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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

IntroductionThis systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and oncological safety before major hepatectomy.MethodsWe conducted this systematic review and meta-analysis following the PRISMA guidelines 2020 and AMSTAR 2 guidelines. Comparative articles published before November 2022 were retained.ResultsThe literature search identified nine eligible comparative studies. They included 557 patients, 207 in the LVD group and 350 in the PVE group. This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, percentage of FLR hypertrophy, lower failure of resection due to low FLR, faster kinetic growth, higher day 5 prothrombin time, and higher 3 years’ disease-free survival. This study did not find any difference between the LVD and PVE groups in terms of complications related to embolization, FLR percentage of hypertrophy after embolization, failure of resection, 3-month mortality, overall morbidity, major complications, operative time, blood loss, bile leak, ascites, post hepatectomy liver failure, day 5 bilirubin level, hospital stay, and three years’ overall survival.ConclusionLVD is as feasible and safe as PVE with encouraging results making some selected patients more suitable for surgery, even with a small FLR.Systematic review registrationThe review protocol was registered in PROSPERO before conducting the study (CRD42021287628).

Abstract Background Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia–reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. Methods HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. Discussion We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing. Trial registration ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.

Background:. Laparoscopic donor right hepatectomy (LDRH) is a technically challenging procedure. There is increasing evidence demonstrating the safety of LDRH in high-volume expert centers. We report our center’s experience in implementing an LDRH program in a small- to medium-sized transplantation program. Methods:. Our center systematically introduced a laparoscopic hepatectomy program in 2006. We started with minor wedge resections followed by major hepatectomies with increasing complexities. In 2017, we performed our first laparoscopic living donor left lateral sectionectomy. Since 2018, we have performed 8 cases of right lobe living donor hepatectomy (laparoscopy-assisted: 4 and pure laparoscopic: 4). Results:. The median operative time was 418 (298–540) min, whereas the median blood loss was 300 (150–900) mL. Two patients (25%) had surgical drain placed intraoperatively. The median length of stay was 5 (3–8) d, and the median time to return to work was 55 (24–90) d. None of the donors sustained any long-term morbidity or mortality. Conclusions:. Small- to medium-sized transplant programs face unique challenges in adopting LDRH. Progressive introduction of complex laparoscopic surgery, a mature living donor liver transplantation program, appropriate patient selection, and the invitation of an expert to proctor the LDRH are necessary to ensure success.

Background & Aims: Biliary complications (BC) following liver transplantation (LT) are responsible for significant morbidity. No technical procedure during reconstruction has been associated with a risk reduction of BC. The placement of an intraductal removable stent (IRS) during reconstruction followed by its endoscopic removal showed feasibility and safety in a preliminary study. This multicentric randomised controlled trial aimed at evaluating the impact of an IRS on BC following LT. Methods: This multicentric randomised controlled trial was conducted in 7 centres from April 2015 to February 2019. Randomisation was done during LT when a duct-to-duct anastomosis was confirmed with at least 1 of the stump diameters ≤7 mm. In the IRS group, a custom-made segment of a T-tube was placed into the bile duct to act as a stake during healing and was removed endoscopically 4 to 6 months post LT. The primary endpoint was the incidence of BC (fistulae and strictures) within 6 months post LT. The secondary criteria were complications related to the IRS placement or extraction, including endoscopic retrograde cholangio-pancreatography (ERCP)-related complications. Results: In total, 235 patients were randomised: 117 in the IRS group and 118 in the control group. BC occurred in 31 patients (26.5%) in the IRS group vs. 24 (20.3%) in the control group (p = 0.27), including 16 (13.8%) and 15 (12.8%) strictures, respectively. IRS migration occurred in 24 patients (20.5%), cholangitis in 1 (0.9%), acute pancreatitis in 2 (1.8%), and difficulty during endoscopic extraction in 19 (19.4%). No predictive factor for BC was identified. Conclusions: IRS does not prevent BC after LT and may require specific endoscopic expertise for removal. Trial registration number (ClinicalTrials.gov): NCT02356939 (https://clinicaltrials.gov/ct2/show/NCT02356939?term=NCT02356939&draw=2&rank=1). Lay summary: Liver transplantation is a life-saving treatment for many patients with end-stage liver disease. However, it can be associated with complications involving the bile duct reconstruction. Herein, the placement of a specific stent called an intraductal removable stent was trialled as a way of reducing bile duct complications in patients undergoing liver transplantation. Unfortunately, it did not help preventing such complications.

