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Objective: To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion., Background: Despite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary nonfunction. Effective strategies preventing such outcomes are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to 2 weeks and providing a unique window of opportunity for defatting before transplantation., Methods: Over a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ normothermic machine perfusion. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents were measured simultaneously., Results: Of 51 liver grafts, 20 were steatotic, with up to 85% macrovesicular steatosis, and were perfused for up to 12 days. Ten livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic functions remained preserved for most grafts until perfusion ended., Conclusion: Ex situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute., Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics., Results: Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P =0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P =0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P =0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P =0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria., Conclusions: This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Maximizing patient and allograft survival after liver transplant (LT) is important from both a patient care and organ utilization perspective. Although individual studies have addressed the effects of short-term post-LT complications on a limited scale, there has not been a systematic review of the literature formally assessing the potential effects of early complications on long-term outcomes., Objectives: To identify whether short-term complications after LT affect allograft and overall survival, to identify short-term complications of particular clinical interest and significance, and to provide recommendations to improve post-LT graft and patient survival., Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central., Methods: A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel., Results: The literature review and analysis provided show that short-term complications have a large impact on allograft and patient survival after LT. The complications with the strongest effect on survival are acute kidney injury (AKI), biliary complications, and early allograft dysfunction (EAD)., Conclusion: This panel recommends taking measures to reduce the risk and incidence of short-term complications post-LT. Clinicians should pay particular attention to preventing or ameliorating AKI, biliary complications, and EAD (Quality of evidence; Moderate | Grade of Recommendation; Strong)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Morphometric features such as the Milan criteria serve as standard criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Since it has been recognized that these criteria are too restrictive and do not adequately display the tumor biology, additional selection parameters are emerging. Methods: Concise review of the current literature on patient selection for downstaging and LT for HCC outside the Milan criteria. Results: The major task in patients outside the Milan criteria is the need for higher granularity with patient selection, since the benefit through LT is not uniform. The recent literature clearly shows that beneath tumor size and number, additional selection parameters are useful in the process of patient selection for and during downstaging. For initial patient selection, the alpha fetoprotein (AFP) level adds additional information to the size and number of HCC nodules concerning the chance of successful downstaging and LT. This effect is quantifiable using newer selection tools like the WE (West-Eastern) downstaging criteria or the Metroticket 2.0 criteria. Also an initial PET-scan and/or tumor biopsy can be helpful, especially in the high risk group of patients outside the University of California San Francisco (UCSF) criteria. After this entry selection, the clinical course during downstaging procedures concerning the tumor and the AFP response is of paramount importance and serves as an additional final selection tool. Conclusion: Selection criteria for liver transplantation in HCC patients are becoming more and more sophisticated, but are still imperfect. The implementation of molecular knowledge will hopefully support a more specific risk prediction for HCC patients in the future, but do not provide a profound basis for clinical decision-making at present., Competing Interests: DS has received honoraria or consultation fees from BTG, Johnson & Johnson, Gubert, Novartis, Olympus, and SIRTEX; and has participated in the following company's sponsored speaker's bureaus: Abbvie, Astellas, Bayer, BTG, Eisai, Johnson & Johnson, MSD/Merck, Novartis, and Olympus. GS has received research grants from Bayer and Roche, and consultancy fees from AstraZeneca and Roche. J-CN has received research grants from Bayer for INSERM UMR 1138. TB declares the following grants/research support: Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Novartis, Sequana Medical. TB has received honoraria or consultation fees from Abbvie, Alexion, Bayer, Gilead, Eisai, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi; and has participated in the following company's sponsored speaker's bureaus: Abbvie, Alexion, Bayer, Gilead, Eisai, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Sequana Medica, and SIRTEX. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seehofer, Petrowsky, Schneeberger, Vibert, Ricke, Sapisochin, Nault and Berg.)

De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective., Background: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature., Study Design: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival., Results: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT., Conclusion: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to maintain long-term full function and viability of partial livers perfused ex situ for sufficient duration to enable ex situ treatment, repair, and regeneration., Background: Organ shortage remains the single most important factor limiting the success of transplantation. Autotransplantation in patients with nonresectable liver tumors is rarely feasible due to insufficient tumor-free remnant tissue. This limitation could be solved by the availability of long-term preservation of partial livers that enables functional regeneration and subsequent transplantation., Methods: Partial swine livers were perfused with autologous blood after being procured from healthy pigs following 70% in-vivo resection, leaving only the right lateral lobe. Partial human livers were recovered from patients undergoing anatomic right or left hepatectomies and perfused with a blood based perfusate together with various medical additives. Assessment of physiologic function during perfusion was based on markers of hepatocyte, cholangiocyte, vascular and immune compartments, as well as histology., Results: Following the development phase with partial swine livers, 21 partial human livers (14 right and 7 left hemi-livers) were perfused, eventually reaching the targeted perfusion duration of 1 week with the final protocol. These partial livers disclosed a stable perfusion with normal hepatic function including bile production (5-10 mL/h), lactate clearance, and maintenance of energy exhibited by normal of adenosine triphosphate (ATP) and glycogen levels, and preserved liver architecture for up to 1 week., Conclusion: This pioneering research presents the inaugural evidence for long-term machine perfusion of partial livers and provides a pathway for innovative and relevant clinical applications to increase the availability of organs and provide novel approaches in hepatic oncology., Competing Interests: Conflict of interest: E.T.H. (Swiss Federal Institute of Technology in Zurich) (M. H., M. J. S., B. B., P. RvR., D.B.) and the University of Zurich (D.E., P.D., L.B.B. and P-A. C.) own/applied for patents on liver perfusion technology (PCT/EP2019/051252, PCT/EP20 17/068506). The authors report no other conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25-30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure., Purpose: The aim of this review is to depict the various interventions for liver parenchyma augmentation-assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates., Conclusions: To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly "palliative" disease into a curative and sometimes in a "chronic" disease., (© 2021. The Author(s).)

