A 67-year-old male underwent a laparoscopic left hepatectomy with hepatic pedicle lymphadenectomy and cholecystectomy for a cholangiocarcinoma located in segment 3. The left bile duct was sectioned during parenchymal transection between 10mm Hem-o-lok® clips. Postoperative course was uneventful until post-operative day (POD) 5, when a biliary fistula appeared through the surgical drain following a transient peak of bilirubin (total/conjugated = 45/38 μM) mimicking choledochal migration. Biliary MRI at POD 13 revealed a leak from the left hepatic duct. Endoscopic ultrasound at POD 24 revealed material in the common bile duct (CBD). Following sphincterotomy, Hem-o-lok® clips were extracted from the CBD, including one measuring 10 mm long. A plastic stent was placed to cover the fistula, which resolved 5 days later. This is the first description of Hem-o-lok® clip migration from the left hepatic bile duct into the CBD, resulting in postoperative biliary fistula.

OBJECTIVE:To evaluate whether the difficulty of surgery affects failure-to-rescue (FTR) after liver transplantation (LT). SUMMARY BACKGROUND DATA:Predictors of FTR include both recipient and intraoperative factors, and their identification and improvement may reduce its incidence. METHODS:This retrospective study included all first-time isolated LTs performed in six centers. A difficult LT was defined as one in which the number of blood units transfused, cold ischemia time, and duration of surgery were all at or above the median values for the study population. FTR was defined as death within 90 days after a major postoperative complication. The correlations of a difficult LT with outcomes, including FTR, were assessed. Predictors of FTR were identified. RESULTS:The study population included 1341 patients. The respective incidences of difficult LT, 90-day major complications, 90-day mortality, and FTR were 17.4%, 53.6%, 5.8%, and 10.7%. Difficult LT was correlated with worse short-term outcomes, including a high FTR rate. Being in the intensive care unit, receiving renal replacement therapy at the time of LT, and difficult LT were independent predictors of FTR. CONCLUSIONS:Mortality following a difficult LT may be correlated to FTR. Identification of modifiable predictors of FTR may help to improve the post-transplant management of these patients.

BACKGROUND:Ex situ perfusion has been shown to improve the preservation of marginal liver grafts. Normothermic conditions allow graft viability evaluation and metabolic modifications, such as drugs injection to modify lipid content. In a previous study, we demonstrated that a pharmacologic defatting cocktail with rapamycin (DFAT) significantly reduced the triglyceride content of steatotic hepatocytes in vitro. The objective of the present study was to test the defatting cocktail in discarded human livers during ex situ perfusion. METHODS:Discarded livers were perfused according to an uninterrupted cold-to-warm protocol. The defatting cocktail was injected after 30 minutes under normothermic conditions (37 °C), whereas no defatting cocktail was administered to controls. The objective of this study was to evaluate the effect of the defatting cocktail on lipid metabolism and reduction in histologic steatosis. Liver viability was evaluated using UK viability criteria. RESULTS:Twelve discarded highly marginal livers (median Donor Risk Index 2.02 [1.6-3.47], with a median macrosteatosis of 55% [10%-90%]) underwent cold-to-warm perfusion for a median of 765 minutes (450-1,320). Defatting cocktail injection was performed in 9 livers (vs 3 controls), triggering a marked increase in triglyceride into the perfusate (at 90 minutes +164% vs +23% in controls; P < .001); a reduction of triglyceride content in liver tissue with a peak effect at 30 minutes (-46.6% vs +14.8% in controls, P = .0032); an increase in the hepatic expressions of genes related to lipid export, β-oxidation, and autophagy; and a decrease in that of lipogenesis-related genes. Five livers (41.6%) reached viability criteria, including 3 (33%) in the defatting cocktail group and 2 (67%) in the control group. A 10% reduction of histologic macrosteatosis was observed in the defatting cocktail group vs 0% in controls. CONCLUSION:Continuous cold-to-warm ex situ perfusion combined with defatting cocktail injection triggers the release of triglycerides and the activation of lipid export, β-oxidation, and autophagy pathways, together with a trend toward steatosis reduction.

