Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis

AbstractBackgroundThe clinical perspective on hepatic growth is limited. The goal of the present study was to compare hepatic hypertrophy and the kinetic growth rate(KGR) in patients after the ALPPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) procedure, portal vein embolization (PVE) and living donor liver transplantation.MethodsVolumetry and KGR of the future liver remnant (FLR) were compared from (15) patients undergoing ALPPS, (53) patients undergoing PVE, (90) recipients of living donor liver grafts and (93) donors of living donor liver grafts.ResultsThe degree of hypertrophy was significantly greater after ALPPS (84.3 ± 7.8%) than after PVE (36.0 ± 27.2%) (P < 0.001). The KGR was also significantly greater for ALPPS [32.7 ± 13.6 cubic centimetres (cc)/day] (10.8 ± 4.5%/day) compared with PVE (4.4 ± 3.2 cc/day) (0.98 ± 0.75%/day) (P < 0.001). The FLR of living donor donors had the greatest degree of hypertrophy (107.5 ± 39.2%) and was greater than after ALPPS (P = 0.02), PVE (P < 0.001) and in living donor‐recipient grafts (P < 0.001). KGR (cc/day) was greater in FLR of living donor donors compared with both ALPPS (P < 0.001) and PVE (P < 0.001). The KGR in patients undergoing ALPPS and living donor liver transplantation had a linear relationship with the size of FLR.ConclusionFLR hypertrophy and KGR were greater after ALPPS than PVE. However, the degree of hypertrophy after ALPPS is not unprecedented, as KGR in the FLR from living donor donors is equal to or greater than after ALPPS. The KGR of the FLR in patients after ALPPS and living donor donors correlates directly with the size of the FLR

Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND AND AIM Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation

BACKGROUND: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups. METHODS: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75(th)-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort

Introducing Machine Perfusion into Routine Clinical Practice for Liver Transplantation in the United States: The Moment Has Finally Come

While adoption of machine perfusion technologies into clinical practice in the United States has been much slower than in Europe, recent changes in the transplant landscape as well as device availability following FDA approval have paved the way for rapid growth. Machine perfusion may provide one mechanism to maximize the utilization of potential donor liver grafts. Indeed, multiple studies have shown increased organ utilization with the implementation of technologies such as ex-situ normothermic machine perfusion (NMP), ex-situ hypothermic machine perfusion (HMP) and in-situ normothermic regional perfusion (NRP). The current review describes the history and development of machine perfusion utilization in the Unites States along with future directions. It also describes the differences in landscape between Europe and the United States and how this has shaped clinical application of these technologies

Effects of the Share 35 Rule on Waitlist and Liver Transplantation Outcomes for Patients with Hepatocellular Carcinoma.

Several studies have investigated the effects following the implementation of the "Share 35" policy; however none have investigated what effect this policy change has had on waitlist and liver transplantation (LT) outcomes for hepatocellular carcinoma(HCC).Data were obtained from the UNOS database and a comparison of the 2 years post-Share 35 with data from the 2 years pre-Share 35 was performed.In the pre-Share35 era, 23% of LT were performed for HCC exceptions compared to 22% of LT in the post-Share35 era (p = 0.21). No difference in wait-time for HCC patients was seen in any of the UNOS regions between the 2 eras. Competing risk analysis demonstrated that HCC candidates in post-Share 35 era were more likely to die or be delisted for "too sick" while waiting (7.2% vs. 5.3%; p = 0.005) within 15 months. A higher proportion of ECD (p<0.001) and DCD (p<0.001) livers were used for patients transplanted for HCC, while lower DRI organs were used for those patients transplanted with a MELD≥35 between the 2 eras (p = 0.007).No significant change to wait-time for patients listed for HCC was seen following implementation of "Share 35". Transplant program behavior has changed resulting use of higher proportion of ECD and DCD liver grafts for patients with HCC. A higher rate of wait list mortality was observed in patients with HCC in the post-Share 35 era

Bias-corrected estimates of reduction of post-surgery length of stay and corresponding cost savings through the widespread national implementation of fast-tracking after liver transplantation: a quasi-experimental study

Background: Fast-tracking is an approach adopted by Mayo Clinic in Florida’s (MCF) liver transplant (LT) program, which consists of early tracheal extubation and transfer of patients to surgical ward, eliminating a stay in the intensive care unit in select patients. Since adopting this approach in 2002, MCF has successfully fast-tracked 54.3% of patients undergoing LT. Objectives: This study evaluated the reduction in post-operative length of stay (LOS) that resulted from the fast-tracking protocol and assessed the potential cost saving in the case of nationwide implementation. Methods: A propensity score for fast-tracking was generated based on MCF liver transplant databases during 2011–2013. Various propensity score matching algorithms were used to form control groups from the United Network of Organ Sharing Standard Analysis and Research (STAR) file that had comparable demographic characteristics and health status to the treatment group identified in MCF. Multiple regression and matching estimators were employed for evaluation of the post-surgery LOS. The algorithm generated from the analysis was also applied to the STAR data to determine the proportion of patients in the US who could potentially be candidates for fast-tracking, and the potential savings. Results: The effect of the fast-tracking on the post-transplant LOS was estimated at approximately from 2.5 (p-value = 0.001) to 3.2 (p-value \u3c 0.001) days based on various matching algorithms. The cost saving from a nationwide implementation of fast-tracking of liver transplant patients was estimated to be at least $78 million during the 2-year period. Conclusion: The fast-track program was found to be effective in reducing post-transplant LOS, although the reduction appeared to be less than previously reported. Nationwide implementation of fast-tracking could result in substantial cost savings without compromising the patient outcome