The preoperative recurrence score: Predicting early recurrence in peri-hilar cholangiocarcinoma.

INTRODUCTION: Despite advances in surgical techniques, the rate of early recurrence in perihilar cholangiocarcinoma (PCC) remains high. We sought to develop the Preoperative Recurrence Score (PRS), a model to estimate the risk of early recurrence after resection based on preoperative radiological characteristics. MATERIALS AND METHODS: Data of patients who underwent surgery for PCC were retrospectively collected, and preoperative imaging was reviewed to assess tumor characteristics. A model to assess the risk of early recurrence based on preoperative radiologic characteristics was internally developed and externally validated on two cohorts of patients from two European major hepatobiliary surgery referral centers. RESULTS: A total of 215 patients among three different patient cohorts were included in the study. Tumor size ≥18 mm (HR 2.70, 95 % CI 1.48-4.92, p = 0.001), macroscopic portal vein involvement (HR 2.28, 95%CI 1.19-4.34, p = 0.013), hepatic arteries involvement (HR 2.44, 95%CI 1.26-4.71, p = 0.008), and presence of suspicious lymph nodes (HR 1.98, 95%CI 1.02-3.83, p = 0.043) were significantly associated with recurrence-free survival (RFS). The model showed excellent discrimination both on the internal (AUC 0.83) and external validation cohorts (external 1: AUC 0.84; external 2: AUC 0.70). High PRS was associated with worse RFS among all three cohorts, with a 1-year recurrence probability of 80.1 %, 100.0 %, and 54.2 % in the internal and external validation cohorts 1 and 2, respectively. CONCLUSIONS: The PRS is a simple tool that can accurately assess the risk of early recurrence in patients with PCC. Up-front surgery should be carefully evaluated in patients with high PRS, as it could result in a futile resection.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation.

Purpose: In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. Methods: aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. Results: The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301-451) µg/kg/h versus those who did not 105 (70-158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = - 0.755) and aspartate transaminase (AST; R = - 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346-453) µg/kg/h) from those who were discarded (155 (87-206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. Conclusions: This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00371-7.

Core outcome sets and benchmarking complications: Defining best practices for standardized outcome reporting in liver transplantation.

The comparison of outcomes in liver transplantation (LT) is hampered by using clinically non-relevant surrogate endpoints and considerable variability in reported relevant post-transplant outcomes. Such variability stems from non-standard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is non-specific to an intervention and there are unsolved dilemmas specifically related to liver transplantation. Core Outcome Sets (COS) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the five major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time-points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index (CCI®). The Clavien scale and CCI® are specifically reviewed to enhance their utility in LT, and their use along with the COS is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system & CCI® to improve reproducibility and generalizability of research concerning liver transplantation.

Kidney Transplant Outcome Following Donation After Euthanasia.

Importance: In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool. Objectives: To investigate the outcomes of DCD-V kidney transplantation and compare them with outcomes of kidney transplantation after circulatory death after withdrawal of life-sustaining therapies (DCD type III [DCD-III]) and donation after brain death (DBD). Design, Setting, and Participants: A retrospective cohort study was conducted using the database from the Dutch Transplant Foundation. All kidney transplants in the Netherlands between January 2012 (start of the euthanasia program) and July 2023 were included. Follow-up was obtained through 5 years after transplantation. Data analysis was performed from November 2023 until February 2024. Exposures: Kidney transplantation with a DCD-V graft compared with DCD-III and DBD grafts. Main Outcomes and Measures: The primary outcome was death-censored graft survival until 5 years after transplantation. Secondary outcomes were the incidence of delayed graft function (DGF), permanent nonfunction (PNF), serum creatinine concentration, and patient survival until 5 years after kidney transplantation. Results: A total of 145 DCD-V kidney transplants were compared with 1936 DCD-III and 1255 DBD kidney transplants. Median (IQR) recipient age was 59 (46-66) years in the DCD-V cohort, compared with 61 (50-68) years in the DCD-III cohort and 61 (50-68) years in the DBD cohort. The incidence of DGF with DCD-V kidney transplants (26%) was significantly less than that with DCD-III kidney transplants (49%; P < .001) and similar to that with DBD kidney transplants (22%; P = .46). PNF occurrence with DCD-V kidneys (6%) was similar to that with DCD-III kidneys (6%; P = .79) and higher than in DBD kidneys (4%; P < .001). There was no difference in 5-year death-censored graft survival between DCD-V grafts (82%) and DCD-III (86%; P = .99) or DBD (84%; P = .99) grafts. There was no difference in 5-year patient survival between DCD-V kidney transplants (69%) and DCD-III (76%; P = .45) or DBD (73%; P = .74) kidney transplants. A propensity score analysis was performed to match the DCD-V and DCD-III cohort, showing results similar to those of the unmatched cohort. Conclusions and Relevance: This study found that DCD-V kidney transplantation yielded a lower incidence of DGF compared with DCD-III kidney transplantation and yielded long-term results similar to those of DCD-III and DBD kidney transplantation. The findings suggest that DCD-V is a safe and valuable way to increase the kidney donor pool.