Background and Objectives: Laparoscopic cholecystectomy (LC) is one of the most performed surgeries worldwide. Procedure difficulty and patient outcomes depend on several factors which are not considered in the current literature, including the learning curve, generating confusing and subjective results. This study aims to create a scoring system to calculate the learning curve of LC based on hepatobiliopancreatic (HPB) experts’ opinions during an educational course. Materials and Methods: A questionnaire was submitted to the panel of experts attending the HPB course at Research Institute against Digestive Cancer-IRCAD (Strasbourg, France) from 27–29 October 2022. Experts scored the proposed variables according to their degree of importance in the learning curve using a Likert scale from 1 (not useful) to 5 (very useful). Variables were included in the composite scoring system only if more than 75% of experts ranked its relevance in the learning curve assessment ≥4. A positive or negative value was assigned to each variable based on its effect on the learning curve. Results: Fifteen experts from six different countries attended the IRCAD HPB course and filled out the questionnaire. Ten variables were finally included in the learning curve scoring system (i.e., patient body weight/BMI, patient previous open surgery, emergency setting, increased inflammatory levels, presence of anatomical bile duct variation(s), and appropriate critical view of safety (CVS) identification), which were all assigned positive values. Minor or major intraoperative injuries to the biliary tract, development of postoperative complications related to biliary injuries, and mortality were assigned negative values. Conclusions: This is the first scoring system on the learning curve of LC based on variables selected through the experts’ opinions. Although the score needs to be validated through future studies, it could be a useful tool to assess its efficacy within educational programs and surgical courses.

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23–1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99–1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21–3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31–2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.

Background & Aims: Malignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC). Methods: This single-centre retrospective study included all patients who underwent LR for MT-HCA at Beaujon Hospital between 2001 and 2019. MT-HCAs were classified as small foci of malignant transformation HCA (SF-HCA) and as malignant HCA (M-HCA) in cases of predominant HCC foci. Recurrence-free survival (RFS) of MT-HCA was compared with that of NP-HCC after propensity score matching. Results: Forty patients (24 men, 16 women) underwent LR for MT-HCA, including 23 with SF-HCA and 17 with M-HCA. Of these cases, 16/40 (40%) had β-catenin mutations, 19/40 (47.5%) were inflammatory, 1 was HNF1α-mutated HCA and 4 (10%) were unclassified HCA. Microvascular invasion (12% vs. 0%, p = 0.091) and satellite nodules (25% vs. 4%, p = 0.028) were more frequently observed in M-HCA than in SF-HCA. After a median follow-up of 67 months, 10 (25%) patients with MT-HCA had tumour recurrence, including 9 with M-HCA and 1 with SF-HCA (p = 0.007). M-HCA was linked to significantly poorer 1-, 3-, 5- and 10-year RFS rates than SF-HCA (76%, 63%, 39%, 37% vs. 100%, 100%, 100%, 91%, p = 0.003). Multivariate analysis showed that SF-HCA was independently associated with improved RFS (hazard ratio 0.064; 95% CI 0.008–0.519; p = 0.01). After propensity score matching, NP-HCC was associated with significantly poorer 1-, 3-, 5- and 10-year RFS rates than MT-HCA (p = 0.01). Conclusions: HCA with malignant transformation yields a better long-term prognosis than NP-HCC. Among MT-HCA, SF-HCA is associated with a better prognosis than M-HCA. Lay summary: The prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival.

Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.

Background: To evaluate the cost-effectiveness of the extended use of ablation for the treatment of hepatocellular carcinoma (HCC) with cirrhosis in an expert ablation center when compared to the non-extended use of ablation in equivalent tertiary care centers. Methods: Consecutive cirrhotic patients with non-metastatic HCC, no prior treatment, and referred to three tertiary care centers between 2012 and 2016 were retrospectively identified. The Bondy group, including all of the patients treated at Jean Verdier Hospital, where the extended use of ablation is routinely performed, was compared to the standard of care (SOC) group, including all of the patients treated at the Beaujon and Mondor Hospitals, using propensity score matching. A cost-effectiveness analysis was carried out from the perspective of French health insurance using a Markov model on a lifetime horizon. Results: 532 patients were matched. The Bondy group led to incremental discounted lifetime effects of 0.8 life-years gained (LYG) (95% confidence interval: 0.4, 1.3) and a decrease in lifetime costs of EUR 7288 (USD 8016) (95% confidence interval: EUR 5730 [USD 6303], EUR 10,620 [USD 11,682]) per patient, compared with the SOC group, resulting in a dominant mean incremental cost-effectiveness ratio (ICER). A compliance with the Barcelona Clinic Liver Classification (BCLC) guidelines for earlier stage contributed to the greater part of the ICER. Conclusion: The extended use of ablation in cirrhotic patients with HCC was more effective and less expensive than the non-extended use of the ablation strategy.