Hepatocellular carcinoma is one of the most frequent cancers in the world. Treatments such as immune checkpoint inhibitors or tyrosine kinase inhibitors (TKI) have some efficacy but have many adverse effects. So, more specifically targeted therapies are needed. In this study, we investigated the antitumoral effect of a tumor-penetrating and interfering peptide blocking the interaction between the proteins PP2A and SET. We analyzed the expression of phosphatase PP2A and oncoprotein SET in a group of samples from liver cancer patients with different aggressiveness scores. Expression of both proteins was found to correlate with aggressiveness of the tumor. We observed in xenograft models of hepatocellular carcinoma an antitumoral effect of iRGD-IP, a tumor-penetrating and interfering peptide blocking PP2A/SET interaction, suggesting that this peptide could be a strong candidate for development as therapeutic peptide for liver tumor treatment.

Background Combined heart-liver transplantation (CHLT) offers new possibilities for patients with no other treatment options, yet it remains a rare and complex procedure. Despite an increase in its utilisation in recent years, data remain scarce, and many aspects of the procedure are not yet fully understood, particularly the causes of its significant perioperative morbidity, such as acute kidney injury. The CARDHEPAT study presents the first description of a French regional cohort of CHLT patients. Methods A retrospective analysis of the CARDHEPAT cohort examined 30 CHLTs performed at Assistance Publique - Hôpitaux de Paris (APHP) from January 1, 2002, to January 1, 2022. The aim of this study was to highlight the impact of postoperative KDIGO3 acute kidney injury (AKI) on recipient outcomes and its evolution. Results KDIGO3 AKI was observed in 50% of cases and was associated with an excess mortality rate among patients undergoing CHLT. At Day-30 and -90, the survival rates with KDIGO3 AKI were 67% and 53%, respectively, compared to 100% and 93% in patients without (p=0.04 and p=0.03). Additionally, we found several intraoperative factors that were associated with the occurrence of postoperative KDIGO3 AKI, including durations of extracorporeal circulation and aortic clamping and level of intraoperative acidosis but also preoperative albuminemia Conclusion The incidence of KDIGO3 AKI is high after CHLT and seems to be associated with increased mortality, with results suggesting that the intraoperative phase is crucial for its occurrence.

OBJECTIVES:Liver transplantation is a complex procedure frequently requiring transfusion of blood products to manage coagulopathy and haemorrhage. This study aimed to develop machine learning models to predict the biological effects of blood product transfusions, assisting clinicians in selecting optimal therapeutic combinations. METHODS:Using data from two cohorts over 20 years from two academic hospitals, 10 supervised machine learning models were trained and validated on four biomarkers: fibrinogen, haemoglobin, prothrombin time and activated partial thromboplastin time ratio. Models were evaluated using R², root mean squared error and SD metrics, with external validation performed on the second cohort. RESULTS:The results indicated that while certain models, such as the stack model for late fibrinogen (R²=0.63) or the extra trees model for late prothrombin time (R²=0.66), demonstrated promising predictive capacity, the overall external validation performance was suboptimal. Despite the use of a large healthcare database, a rigorous statistical methodology and an academic machine learning methodology, most models showed limited generalisability (R² < 0.5). DISCUSSION:Key limitations included the small dataset size relative to machine learning requirements, lack of advanced haemostatic parameters (eg, ROtational ThromboElastoMetry (ROTEM) or Thromboelastography (TEG)) and the variability introduced by evolving surgical practices over the 20-year study period. Despite these limitations, this study provides a reproducible framework for evaluating transfusion efficacy, supported by openly shared Python code and the application of Taylor diagrams for model evaluation. CONCLUSION:While our models are unsuitable for routine clinical use, they highlight the potential of machine learning in transfusion medicine. Future work should focus on integrating larger datasets, advanced biomarkers and real-time data.