Endoscopic ultrasound with tissue acquisition of lymph nodes in patients with potentially resectable intrahepatic cholangiocarcinoma.

Background and study aims Lymph node (LN) involvement is a poor prognostic factor for patients with intrahepatic cholangiocarcinoma (iCCA). The aim of this study was to evaluate the yield and impact on clinical decision making of endoscopic ultrasound with tissue acquisition (EUS-TA) of LNs in patients with potentially resectable iCCA. Patients and methods In this multicenter cohort study, patients with potentially resectable iCCA and preoperative EUS between 2010 and 2020 were retrospectively included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to pathologically confirmed positive LNs found with EUS-TA. Results A total of 56 patients underwent EUS, with 91% of patients to target suspicious LNs on imaging. EUS-TA of LNs confirmed malignancy in 21 LNs among 19 patients (34%). In 17 patients (30%), surgical exploration was withheld due to nodal involvement. Finally, 24 patients (43%) underwent surgical exploration among whom positive regional LNs were identified in six patients (25%). Conclusions In patients with potentially resectable iCCA and suspicious LNs on cross-sectional imaging, EUS-TA confirmed LN involvement in 30% of patients. Surgical exploration was withheld mostly because of extraregional LN involvement and regional LN involvement in patients with high surgical risk.

Graft Steatosis and Donor Diabetes Mellitus Additively Impact on Recipient Outcomes After Liver Transplantation-A European Registry Study.

BACKGROUND AND AIMS: Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. METHODS: We analyzed data from all consecutive first adult full-graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation-free survival were studied through survival analyses. RESULTS: Of 12 174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p < 0.001) and donor DM (aHR 1.157, p = 0.004) were independently associated with impaired retransplantation-free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p = 0.0185]; steatosis alone, aHR: 1.200 [p < 0.001]; both steatosis and DM, aHR: 1.381 [p < 0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation-free survival within 7 days. CONCLUSIONS: Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high-risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation.

Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Benefits and barriers to accreditation of HPB center and fellowship programs in Europe: a strength-weakness-opportunity-and-threats (SWOT) analysis by an E-AHPBA-ESSO-UEMS ad hoc working committee.

BACKGROUND: Training in HPB surgery lacks uniformity across regions covered by the E-AHPBA. Accreditation has been in place for centers and fellowship programs, but with low uptake. The decision whether to continue, change or cease such accreditation is being discussed. Thus, a strengths, weaknesses, opportunities, and threats (SWOT) analysis was conducted. METHODS: A mixed-methods, cross-sectional study among stakeholders in E-AHPBA, ESSO and UEMS under the E-AHPBA executive council was founded, ensuring representation by gender and geographic distribution. RESULTS: Responses were collected from across E-AHPBA regions, with response from 15 of 24 subchapters. The most frequent and recurring themes are presented in a SWOT matrix which allows for paired evaluations of factors deemed to be helpful (Strengths and Opportunities), those that are harmful (Weaknesses and Threats). CONCLUSION: This study identified both helpful and harmful effects to an accreditation process of HPB centers or HPB fellowship training across the E-AHPBA membership region. Formal accreditation of centers is not within the scope, nor jurisdiction nor financial capacity for E-AHPBA in the current situation. A strong interest in formal HPB training should be capitalized into E-AHPBA strategic planning towards a structured accreditation system for HPB fellowship programs or HPB training tracks.