Summary: Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.

Background & Aims: The quality of surgical care of patients with HCC is associated with improved long-term prognosis and may also be influenced by the type of surgical approach. The present study aimed at evaluating the role of the laparoscopic approach on quality of surgical care and long-term prognosis in optimal HCC surgical candidates. Methods: All consecutive patients undergoing open (OLR) or laparoscopic liver resection (LLR) for early-stage HCC in cirrhosis (METAVIR F4) at 5 French expert hepato-pancreatico-biliary centres between 2010 and 2018 were enrolled. Quality of surgical care was defined by textbook outcome (TO), a combination of 6 criteria representing ideal hospitalisation. Factors associated with TO were determined on multivariate analysis. Comparison between LLR and OLR was performed after propensity score matching (PSM). The primary endpoint was disease-free survival (DFS). Statistical cure was modelled using a non-mixture model. Results: Overall, 425 patients were included. Median follow-up was 42.0 months. LLR was performed in 267 (62.8%) patients. TO was achieved in 140 (32.9%) patients. LLR was independently associated with TO (odds ratio [OR] 2.81; 95% CI 1.29–6.12; p = 0.009). After PSM, LLR patients cumulated higher number of TO criteria than OLR patients (5 vs. 4; p = 0.012). The 1-, 3-, and 5-year DFS of LLR patients with and without TO were 82.3%, 64.4%, and 62.5%, and 76.9%, 51.4%, and 30.2%, respectively (p = 0.003). On multivariable Cox regression, TO was independently associated with improved DFS (hazard ratio 0.34; p = 0.001). The cure fraction of the whole population was 24.4%. Patients achieving TO had increased cure fraction than patients not achieving TO (32.6% vs. 18.1%). Conclusions: Quality of surgical care improves the prognosis of patients with early-stage HCC and is promoted by the laparoscopic approach. Lay summary: The overall quality of surgical care, as measured by TO, plays a pivotal role in the prognosis and, in particular, on the probability of statistical cure of patients with resectable early-stage HCC occurring in cirrhosis. By influencing TO, laparoscopy has an indirect impact on the probability of cure and long-term management of these patients. This study strongly supports the promising curative role of mini-invasive treatments for early-stage HCC, such as low-difficulty LLR.

Background & Aims: We compare the performance of liver surface nodularity (LSN) and liver stiffness measurements (LSM) using transient elastography (TE) for the detection of clinically significant portal hypertension (CSPH) in patients with cirrhosis and hepatocellular carcinoma (HCC). Methods: All patients with cirrhosis and HCC who underwent computed tomography, LSM and hepatic venous pressure gradient (HVPG) measurements within 30 days between 2015 and 2018 were included. The estimation of CSPH by LSN and LSM, and the LSM-spleen-size-to-platelet ratio score (LSPS) were evaluated and compared. Results: In total, 140 patients were included (109 men [78%], mean age 63 ± 9 years old), including 39 (28%) with CSPH. LSN measurements were valid in 130 patients (93%) and significantly correlated with HVPG (r = 0.68; p 75% of patients. Such a combination could be useful in centres where the HVPG measurement is unavailable. Lay summary: The diagnostic performance and feasibility of liver surface nodularity was similar to that of liver stiffness measurement (LSM) for the detection of clinically significant portal hypertension in patients with compensated cirrhosis. Thus, liver surface nodularity could be an option for the preoperative detection of clinically significant portal hypertension in patients with hepatocellular carcinoma. Combining liver surface nodularity with LSM-spleen-size-to-platelet ratio score resulted in the accurate detection of clinically significant portal hypertension in >75% of patients, thus limiting the need for HVPG measurements.

Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure’s developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first–second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, p = 0.001) and less morbidity (8.7 vs. 18.3 %, p = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.

There is an increasing awareness in the transplant community that family plays a crucial role in releasing donor organs for transplant purposes. Although in most jurisdictions the family has little legal standing, in practice organ retrieval protocols and procedures amount to giving the next-of-kin something akin to a veto over posthumous organ removal. This situation raises important ethical and legal issues that are the subject of this article.

Introduction: The prognostic role of tumor burden score (TBS) relative to pre-operative α -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined. Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low–medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low–medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low–medium TBS/high AFP had worse OS compared with individuals with low–medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.

King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.