was designed, overseen, and implemented with the support of the trial Steering Committee including representatives of the sponsor. Day-to-day operations were managed by Novartis Pharma AG. The study database is held by an independent data center, PRA International, Swansea, UK. The data center was responsible for statistical analysis of the data. Representatives of the sponsor have commented on the manuscript before submission for publication.
(For complete listing of investigators and centers, see Appendix)
- Issue published online: 26 SEP 2006
- Article first published online: 26 SEP 2006
- Manuscript Accepted: 12 MAR 2006
- Manuscript Received: 18 MAY 2005
- Novartis Pharma AG, Basel
The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 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% of tacrolimus patients survived with a functioning graft (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 (5/88, 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 (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. Liver Transpl 12:1464–1472, 2006. © 2006 AASLD.