The aim of this study was to assess the efficacy of end-ischemic hypothermic oxygenated perfusion (HOPE) used before liver transplantation (LT) with extended criteria donor (ECD) organs from donation after brain death (DBD) in reducing early allograft dysfunction (EAD) compared with static cold storage (SCS). Between 2019 and 2023, 262 ECD-DBD grafts from 8 French centers were randomly assigned for LT either after SCS (control group, n = 131) or after SCS and subsequent 1-4 h single portal HOPE before implantation (HOPE group, n = 131). The primary endpoint was the incidence of EAD. HOPE resulted in a significantly lower rate of EAD (17.6% vs 30.5%, P = .01). Severe complication rate (61.5% vs 52.4%, P = .15), comprehensive complication index (49 [34-65] vs 46 [35-65], P = .78), and 90-day mortality (5.3% vs 2.3%, P = .20) did not differ significantly between the control and HOPE groups, respectively. Four patients (4.9%) in the control group and 3 patients (3.3%) in the HOPE group experienced ischemic cholangiopathy at 1 year after LT (P = .71). In older patients receiving grafts with more than 6 hours of cold ischemia, HOPE was associated with a lower severe complication rate (26% vs72%, P = .005). HOPE in ECD grafts from DBD for LT reduces EAD with little clinical impact on morbidity and survival in recipients with low model for end-stage liver disease scores. Older recipients with long cold ischemia time might benefit the most. Clinical trial number: NCT03929523.

Hypothermic oxygenated machine perfusion (HOPE) during total vascular exclusion with veno-venous bypass for major hepatic resection is a safe procedure and could help to reduce ischemia-reperfusion lesions and related complications.

BACKGROUND:Hepatic artery (HA) injury during liver procurement is a significant concern in liver transplantation (LT). This study assessed its frequency and impact in deceased donor LT (DDLT). METHODS:This was a single-center cohort study of adults who underwent DDLT from 2010 to 2019. HA injury was defined as the section or ligation of arterial branches supplying the graft. Recipients, donors' characteristics and outcomes of LTs using grafts with HA injury (group 1, n = 35) were compared to LTs using grafts without HA injury (group 2, n = 677). A propensity score matching (PSM) was applied. The primary endpoint was 90-day hepatic artery thrombosis (HAT); secondary endpoints included major biliary complications, retransplantation, patient, and graft-survival. RESULTS:HA injury occurred in 4.9% of grafts. Aberrant HA anatomy was an independent predictive factor of HA injury (OR = 8.1 [3.7-17.9], p < 0.0001). Arterial reconstruction was required in 53.8% of injured grafts, while 23% had lateral sutures and 23% required no reconstruction. Arterial ischemia time was longer in group 1 (50 min [42-67] vs. 43 min [35-56]; p = 0.007). At 90-day, HAT (2.9% vs. 0.7%; p = 0.26), major biliary complications (5.7% vs. 7.2%, p>0.99) and retransplantation rates (2.9 % vs. 1%, p = 0.33) were similar. After PSM, theses outcomes remained comparable. The 5-year patient (74.3% vs. 78.3 %, p = 0.77) and graft-survival (70.2% vs. 75.6%, p = 0.78) were also similar. CONCLUSION:HA injury during procurement was rare and did not impact mid- or long-term LT outcomes, supporting a "non-restrictive graft policy" regarding grafts with HA injury.

BACKGROUND:Roux-en-Y hepaticojejunostomy (RYHJ) is currently the standard surgical technique for reestablishing biliary continuity, but it exposes the patient to serious biliary complications, such as anastomosis stricture and ascending cholangitis. METHODS:The literature on biliary replacement using vein grafts as autologous substitutes according to the different stages of the IDEAL framework was reviewed. RESULTS:Innovative biliary replacement techniques using bile duct substitutes have yet to reach stage 2a (development) of the IDEAL framework. Vein grafts are the most frequently used substitutes in animals and human studies. Twenty-three patients have undergone bile duct reconstruction using four different substitutes: vein grafts (n = 13), omentum/round ligament (n = 5), jejunum (n = 4), and Teflon (n = 1). Biliary replacement using an autologous vein graft (n = 13) was performed for bile duct injury following cholecystectomy (n = 12) or hepatectomy (n = 1). The 90-day mortality rate was zero. Morbidity occurred within 90 days in two patients (15.4%). Twelve patients were alive at the last follow-up. CONCLUSIONS:Autologous venous graft as a substitute for biliary replacement may be an appealing alternative to RYHJ in hepatobiliary surgery, but this technique is still being developed.

