title: 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.
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) (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 mumol/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.
authors.affiliation: University Health Network, Toronto General Hospital, Toronto, ON, Canada. glfgl2@attglobal.net
authors.forename: Gary
authors.initials: G
authors.lastname: Levy
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.forename: Fernando
authors.initials: F
authors.lastname: Sanjuan
authors.forename: Youmin
authors.initials: Y
authors.lastname: Wu
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mühlbacher
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Styrbjorn
authors.initials: S
authors.lastname: Friman
authors.forename: Robert
authors.initials: R
authors.lastname: Jones
authors.forename: Guido
authors.initials: G
authors.lastname: Cantisani
authors.forename: Federico
authors.initials: F
authors.lastname: Villamil
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.forename: Pierre Alain
authors.initials: PA
authors.lastname: Clavien
authors.forename: Goran
authors.initials: G
authors.lastname: Klintmalm
authors.forename: Gerd
authors.initials: G
authors.lastname: Otto
authors.forename: Stephen
authors.initials: S
authors.lastname: Pollard
authors.forename: P Aiden
authors.initials: PA
authors.lastname: McCormick
mesh_terms: D017677:Age Distribution; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology; D004655:Emulsions / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D016174:Hepacivirus / Q000302:isolation & purification*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016031:Liver Transplantation; D019520:Living Donors; D008137:Longitudinal Studies; D008297:Male; D008991:Monitoring, Physiologic; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004655:Emulsions; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D003404:Creatinine; D016559:Tacrolimus