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty., Competing Interests: Conflict of interest PB declares no conflict of interest with any financial organization regarding the manuscript, however she received fees from Biotest, Germany, Kedrion, Italy and Chiesi Farmaceutici, Italy. DS declares no conflict of interest with any financial organization regarding the manuscript, however he received fees from Biotest, Germany and Goliver Therapeutics, France. CD declares no conflict of interest with any commercial organization regarding the manuscript, however he received fees from Biotest, Germany. NT has institutional grant support from Gilead Sciences, USA and Genentech/Roche, USA. RJ has research collaborations with Yaqrit Limited, UK and Takeda, Japan. He is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma, UK. He is also the founder of Yaqrit Limited, a spin out company from University College London. VS, HP declare no conflict of interest with any commercial organization. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Liver transplantation (LT) in Europe became an established life-saving treatment for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver conditions with life-threatening hepatic dysfunction. Although there are substantial disparities in donation and transplant rates among European countries, LT can be offered to almost every European citizen today. In order to maximize the LT benefit beyond national levels, many countries cooperate within transnational organizations including Eurotransplant, Scandiatransplant, and Southern Alliance for Transplantation. In the majority of European countries, liver allocation is based on the Model for End-Stage Liver Disease (MELD). Similar to North America, the ongoing extinction of hepatitis C and increase of non-alcoholic steatohepatitis are also a hallmark of change in LT indications in Europe. Apart from Turkey, the organ pool for LT in European countries is mainly based on organs from donors after brain death, although some countries retrieve a substantial proportion of organs from donors after circulatory death. According to the 2018 report of the European Liver Transplant Registry, 146,762 LT have been performed in Europe until 2016. In the most recent period, LT in Europe achieved respectable 1- and 5-year overall survival rates of 86% and 74%., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes., Methods: Given the waitlist outcomes (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the Transplant Index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation)., Results: Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low TI groups (TI 10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9%, respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates., Conclusions: The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation.

Although aortohepatic conduits (AHCs) provide an effective technique for arterialization in liver transplantation (LT) when the native recipient artery is unusable, various publications report higher occlusion rates and impaired outcome compared to conventional anastomoses. This systematic review and meta-analysis investigates the published evidence of outcome and risk of AHCs in LT using bibliographic databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Primary and secondary outcome were artery occlusion as well as graft and patient survival. Twenty-three retrospective studies were identified with a total of 22 113 patients with LT, of whom 1900 patients (9%) received an AHC. An AHC was used in 33% of retransplantations. Early artery occlusion occurred in 7% (3%-16%) of patients with AHCs, compared to 2% (1%-3%) without conduit (OR 3.70; 1.63-8.38; P = .001). The retransplantation rate after occlusion was not significantly different in both groups (OR 1.46; 0.67-3.18; P = .35). Graft (HR 1.38; 1.17-1.63; P < .001) and patient (HR 1.57; 1.12-2.20; P = .009) survival was significantly lower in the AHC compared to the nonconduit group. In contrast, graft survival in retransplantations was comparable (HR 1.00; 0.82-1.22; P = .986). Although AHCs provide an important rescue option, when regular revascularization is not feasible during LT, transplant surgeons should be alert of the potential risk of inferior outcome., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Although the type of hepatic artery revascularization technique is known to have an impact on patency rates, independent perioperative risk factors on patient outcomes are poorly defined. All consecutive adult patients undergoing cadaveric liver transplantation (n = 361) from July 2007 to June 2016 in a single institution were analyzed. Primary outcomes were early (<30 days) hepatic artery occlusion and primary hepatic artery patency rate. A multivariate model was used to identify independent risk factors for occlusion and the need of arterial conduit, as well as their impact on graft and patient survival. Arterial revascularization without additional reconstruction (end-to-end arterial anastomosis [AA]) was performed in 77% (n = 279), arterial reconstruction (AR) in 15% (n = 53), and aortohepatic conduit (AHC) in 8% (n = 29) of patients. AHC had the highest mean intraoperative flow (275 mL/minute; P = 0.02) compared with AA (250 mL/minute) and AR (200 mL/minute; P = 0.02). There were 43 recipients (12%) who had an occlusive event with successful revascularization in 20 (47%) recipients. One-year primary patency rates of AA, AR, and AHC were 97%, 88%, and 74%, respectively. Aortic calcification had an impact on early occlusion. AR (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.26-10.75; P = 0.02) and AHC (OR, 6.21; 95% CI, 2.02-18.87; P = 0.001) were independent risk factors for early occlusion. Dyslipidemia additionally independently contributed to early occlusion (OR, 2.74; 95% CI, 0.96-7.87; P = 0.06). The 1- and 5-year graft survival rates were 83% and 70% for AA, 75% and 69% for AR, and 59% and 50% for AHC (P = 0.004), respectively. In conclusion, arterial patency is primarily determined by the type of vascular reconstruction rather than patient or disease characteristics. The preoperative lipid status is an independent risk factor for early occlusion, whereas overall occlusion is only based on the performed vascular reconstruction, which is also associated with reduced graft and patient survival. Liver Transplantation 24 790-802 2018 AASLD., (© 2018 by the American Association for the Study of Liver Diseases.)

Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for "equity", trying to save every patient, regardless of the overall utility; and "efficiency", rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose "absolute" and "relative" conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

: This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients., Objective: To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups., Background: Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative., Methods: Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff., Results: Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values., Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To identify medical predictors of futility in recipients with laboratory Model of End-Stage Liver Disease (MELD) scores of 40 or more at the time of orthotopic liver transplantation (OLT)., Background: Although the survival benefit for transplant patients with the highest MELD scores is indisputable, the medical and economic effort to bring these highest acuity recipients through OLT presents a major challenge for every transplant center., Methods: This study was undertaken to analyze outcomes in patients with MELD scores of 40 or more undergoing OLT during the period February 2002 to December 2010. The analysis was focused on futile outcome (3-month or in-hospital mortality) and long-term posttransplant outcome. Independent predictors of futility and failure-free survival were identified and a futility risk model was created., Results: During the study period, 1522 adult cadaveric OLTs were performed, and 169 patients (13%) had a MELD score of 40 or more. The overall 1, 3, 5, and 8-year patient survivals were 72%, 64%, 60%, and 56%. Futile outcome occurred in 37 patients (22%). MELD score, pretransplant septic shock, cardiac risk, and comorbidities were independent predictors of futile outcome. Using all 4 factors, the futility risk model had a good discriminatory ability (c-statistic 0.75). Recipient age per year, life-threatening postoperative complications, hepatitis C, and metabolic syndrome were independent predictors for long-term survival in nonfutile patients (Harrels c-statistic 0.72)., Conclusions: Short- and long-term outcomes of recipients with MELD scores of 40 or more are primarily determined by disease-specific factors. Cardiac risk, pretransplant septic shock, and comorbidities are the most important predictors and can be used for risk stratification in these highest acuity recipients.

Up to 23% of liver allografts fail post-transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high-risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49,288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0-7), month (20%, day 8-30), and year (33%, day 31-365). Only retransplantation within the first year (day 0-365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high-risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Importance: While orthotopic liver transplantation (OLT) is a durable life-saving treatment for patients with irreversible liver disease, the waiting list mortality rate for children younger than 6 years is 4 times higher than for children aged 11 to 17 years and adults owing to scarce availability of size-appropriate grafts for transplantation., Objective: To compare long-term outcomes for children (aged ≤18 years) undergoing OLT using grafts from donation after circulatory death (DCD) and donation after brain death (DBD)., Design, Setting, and Participants: Retrospective study using case-control matched groups at a university transplant center. All patients aged 18 years and younger who underwent OLT using DCD organs between February 1, 1990, and November 30, 2010, at the University of California, Los Angeles, were matched in a 1 to 3 ratio with patients who received primary OLT from DBD donors within a 12-month period. Other matching criteria included recipient age, weight, cause of liver disease, and acuity of illness. Outcomes after OLT were compared for DCD (n = 7) and DBD (n = 21) donors. The median follow-up was 4.5 years., Main Outcomes and Measures: The primary outcome measure was graft failure-free survival; the secondary end point was the development of ischemic cholangiopathy., Results: Comparing DCD and DBD groups, recipient median age (28.4 vs 20.1 months, respectively; P = .80), weight (12.0 vs 11.6 kg, respectively; P = .87), Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score (19 vs 11, respectively; P = .48), and donor age (24.0 vs 13.1 months, respectively; P = .72) were similar. For the DCD donors, the median donor warm ischemia duration was 24 minutes. Liver test results were similar for both groups at 1 week and 3, 6, and 12 months following OLT. Ten-year patient and graft survival rates for both DCD and DBD were 100%. Neither ischemic cholangiopathy nor vascular complications occurred in the DCD group. Biliary anastomotic strictures occurred in 1 DCD patient and 3 DBD patients., Conclusions and Relevance: Our study showed excellent long-term outcomes with liver transplantation in children using DCD organs. Use of liver grafts procured after circulatory death is an effective approach to expand the donor pool and remains an untapped resource for children with end-stage liver disease.