Risks of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Liver Transplantation.

Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post-ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty-two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher.

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis - an ELTR study.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9-17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p <0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p <0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p <0.001, and aHR 1.34, 95% CI 1.15-1.56, p <0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low. Impact and implications: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Older living liver donors can enlarge the donor pool: a systematic review and meta-analysis.

BACKGROUND: Living donor liver transplantation (LDLT) is the best option for end-stage liver disease patients. Older potential donors are increasingly requesting donation. This study aims to systematically assess the differences in donor perioperative and postoperative complications, mortality, and quality of life (QoL) between younger and older living liver donors. MATERIALS AND METHODS: Embase, Medline, and Cochrane were searched for studies published between 2002 and 2 June 2023. Donor complications, major complications, biliary complications, mortality, and QoL were systematically reviewed, including meta-analyses. Donors aged >50 years were considered older. The methodological quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale. RESULTS: The search yielded 8320 studies, of which 17 were included. The risk ratio (RR) for complications in younger donors was 1.08 [0.90-1.31] ( P =0.41). RRs for major complications in younger donors were 0.98 [0.64, 1.48] and 0.89 [0.50, 1.57] using Clavien-Dindo ≥III and ≥IIIb as major complication. RR for biliary complications in younger donors was 1.59 [1.05-2.42] ( P =0.03). Mortality rate in younger donors was 47/13 238 (0.4%) and in older donors 13/989 (1.3%). Physical component summary (PCS) in younger donors was 51.87 and in older donors 51.29. Mental component summary (MCS) in younger donors was 52.93 and in older donors 55.40. CONCLUSION: Older donors do not have a higher complication or mortality rate than younger donors after LDLT. They may have a lower rate of biliary complications. Additionally, older donors have a similar QoL after LDLT. With careful selection, older donors can be included in screening programs for living liver donation to expand the donor pool.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

The Yield of Routine Post-Operative Doppler Ultrasound to Detect Early Post-Liver Transplantation Vascular Complications.

Early detection of liver transplantation (LT) vascular complications enables timely management. Our aim was to assess if routine Doppler ultrasound (rDUS) improves the detection of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT) and hepatic venous outflow obstruction (HVOO). We retrospectively analysed timing and outcomes, number needed to diagnose one complication (NND) and positive predictive value (PPV) of rDUS on post-operative day (POD) 0,1 and 7 in 708 adult patients who underwent primary LT between 2010-2022. We showed that HAT developed in 7.1%, PVT in 8.2% and HVOO in 3.1% of patients. Most early complications were diagnosed on POD 0 (26.9%), 1 (17.3%) and 5 (17.3%). rDUS correctly detected 21 out of 26 vascular events during the protocol days. PPV of rDUS was 53.8%, detection rate 1.1% and NND was 90.5. Median time to diagnosis was 4 days for HAT and 47 days for PVT and 21 days for HVOO. After intervention, liver grafts were preserved in 57.1%. In conclusion, rDUS protocol helps to detect first week's vascular events, but with low PPV and a high number of ultrasounds needed.

Development of a model to predict the risk of early graft failure after adult-to-adult living donor liver transplantation: An ELTR study.