In 2012, a 42-year-old man underwent a right hepatectomy with replacement of the inferior vena cava using a PolyTetraFluoroEthylene (PTFE) prosthesis for hepatocellular carcinoma on a healthy liver. Seven years later, the patient was treated with antibiotics for recurrent bacterial infections. Preoperative computed tomography scanner revealed a thrombotic prosthesis into the duodenum. Venous blood flow bypassed the prosthesis via the enlarged azygos system. We described our surgical procedure to remove the prosthesis with a video and reviewed 11 published cases. Our recommendation is to systematically interpose an omentum flap between prostheses and surrounding digestive structures whenever possible.

We report the case of a patient with cirrhosis with significant portal hypertension who underwent a Resection and Partial Liver Segment 2/3 Transplantation with Delayed Total Hepatectomy procedure using a hypersmall left liver graft with a graft-to-recipient weight ratio of 0.29. To reduce the risk of small-for-size syndrome and modulate portal inflow, a preoperative transjugular intrahepatic portosystemic shunt (TIPS) was placed, decreasing the portosystemic gradient from 15 to 8 mmHg. After transplantation, the TIPS was calibrated and then occluded once sufficient graft hypertrophy was confirmed. This dynamic portal modulation allowed for a safe extended left hepatectomy in the recipient and supported effective graft regeneration. The native liver was explanted after the graft volume reached 1441 mL and accounted for >75% of total liver function. Notably, no small-for-size syndrome occurred. This case suggests that a preoperative TIPS can be considered as part of an individualized, stepwise strategy for portal inflow modulation in selected patients with portal hypertension undergoing RAPID transplantation with hypersmall grafts. Although this report describes a single experience, this strategy represents a promising approach to explore for optimizing portal flow modulation in this context. Further studies are needed to confirm its reproducibility, safety, and potential benefit.

Objective: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). Summary Background Data: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. Methods: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. Results: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. Conclusion: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

Abstract Radioembolization using 90Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons’ exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

Early bifurcation of the common hepatic artery (EBCHA) is a rare anatomical variation (1%), that is often overlooked but can lead to accidental ligation of the right branch of the hepatic artery with consequent arterial ischemia of the right liver and potentially very serious complications during pancreaticoduodenectomy, partial hepatectomy, or liver harvesting for transplantation. It may be difficult to diagnose EBCHA using transverse imaging sections. However, on standard CT sections with intravenous contrast injection, three warning signs should allow the image reader to suspect it: presence of two hepatic arteries to the right of the celiac trunk, presence of a retro-portal hepatic artery, and absence of a right hepatic artery arising from the superior mesenteric artery. Analysis of the CT with reconstruction then allows for definitive diagnosis and limits the risk of accidental arterial injury or ligation.

BACKGROUND:Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS:Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS:The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION:The LT difficulty classification has been validated.

BACKGROUND: Legionnaires disease (LD) is a rare, life -threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell -mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. RESEARCH QUESTION: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? STUDY DESIGN AND METHODS: In this 10 -year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. RESULTS: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground -glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30 -day and 12 -month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12 -month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). INTERPRETATION: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.

La bifurcation précoce de l’artère hépatique commune (BPAHC) est une variation anatomique rare (1%), souvent méconnue, qui peut conduire lors d’une duodénopancréatectomie céphalique, une hépatectomie partielle, ou un prélèvement hépatique pour transplantation à la ligature accidentelle de la branche droite de l’artère hépatique avec une ischémie artérielle du foie droit aux conséquences parfois très graves. La BPAHC n’est pas facile à diagnostiquer en imagerie sur des coupes transversales. Cependant, sur des coupes standard de scanner injecté, trois signes d’alerte permettent de la suspecter : présence de 2 artères hépatiques à droite du tronc cœliaque, présence d’une artère rétro-portale et absence d’artère hépatique droite naissant de l’artère mésentérique supérieure. Une analyse avec reconstruction permet alors le diagnostic de certitude et de limiter le risque de plaie ou de ligature artérielle accidentelle.

Background Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. Research Question What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? Study Design and Methods In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. Results One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). Interpretation LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.