Objective: To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure., Background: The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity., Methods: Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified., Results: Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival., Conclusions: We present the world's largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the "sickest first" allocation approach.

Background: Blood loss during liver transplantation is not incorporated into the dominant models for post-transplant survival. Our objective was to investigate blood transfusion requirement as a risk factor for mortality after liver transplantation, and to further analyze risk factors for intraoperative blood transfusion requirement and hepatectomy time., Study Design: We conducted a retrospective analysis of 233 consecutive liver transplant recipients over a span of 3 years by a single experienced surgeon. Mean follow-up was 2.5 years. Independent risk factors for patient survival after liver transplantation were identified using Cox proportion hazard regression. Independent risk factors for intraoperative blood transfusion requirement and hepatectomy time were identified using logistic regression., Results: Two factors were identified as significant predictors in multivariate analysis for survival after liver transplantation: hepatocellular carcinoma (hazard ratio [HR] 1.9, 95% CI 1.1 to 3.2) and intraoperative blood transfusion requirement per unit (HR 1.01, 95% CI 1.0 to 1.02). Threshold analysis revealed that intraoperative blood transfusion volume ≥28 units or 85(th) percentile (HR 2.5, 95% CI 1.3 to 4.7) was a significant risk factor for patient survival. Four covariates were identified as significant risk factors for intraoperative blood requirement: warm ischemia time (odds ratio [OR] 1.12, 95% CI 1.06 to 1.18), bilirubin (OR 1.04, 95% CI 1.02 to 1.08), previous surgery (OR 1.7, 95% CI 1.02 to 2.9), and hepatectomy time (OR 1.01, 95% CI 1.00 to 1.02). The only risk factor for prolonged hepatectomy time was previous major abdominal surgery (OR 4.0, 95% CI 1.7 to 9.5)., Conclusions: Intraoperative blood transfusion requirement is an important risk factor for mortality after liver transplantation. The strongest risk factors for intraoperative blood transfusion requirement are warm ischemia time and bilirubin levels. Intraoperative blood loss and its risk factors should be incorporated into models to predict survival after liver transplantation., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Our aim was to analyze our single-center experience with orthotopic liver transplantation for metabolic lethal genetic syndromes in children and adults., Study Design: From 1984 to 2012, all pediatric (younger than 18 years) and adult (18 years and older) patients who underwent orthotopic liver transplantation for lethal genetic disorders were identified. Data on diagnostic pathways and specific outcomes were analyzed for both groups. Outcomes measures included recurrence rate as well as graft and patient survival., Results: Metabolic lethal genetic syndrome was the primary indication for orthotopic liver transplantation in 152 of 4,564 patients (3.3%) at University of California, Los Angeles during the study period (74 pediatric patients and 78 adults). Genetic testing was performed in only 12% of the 152 patients and in 39% of patients after 2006. Two patients (1.3%) experienced a recurrence of the genetic disease. Overall 5- and 20-year survival rates were 89% and 77% for children and 73% and 50% for adults. Survival of pediatric patients was superior to adults (log-rank p < 0.009). Multivariate analysis identified age (hazard ratio = 2.18), preoperative life support (hazard ratio = 2.68), and earlier transplantation (hazard ratio = 3.41) as independent predictors of reduced survival., Conclusions: Orthotopic liver transplantation achieved excellent long-term survival in pediatric and adult patients with lethal genetic syndromes and represents a model of personalized genomic medicine by providing gene therapy through solid organ transplantation., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

An accurate clinical assessment of hepatic steatosis before transplantation is critical for successful outcomes after liver transplantation, especially if a pathologist is not available at the time of procurement. This prospective study investigated the surgeon's accuracy in predicting hepatic steatosis and organ quality in 201 adult donor livers. A steatosis assessment by a blinded expert pathologist served as the reference gold standard. The surgeon's steatosis estimate correlated more strongly with large-droplet macrovesicular steatosis [ld-MaS; nonparametric Spearman correlation coefficient (rS ) = 0.504] versus small-droplet macrovesicular steatosis (sd-MaS; rS  = 0.398). True microvesicular steatosis was present in only 2 donors (1%). Liver texture criteria (yellowness, absence of scratch marks, and round edges) were mainly associated with ld-MaS (variance = 0.619) and were less associated with sd-MaS (variance = 0.264). The prediction of ≥30% ld-MaS versus <30% ld-MaS was excellent when liver texture criteria were used (accuracy = 86.2%), but it was less accurate when the surgeon's direct estimation of the steatosis percentage was used (accuracy = 75.5%). The surgeon's quality grading correlated with the degree of ld-MaS and the surgeon's steatosis estimate as well as the incidence of poor initial function and primary nonfunction. In conclusion, the precise estimation of steatosis remains challenging even in experienced hands. Liver texture characteristics are more helpful in identifying macrosteatotic organs than the surgeon's actual perception of steatosis. These findings are especially important when histological assessment is not available at the donor's hospital., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Ischaemia-reperfusion injury (IRI) in the liver, a major complication of haemorrhagic shock, resection and transplantation, is a dynamic process that involves the two interrelated phases of local ischaemic insult and inflammation-mediated reperfusion injury. This Review highlights the latest mechanistic insights into innate-adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischaemia-reperfusion, discusses progress in large animal experiments and examines efforts to minimize liver IRI in patients who have received a liver transplant. The interlinked signalling pathways in multiple hepatic cell types, the IRI kinetics and positive versus negative regulatory loops at the innate-adaptive immune interface are discussed. The current gaps in our knowledge and the pathophysiology aspects of IRI in which basic and translational research is still required are stressed. An improved appreciation of cellular immune events that trigger and sustain local inflammatory responses, which are ultimately responsible for organ injury, is fundamental to developing innovative strategies for treating patients who have received a liver transplant and developed ischaemia-reperfusion inflammation and organ dysfunction.