Graft survival is a critical end point in adult-to-adult living donor liver transplantation (ALDLT), where graft procurement endangers the lives of healthy individuals. Therefore, ALDLT must be responsibly performed in the perspective of a positive harm-to-benefit ratio. This study aimed to develop a risk prediction model for early (3 months) graft failure (EGF) following ALDLT. Donor and recipient factors associated with EGF in ALDLT were studied using data from the European Liver Transplant Registry. An artificial neural network classification algorithm was trained on a set of 2073 ALDLTs, validated using cross-validation, tested on an independent random-split sample (n=518), and externally validated on United Network for Organ Sharing Standard Transplant Analysis and Research data. Model performance was assessed using the AUC, calibration plots, and decision curve analysis. Graft type, graft weight, level of hospitalization, and the severity of liver disease were associated with EGF. The model ( http://ldlt.shinyapps.io/eltr_app ) presented AUC values at cross-validation, in the independent test set, and at external validation of 0.69, 0.70, and 0.68, respectively. Model calibration was fair. The decision curve analysis indicated a positive net benefit of the model, with an estimated net reduction of 5-15 EGF per 100 ALDLTs. Estimated risks>40% and<5% had a specificity of 0.96 and sensitivity of 0.99 in predicting and excluding EGF, respectively. The model also stratified long-term graft survival ( p <0.001), which ranged from 87% in the low-risk group to 60% in the high-risk group. In conclusion, based on a panel of donor and recipient variables, an artificial neural network can contribute to decision-making in ALDLT by predicting EGF risk.

Quantifying the Disadvantage of Small Recipient Size on the Liver Transplantation Waitlist, a Longitudinal Analysis Within the Eurotransplant Region.

BACKGROUND: Small adult patients with end-stage liver disease waitlisted for liver transplantation may face a shortage of size-matched liver grafts. This may result in longer waiting times, increased waitlist removal, and waitlist mortality. This study aims to assess access to transplantation in transplant candidates with below-average bodyweight throughout the Eurotransplant region. METHODS: Patients above 16 y of age listed for liver transplantation between 2010 and 2015 within the Eurotransplant region were eligible for inclusion. The effect of bodyweight on chances of receiving a liver graft was studied in a Cox model corrected for lab-Model for End-stage Liver Disease (MELD) score updates fitted as time-dependent variable, blood type, listing for malignant disease, and age. A natural spline with 3 degrees of freedom was used for bodyweight and lab-MELD score to correct for nonlinear effects. RESULTS: At the end of follow-up, the percentage of transplanted, delisted, and deceased waitlisted patients was 49.1%, 17.9%, and 24.3% for patients with a bodyweight <60 kg (n = 1267) versus 60.1%, 15.1%, and 18.6% for patients with a bodyweight ≥60 kg (n = 10 520). To reach comparable chances for transplantation, 60-kg and 50-kg transplant candidates are estimated to need, respectively, up to 2.8 and 4.0 more lab-MELD points than 80-kg transplant candidates. CONCLUSIONS: Decreasing bodyweight was significantly associated with decreased chances to receive a liver graft. This resulted in substantially longer waiting times, higher delisting rates, and higher waitlist mortality for patients with a bodyweight <60 kg.

Primary sclerosing cholangitis and other risk factors for post-transplant lymphoproliferative disease after liver transplantation in adults.

Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD after LT in adults. All adult LT recipients between 1986 and 2016 from 2 centers in the Netherlands were included, with follow-up until 2020. PTLD was diagnosed according to the World Health Organization (WHO) classification. Potential risk factors for PTLD were assessed using multivariate Cox regression analysis. A total of 1281 patients were included, of whom 29 (2.3%) developed PTLD. Results show that independent risk factors for PTLD after LT in adults were no Epstein-Barr virus load monitoring strategy, primary sclerosing cholangitis as an indication for LT, era (historic era linked to more intense long-term immunosuppression), and Epstein-Barr virus-seronegative recipient. No other independent risk factors were identified in this study. Of the 207 patients with primary sclerosing cholangitis as an indication for LT, 13 (6.3%) developed PTLD versus 16 out of 1074 (1.5%) patients with other underlying liver diseases (log-rank p <0.001). The yearly PTLD incidence was higher in the first year than in the later years after LT (2.4%/y vs. 0.6%/y) for primary sclerosing cholangitis, but not for other indications (0.16%/y). In Epstein-Barr virus-seronegative recipients PTLD occurred earlier after LT, while in 97% of seropositive recipients it could occur very late after LT.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.