title: Do patient characteristics influence efficacy and renal outcomes in liver transplant patients receiving everolimus?
abstract: Data from the 24-month randomized, multicenter, open-label H2304 study in 719 de novo liver transplant recipients were analyzed to evaluate the influence of variables potentially affecting immunological or renal response: recipient age, gender, end-stage disease, hepatitis C virus (HCV) status, and Model for End-stage Liver Disease score and estimated glomerular filtration rate (eGFR) at randomization (day 30). Treated BPAR was similar between everolimus with reduced tacrolimus (EVR + Reduced TAC) vs. conventional tacrolimus-based therapy (TAC Control) in all subpopulations, with a trend to lower risk under everolimus with reduced tacrolimus (EVR + Reduced TAC) in patients < 60 yrs and HCV-negative recipients. Risk of graft loss or death was similar in both treatment groups for all subpopulations. The change in eGFR to month 24 showed a benefit for EVR + Reduced TAC vs. TAC Control in all subpopulations other than those with the lowest baseline eGFR (30 to < 55 mL/min/1.73 m(2)), with a significant difference in favor of EVR + Reduced TAC for younger recipients (< 60 yr), female patients, HCV-negative patients and those with baseline eGFR of 55 to < 70 mL/min/1.73 m(2). Everolimus with reduced tacrolimus maintains efficacy to at least two yr after liver transplantation even in patients with risk factors for rejection, with particular renal benefits in specific patient subpopulations.
authors.affiliation: Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Simone
authors.affiliation: Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Dong
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Cesar
authors.initials: C
authors.lastname: Escrig
authors.affiliation: Department of Hepatobiliary Surgery and Transplantation, University Medical Center Eppendorf, Hamburg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
mesh_terms: D058625:End Stage Liver Disease / Q000145:classification* / Q000601:surgery*; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus
keywords: calcineurin inhibitor; efficacy; everolimus; glomerular filtration rate; liver transplantation; mTOR inhibitor; randomized; rejection; renal function; tacrolimus