Objective: To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH)., Summary of Background Data: With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited., Methods: We conducted an analysis from our prospective database of 144 adult NASH patients who underwent LT between December 1993 and August 2011. Outcomes and resource utilization were compared with other common indications for LT. Independent predictors of graft and patient survival were identified., Results: The average Model for End-Stage Liver Disease score was 33. The frequency of NASH as the primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the second most common indication for LT at our center behind hepatitis C. NASH patients had significantly longer operative times (402 vs 322 minutes; P < 0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001), and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5-year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable with other diagnoses. Age greater than 55 years, pretransplant intubation, dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor age greater than 55 years, and cold ischemia time greater than 550 minutes were significant independent predictors of survival for all patients, whereas body mass index greater than 35 was a predictor in NASH patients only., Conclusions: We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.

Objective: To develop a prognostic scoring system for risk stratification of patients with hepatic graft failure (GF) undergoing retransplants of the liver (ReLT) and improve patient selection., Summary of Background Data: Retransplantation of the liver remains controversial because of inferior outcomes compared with the primary orthotopic liver transplantation (OLT) and raises concerns of inappropriate utilization of a scarce donor organ resource. Data on risk stratification of ReLT patients for long-term survival outcomes are limited., Methods: We conducted an analysis from our prospective database of 466 adults' ReLT between February 1984 and September 2010. Mean follow-up was 3 years. Each independent predictor for allograft failure was assigned risk score (RS) points of 1 or 2, proportional to the corresponding parameter estimate under the Cox model: Predictive index category (PIC) 1, RS = 0; PIC II, RS = 1 to 2; PIC III, RS = 3 to 4; and PIC IV, RS = 5 to 12., Results: Eight risk factors predictive for GF after ReLT included recipient age greater than 55 years, Model for End-Stage Liver Disease score greater than 27, history of prior OLT greater than 1, pre-ReLT requirement for mechanical ventilation, serum albumin less than 2.5 g/dL, donor age greater than 45 years, intraoperative requirement of packed red blood cell transfusion greater than 30 units, and performance of ReLT between 15 and 180 days from the prior OLT. Five-year GF-free survival was significantly higher in PIC I (65%) than in PIC II (53%), PIC III (43%), and PIC IV (20%) groups (P < 0.001)., Conclusions: This risk-stratification model was highly predictive of long-term outcome after liver retransplantation in adult recipients. This formula provides a practical guide for selection of candidates for retransplantation of the liver that can lead to improved patient outcomes and optimal utilization of a scarce resource.

Objective: To define a prognostic scoring system for risk stratification of patients undergoing orthotopic liver transplantation (OLT) using grafts from donation after cardiac death (DCD)., Design: Retrospective study., Setting: University transplant center., Patients: Eighty-one patients underwent OLT using DCD grafts from March 1, 1994, to November 30, 2010. The mean follow-up was 2 years. Independent risk factors for graft failure after OLT were identified using Cox model and assigned risk score points. Points were summed and assigned to predictive index categories: 0 or 1 for low risk, 2 to 4 for intermediate risk, and 5 to 9 for high risk., Results: Six multivariate factors predictive for graft failure after OLT using DCD grafts included the following: for recipients, (1) diagnosis of hepatitis C virus with malignancy, non-hepatitis C virus with malignancy, or hepatitis C virus only, (2) previous OLT, and (3) body mass index (calculated as weight in kilograms divided by height in meters squared) greater than 30; for donors, (4) hepatitis B core antibody positivity and (5) mean arterial pressure lower than 60 mm Hg for longer than 20 minutes after withdrawal of life support; and for grafts, (6) cold ischemia time longer than 6 hours. Five-year graft failure-free survival was significantly higher for the low-risk group (83%) compared with the intermediate-risk (62%) and high-risk (0%) groups (P < .001). Overall biliary complications occurred in 24 patients (29%), with ischemic cholangiopathy in 8 patients (9.9%)., Conclusions: Our study showed superior long-term patient survival with liver transplantation using DCD organs in highly selected donors and recipients. We propose a practical risk stratification system highly predictive of long-term survival outcomes after OLT using DCD grafts. Application of this predictive index for transplant candidates receiving DCD liver grafts would improve patients' outcomes and optimize use of scarce resources.

Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: (1) the need for an expanded number of useable donor organs, (2) the need for improved therapies to treat recurrent hepatitis C after transplantation and (3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma., (© 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To compare the survival difference between 2 surgical modalities in the treatment of locally advanced intrahepatic and hilar cholangiocarcinoma (CCA) and to identify factors that predict mortality., Design: Retrospective study., Setting: University transplant center., Patients: Of the 132 patients with a diagnosis of CCA treated from February 1, 1985, through June 30, 2009, 75 had metastatic disease at presentation and were excluded from the study, whereas 57 patients were candidates for surgical therapy. Tumor type was intrahepatic in 37 patients and hilar in 20 patients. Surgical therapy included orthotopic liver transplant (OLT) in 38 patients and combined radical bile duct resection with partial hepatectomy (RR) in 19 patients., Results: Tumors were locally advanced in 35 of 37 patients (95%) with intrahepatic tumors and 16 of 20 patients (80%) with hilar tumors. Adjunctive therapy was used in 35 patients (61%). The 5-year tumor recurrence-free patient survival was significantly higher in the OLT group compared with the RR group (33% vs 0%; P = .05). In the OLT group, neoadjuvant and adjuvant therapies resulted in better patient survival compared with no therapy or adjuvant therapy only (47% vs 20% vs 33%, respectively; P = .03). Multivariate factors predictive of worse survival outcomes included hilar CCA, multifocal tumors, perineural invasion, and RR as the treatment modality compared with OLT. Tumor sizes--5 cm or larger for intrahepatic and 3 cm or larger for hilar CCA--were not predictors of poor outcome., Conclusion: Orthotopic liver transplant in combination with neoadjuvant and adjuvant therapies is superior to RR with adjuvant therapy in locally advanced intrahepatic and hilar CCA.

Background: Current criteria for orthotopic liver transplantation (OLT) for cholangiocarcinoma (CCA) remain restricted to early stage and small hilar tumors, excluding patients with locally advanced intrahepatic and hilar CCA for potential cure. The present study was undertaken to define a prognostic scoring system for risk stratification of patients with intrahepatic and hilar CCA who might benefit from OLT and to allow expansion of current OLT criteria., Study Design: We conducted a retrospective review of 40 patients who underwent OLT for locally advanced intrahepatic and hilar CCA at our center between February 1985 and June 2010. Median follow-up was 3 years. Independent risk factors for tumor recurrence after OLT were identified using the Cox model and were assigned risk score points. Points were summed and assigned to predictive index categories: 0 to 3 for low risk, 4 to 7 for intermediate risk, and 8 to 15 for high risk., Results: Seven multivariate factors predictive for tumor recurrence included multifocal tumor, perineural invasion, infiltrative growth pattern, lack of neoadjuvant and adjuvant therapy, history of primary sclerosing cholangitis, hilar tumors, and lymphovascular invasion. The 5-year tumor recurrence-free patient survival was significantly higher in low-risk (78%) compared with intermediate- (19%) and high-risk (0%) groups (p < 0.001); survival benefit was also seen in intermediate- compared with high-risk groups., Conclusions: This model was highly predictive of long-term outcomes after OLT for locally advanced intrahepatic and hilar CCA and can be applied clinically for risk stratification of patients considered for OLT. Long-term disease recurrence-free survival was excellent in low-risk and acceptable in intermediate-risk groups, justifying the expansion of liver transplant criteria for treatment of this challenging malignancy., (Copyright © 2011. Published by Elsevier Inc.)

Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, is notoriously difficult to diagnose, and is associated with a high mortality. Surgical resection is the only chance for cure or long-term survival. The treatment of CCA has remained challenging because of the lack of effective adjuvant therapy, aggressive nature of the disease, and critical location of the tumor in close proximity to vital structures such as the hepatic artery and the portal vein. Moreover, the operative approach is dictated by the location of the tumor and the presence of underlying liver disease. During the past 4 decades, the operative management of CCA has evolved from a treatment modality that primarily aimed at palliation to curative intent with an aggressive surgical approach to R0 resection and total hepatectomy followed by orthotopic liver transplantation.

Background: New strategies have been developed to expand indications for liver surgery. The objective was to evaluate the current practice worldwide regarding critical liver mass and manipulation of the liver volume., Methods: A survey was sent to 133 liver centers worldwide, which focused on (a) critical liver volume, (b) preoperative manipulation of the liver mass, and (c) use of liver biopsy and metabolic tests., Results: The overall response rate to the survey was 75%. Half of the centers performed more than 100 resections per year; 86% had an associated liver transplant program. The minimal remnant liver volume for resection was 25% (15-40%) in cases of normal liver parenchyma and 50% (25-90%) in the presence of underlying cirrhosis. The minimal remnant liver volume for living donors was 40% (30-50%), whereas the accepted graft body weight ratio was 0.8 (0.6-1.2). Portal vein occlusion to manipulate the liver volume before resection was performed in 89% of the centers., Conclusions: Limits of liver volume and the current practice of liver manipulation before resection were comparable among different centers and continents. The minimal remnant liver volume in normal liver was 25%, and more than 80% of the centers performed portal vein occlusion.

