This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long‐term outcomes with prolonged‐release tacrolimus versus tacrolimus BD in liver transplantation (January 2008–December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score‐matching for baseline demographics. Patients with <1 month of follow‐up were excluded from the analyses. In total, 4367 patients (prolonged‐release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score‐matched patients confirmed the significant survival advantages observed in the prolonged‐release tacrolimus‐ versus tacrolimus BD‐treated group. This large retrospective analysis from the ELTR identified significant improvements in long‐term graft and patient survival in patients treated with prolonged‐release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Background. Pharmacological preconditioning is one of the tools used to diminish preservation injury. We investigated the influence of sevoflurane preconditioning of liver grafts on postoperative graft function. Methods. Consecutive 60 deceased brain donors were randomized into sevoflurane group or control group. In sevoflurane group donors were treated with endexpiratory 2,0 volume% of sevoflurane during procurement. Primary endpoint was postoperative liver injury. Secondary endpoint was incidence of early allograft dysfunction (EAD). Results. The groups were not different in median DRI, donor age, graft steatosis, and MELD score. Peak AST and ALT levels were lower in sevoflurane group than in control group: 792 and 1861 (P = 0, 038) for AST and 606 and 1191 for ALT (P = 0, 117). Incidence of EAD was 16,7% in sevoflurane group and 50% in control group (Fisher test, P = 0, 013). In subgroups without steatosis preconditioning with sevoflurane did not have influence on incidence of EAD. In subgroups with mild and moderate steatosis incidence of EAD was lower in recipients of liver grafts treated with sevoflurane. Conclusions. Preconditioning with sevoflurane during organ procurement improves graft function by lowering incidence of early allograft dysfunction, particularly in recipients of steatotic liver grafts.

Summary The objectives of this study were to assess long‐term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once‐daily prolonged‐release tacrolimus‐based therapy. The study was a 5‐year non‐interventional prospective follow‐up of patients from the ADHERE study, a Phase IV 12‐month open‐label assessment of patients randomized to receive prolonged‐release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long‐term follow‐up, of whom 510 completed the study at year 5. At 1 year post‐transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5‐year acute rejection‐free survival rate was 77.4%, and biopsy‐confirmed acute rejection‐free survival rate was 86.0%. Renal function remained stable over the follow‐up period: mean ± SD eGFR 4‐variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m2 at 6 months and 52.5 ± 23.0 ml/min/1.73 m2 at 5 years post‐transplant. These findings support the role of long‐term once‐daily prolonged‐release tacrolimus‐based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.

Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged.

SUMMARYADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolongedrelease tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m 2 ; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2). 2017; 30: 83-95 Transplant International