Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

Background. Portal vein thrombosis (PVT) has been seen as an obstacle to liver transplantation (LTx). Recent data suggest that favorable results may be achieved in this group of patients but only limited information from small size series is available. The present study was conducted in an effort to review the surgical options in patients with PVT and to assess the impact of PVT on LTx outcome. Risk factors for PVT and the value of screening tools are also analyzed. Methods. Adult LTx performed from 1987 through 1996 were reviewed. PVT was retrospectively graded according to the operative findings: grade 1: 50% PVT; grade 3: complete PV and proximal SMV thrombosis; grade 4: complete PV and entire SMV thrombosis. Results. Of 779 LTx, 63 had operatively confirmed PVT (8.1%): 24 had grade 1, 23 grade 2, 6 grade 3, and 10 grade 4 PVT. Being male, treatment for portal hypertension, Child-Pugh class C, and alcoholic liver disease were associated with PVT. Sensitivity of ultrasound (US) in detecting PVT increased with PVT grade and was 100% in grades 3–4. In patients with US-diagnosed PVT, an angiogram was performed and ruled out a false positive US diagnosis in 13%. In contrast with US, angiograms differentiated grade 1 from grade 2, and grade 3 from grade 4 PVT. Grade 1 and 2 PVT were managed by low dissection and/or a thrombectomy; in grade 3 the distal SMV was directly used as an inflow vessel, usually through an interposition donor iliac vein; in grade 4 a splanchnic tributary was used or a thrombectomy was attempted. Transfusion requirements in PVT patients (10 U) were higher than in non-PVT patients (5 U) (P <0.01). In-hospital mortality for PVT patients was 30% versus 12.4% in controls (P <0.01). Patients with PVT had more postoperative complications, renal failure, primary nonfunction, and PV rethrombosis. The overall actuarial 5-year patient survival rate in PVT patients (65.6%) was lower than in controls (76.3%;P =0.04). Patients with grade 1 PVT, however, had a 5-year survival rate (86%) identical to that of controls, whereas patients with grades 2, 3, and 4 PVT had reduced survival rates. The 5-year patient survival rate improved from the 1st to the 2nd era in non-PVT patients (from 72% to 83%;P <0.01), in grade 1 PVT (from 53% to 100%;P <0.01), and in grades 2 to 4 PVT (from 38% to 62%;P =0.11). Conclusions. The value of US diagnosis in patients with PVT depends on the PVT grade, and false negative diagnoses occur only in incomplete forms of PVT (grades 1–2). The degree of PVT dictates the surgical strategy to be used, thrombectomy/low dissection in grade 1–2, mesoportal jump graft in grade 3, and a splanchnic tributary in grade 4. Taken altogether, PVT patients undergo more difficult surgery, have more postoperative complications, have higher in-hospital mortality rates, and have reduced 5-year survival rates. Analysis by PVT grade, however, reveals that grade 1 PVT patients do as well as controls; only grades 2 to 4 PVT patients have poorer outcomes. With increased experience, results of LTx in PVT patients have improved and, even in severe forms of PVT, a 5-year survival rate >60% can now be achieved.

The purpose of this registry study was to provide an overview of trends and results of liver transplantation in Europe from 1968 to 2016. This data on liver transplantation (LT) was collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in liver transplantation in Europe over more than 5 decades; something that cannot be obtained from only a single center experience.

We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.