The growing discrepancy between the need and the availability of donor livers has resulted in evolving surgical approaches in liver transplantation during the last two decades to expand the donor pool. One approach is to transplant partial grafts, obtained either from a living donor or splitting a cadaveric donor liver. For both surgical methods, it is important to obtain a minimal viable graft volume to prevent small-for-size syndrome and graft failure. This minimal volume, expressed as graft-to-whole body ratio, must be between 0.8 and 1%. Living donor liver transplantation (LDLT) became the primary transplant option in many Asian countries and is increasingly performed as an adjunct transplant option in countries with low donation rates. Split liver transplantation (SLT) is a surgical method that creates two allografts from one deceased donor. The most widely used splitting technique is the division of the liver into a left lateral sectoral graft (segments 2 and 3) for a pediatric patient and a right trisegmental graft (segments 1 and 4 to 8) for an adult patient. Both LDLT and SLT are also important and established methods for the treatment of pediatric patients. Another evolving surgical approach is auxiliary liver transplantation, which describes the transplanting a whole or partial graft with preservation of the partial native liver. This bridging technique is applied in patients with fulminate liver failure and should allow the regeneration of the injured liver with the potential to discontinue immunosuppression. Other methods such as xenotransplantation, as well as hepatocyte and stem cell transplantation, are promising approaches that are still in experimental phases.

Here we report the first adult patient who survived severe adenoviral hepatitis of a liver graft, in contrast to 4 previously reported cases in adults, all of which had a fatal outcome. Early diagnosis was based on the immunohistological detection of adenoviral protein in the context of biopsy-proven hepatitis. Dramatic reduction of immunosuppression along with supportive care were the treatment strategies in this case. Adenoviral infection of the allograft should always be considered as a differential diagnosis when clinical signs of severe hepatitis are present after liver transplantation. Accurate diagnosis with immunohistochemical detection of viral proteins in the liver graft is of paramount importance for the early diagnosis and management of this uncommon, severe, and probably underdiagnosed entity.

Background: Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers., Methods: We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers., Results: During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%-100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (> or =21 days) and hospital (> or =40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient., Conclusion: Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.

Post-transplant lymphoproliferative disease (PTLD) is a serious and potentially life-threatening complication after solid organ transplantation. Here, we report our first experience with the use of PET/CT (positron emission tomography combined with computed tomogram) for the management of patients with PTLD after liver transplantation. Four patients with histologically proven PTLD were analyzed. Conventional work-up included physical examination and head-to-pelvis CT. PET/CT was used in one patient for initial staging and in all patients for follow-up. PET/CT positive findings underwent biopsy. Information provided by PET/CT resulted in a change of medical management in three of the four patients. Conventional work-up missed residual disease after surgery in one and failed to detect a tumor relapse in another patient. However, one patient disclosed a false positive PET/CT finding in the lungs. In conclusion, PET/CT may be a useful tool for staging and therapy monitoring of PTLD after liver transplantation.

Background: Although graft-resident passenger leukocytes are known to mediate acute rejection by triggering direct allorecognition, they may also act in an immunomodulatory fashion and play an important role in tolerance induction. Our purpose in the current study was to utilize rat bone marrow chimeras to evaluate the role of the genotype of passenger leukocytes in both acute rejection and tolerance of liver allografts., Methods: The fate of livers bearing donor-type, recipient-type, and third-party passenger leukocytes was evaluated in the MHC class I and II mismatched rejector combination ACI-->LEW and the acceptor combination PVG-->DA., Results: We report that although treatment of ACI liver donors with lethal irradiation does not lead to prolongation of graft survival in the ACI-->LEW strain combination, ACI livers bearing recipient-type (LEW) or third-party passenger leukocytes (BN) are rejected at a significantly slower rate. We confirm that lethal irradiation of PVG donor animals leads to abrogation of tolerance induction with acute rejection of their livers by DA recipients. However, the majority of PVG livers carrying donor-type (PVG), recipient-type (DA), or third-party (LEW) passenger leukocytes are accepted for >100 days. These DA recipients develop immune tolerance to the donor parenchyma (PVG)., Conclusions: Our findings demonstrate that long-term acceptance of liver allografts and tolerance induction is not dependent on the presence of donor-type passenger leukocytes and can be achieved with organs carrying donor-type, recipient-type, or third-party passenger leukocytes. The importance of the MHC framework on the surface of passenger leukocytes as a critical regulator of the immune response after transplantation of chimeric organs is substantiated by the delayed tempo of rejection of ACI livers bearing recipient-type or third-party passenger leukocytes in the ACI-->LEW strain combination.

Idiopathic portal hypertension (IPH) was diagnosed in a 30-year-old man. Clinical signs were splenomegaly, leucothrombocytopenia, and esophageal varices of fourth degree. The histology of the liver biopsy showed portal fibrosis with no evidence of cirrhosis. No causing agent or known disease could be found for the histopathological and clinical features. Due to a severe deterioration of general condition and a decline of synthetic liver function, liver transplantation and splenectomy were performed. The histological examination of the explanted liver revealed features of IPH, demonstrating portal fibrosis and dilated vessels adjacent to portal tracts; no cirrhosis was found. The postoperative recovery was without any severe complications. The duration of hospitalization was 28 days. Following liver transplantation, the esophageal varices disappeared and leucocytes, platelets as well as parameters of hepatic synthesis reached normal values. Initially, the immunosuppression was composed of prednisolon, tacrolimus, and antibodies against IL-2 receptors (BT 563) and was later continued with prednisolon and tacrolimus. Within the follow-up observation of 26 months, there was no evidence for graft rejection, severe infection, or occurrence of portal hypertension. Up till now the patient is in good condition with normal graft function. Liver transplantation may be a curative therapy for patients with advanced disease of IPH but the long-term follow-up after transplantation has to show whether IPH can reoccur.

For experimental liver transplantation in the rat, the models that have been used most frequently do not include reconstruction of the arterial blood supply to the liver. In these procedures, specially developed cuff anastomoses rather than the conventional microvascular suture technique are used almost exclusively in the recipient operation, so that the anhepatic time is minimized. In this study the technical details of an improved rat model for orthotopic liver transplantation are described. During the donor operation in this experimental method, the liver is prepared with an arterial pedicle that includes the abdominal segment of the aorta, permitting perfusion in situ of the portal vein as well as the hepatic artery. The transplantation of the excised donor organ into the recipient site is carried out with simplified microvascular suture techniques and includes reconstruction of the arterial supply to the liver. Anastomosis of the bile duct is accomplished by choledocho-choledochostomy with a splint technique and supplemental suturing. For the entire procedure, magnifying glasses with 2- to 2.5-fold magnification are sufficient. When this technique has been mastered, the average duration of the anhepatic phase is about 20 min, well below the critical 30-min limit for survival of the experimental animals. As proficiency increased, the perioperative mortality was reduced to 9.2% (n = 130). With the combination of portal and arterial in situ flushing during the donor operation and the rearterialization of the transplant during the recipient operation, the clinical conditions can be approximated more closely than is possible when the transplanted rat liver is supplied only by the portal vein. Use of microvascular suture techniques, without cuff anastomoses, reduces the need for ex situ handling of the donor organ.

The methods for liver transplantation in the rat mainly used do not include reconstruction of the arterial blood supply to the liver. Furthermore, to ensure a short anhepatic phase these methods almost all entail specially developed cuff anastomoses in the recipient operation instead of the conventional microvascular suture technique. Thus an acceptable survival rate can be attained in the experimental animals. This detailed description of simplified microvascular suture techniques is intended to present an alternative to the cuff anastomoses used almost exclusively. In the donor operation with this method, the liver is dissected with an arterial pedicle including the abdominal segment of the aorta, and the liver is flushed in situ not only via the portal vein, but also via the hepatic artery. The organ is implanted in the recipient animal using simplified microvascular suture reconstruction of the arterial blood supply to the liver. Use of telescopic spectacles with 2-fold magnification has proven to be adequate for the entire procedure. With mastery of this method of rat liver transplantation, the average duration of the anhepatic phase is about 20 min, substantially below the 30-min limit which is critical for the survival of the experimental animals. The donor operation requires about 60 min, and the recipient operation 70 to 80 min. With this method, the spectrum of investigations on liver transplantation which are possible in the rat is substantially extended in that clinical conditions can be reproduced very much more exactly by combination of portal and arterial in-situ flushing in the donor operation and rearterialization of the transplant in the recipient operation, as compared to the transplanted rat liver being supplied only with portal venous blood.

Background: Enterothorax (ET) is a rare complication after hepatic surgery. The literature in this field is limited and mainly based on case reports. The aim of this study was to review our department's experience.Patients and methods: We retrospectively analyzed 602 patients who underwent hepatic resection between November 2008 and December 2016. Major hepatic surgery (n = 321) was defined as right or extended right hepatectomy (n = 227), left or extended left hepatectomy (n = 63), trisegmentectomy (n = 13), and living donor liver transplantation (n = 18). ET cases were identified by analyzing clinical courses and radiological imaging.Results: ET was observed in five out of 602 patients (0.8%). All patients developed the complication after major hepatic surgery (five out of 321, 1.6%). ET exclusively occurred after right (n = 3) or extended right hepatectomy (n = 2). Median time to diagnosis was 22 months. Radiological imaging showed herniation of small (n = 2), large bowel (n = 2), or omental fat (n = 1) with a median diaphragmatic defect of 3.9 cm. Two patients presented with acute incarceration and underwent emergency surgery, one patient reported recurrent pain and underwent elective repair, and two patients refused surgery. Follow-up imaging in two operated patients showed no recurrence of ET after 36 and 8 months.Conclusions: Patients after right hepatectomy have a substantial risk of ET. Acute right upper quadrant pain and/or dyspnea after hepatectomy should be investigated with adequate radiological imaging. Elective surgical repair of ET is recommended to avoid emergency surgery in case of incarceration. [ABSTRACT FROM AUTHOR]