20 Background: Liver transplantation (LTx) for unresectable colorectal liver metastases (uCLM) has gained renewed interest following the 2024 TransMet trial, which provided prospective, randomized evidence supporting its role in selected patients. This increased demand for LTx in Belgium despite the absence of a national protocol in this early adoption phase. Given the modest number of patients transplanted in TransMet (38), SECA-I (21) and SECA-II (15), and the heterogeneity in selection criteria, we retrospectively collected and analyzed all Belgian LTx cases for uCLM to date. Although performed without a uniform protocol, this national, multi-center cohort provides a timely snapshot of clinical practice prior to launching a standardized national framework. Our aim was to consolidate real-world data to inform future practice and to contribute to the international policy making on this emerging LTx indication. Methods: This multicenter retrospective study included all LTx cases for uCLM performed across all six accredited Belgian LTx centers. Patient selection followed local protocols that varied. In all cases, CLM were classified as permanently unresectable and there was no prior extrahepatic disease. Results: Between June 2016 and August 2025, 29 patients underwent LTx for uCLM in Belgium. Median age was 56 years (IQR 50–61), with 69% male. Primary tumors were mostly left-sided (79%). All tumors were MSS; 86% were RAS/BRAF wild type, 7% had a KRAS - and 7% a BRAF mutation. Prior to LTx, patients received a median of 22 chemotherapy cycles (IQR 16–28), in up to two lines of treatment. The first line consisted of a doublet (62%) or triplet (38%) regimen; 93% received targeted therapy. Serious adverse events after LTx occurred in 62%, including three acute rejections and one intraoperative death; no re-transplantations were performed. Median follow-up was 20.5 months (IQR 7.0–35.3). Recurrence occurred in 38%, mainly pulmonary (73%) and peritoneal (27%), with median time to recurrence 6.3 months (IQR 5.3–6.7). 2-year progression-free survival (PFS) was 35.7% (95% CI 12.8–64.9) among 14 patients eligible for analysis; 1-year PFS was 47.6% (95% CI 25.7–70.2) among 21 patients. 2-year overall survival (OS) was 53.3% (95% CI 43.3–74.1) among 15 patients eligible for analysis; 1-year OS was 68.2% (95% CI 45.6–85.8) among 22 patients. Conclusions: LTx for uCLM is feasible in Belgian practice, with encouraging short-term outcomes despite heterogeneous selection criteria and short follow-up. However recurrence was high despite the limited timeframe, though no hepatic recurrences were observed. These retrospective findings should be interpreted cautiously but support further uptake of LTx in clinical practice, while emphasizing the importance of a standardized national protocol for patient selection to improve long-term outcomes.

BACKGROUND:Left liver resection and split liver surgery demand precise anatomical orientation during parenchymal transection, particularly in the context of organ procurement and pediatric liver transplantation. METHODS:We describe the "Arantius hanging maneuver", which involves preserving and transposing the caudal stump of the Arantius ligament into the parenchymal cut surface. A double hanging maneuver using the caudal Arantius' stump and the round ligament consistently guides dissection toward the left biliary plate, enhancing procedural safety. To illustrate its application, we retrospectively reviewed 134 living donor hepatectomies performed between 2015 and 2019 (119 left lateral sectionectomies, 15 left hepatectomies) with donor outcomes assessed at 3 months using the Clavien-Dindo classification. The maneuver was subsequently implemented in 32 split liver procedures (in-/ex-situ). RESULTS:Donor outcomes were favorable, with no complications in 128 donors (95.5%). Postoperative morbidity included three grade II complications (2.2%), one grade IIIa complication (0.7%) treated by percutaneous drainage, and two grade IIIb complications (1.5%) requiring surgical or endoscopic management. No grade IV or V complications occurred. Recipient 1-year biliary complication rate was 15.6%. In split liver procedures, the maneuver also facilitated identification and division of the left biliary plate. CONCLUSIONS:The « Arantius hanging maneuver » is a simple and reproducible technique for left liver resection and splitting procedures, associated with encouraging results in both donors and recipients. The caudal portion of the Arantius ligament, often overlooked, may represent an anatomical beacon precisely guiding the surgeon during the procedure.

BACKGROUND:Early post-transplant T cell-mediated rejection (TCMR) is commonly defined by histology alone. However, isolated early histological rejection after liver transplantation (LT) often resolves spontaneously and may lead to overtreatment, excessive steroid exposure, and avoidable immunosuppression-related morbidity. Clinically meaningful criteria to distinguish patients who truly require treatment remain poorly defined. METHODS:This single-center study included 421 consecutive adult LT recipients undergoing routine day-7 protocol biopsy between 2000 and 2016, managed with a standardized immunosuppression-minimization strategy and complete long-term follow-up. The Seven-Up score integrated day-7 Banff histology (0-9) with a biological score (Bio-score, 0-4) derived from dynamic changes in total bilirubin, platelet count, and eosinophil count between postoperative day 5 and day 7. Very early (< 15 d) clinically relevant rejection was defined as Banff 6-9 combined with Bio-score > 2. Incidence of histological and clinically relevant TCMR, graft survival, patient survival, and diagnostic performance of the Bio-score were analyzed. RESULTS:At day 7, 157 recipients (37.3%) exhibited Banff 6-9 rejection, whereas 264 (62.7%) had Banff 0-5. A biopsy-only strategy would have resulted in steroid treatment in all 157 patients. Application of the Seven-Up score identified only 19 patients (4.5%) requiring very early antirejection therapy, sparing one in three recipients (138 patients, 32.8%). Long-term graft and patient survival were comparable between the treated and untreated groups. The Bio-score demonstrated good diagnostic accuracy for very early clinically relevant TCMR [area under the curve (AUC) = 0.78; 95% confidence interval (CI): 0.68-0.89; P < 0.001), supporting its role as a non-invasive surrogate of early immune activity. CONCLUSIONS:In liver recipients managed with minimized immunosuppression, most early histological TCMR resolved without treatment. Combining histological and biological criteria substantially reduced overtreatment without compromising graft or patient survival. The Seven-Up score provides a pragmatic framework for personalized early post-transplant management and may inform clinical decision-making, endpoint definition, and future trial design. The bio-component of the score may serve as a tool to avoid risky biopsy in partial LT.

BACKGROUND & AIMS:In chronic liver diseases (CLD), when native hepatocytes enter replicative senescence, new hepatocytes are generated through differentiation of reactive cholangiocytes, also known as ductular reaction (DR). However, this mechanism alone is insufficient to prevent liver failure, highlighting the need for a deeper understanding to enhance its therapeutic potential. We hypothesize that signals driving DR reside in the local niche, particularly in extracellular matrix composition and neighboring cells. METHOD:We modeled CLD in mice using carbon tetrachloride injections (3x/week for 6 weeks). Using Opn-iCreERT2; Rosa26RYFP mice, we tracked DR fate, and with Cdh5-iCreERT2; Rosa26RmT/mG mice, we investigated liver sinusoidal endothelial cell (LSEC) lineage and contributions. Mouse liver tissues were analyzed using immunohistochemistry, flow cytometry, reverse-transcription quantitative PCR and Resolve molecular cartography for spatial transcriptomics. Double spheroids were used to study extracellular matrix effects in vitro. Human liver tissues were examined using double immunohistochemistry, and publicly available single-cell RNA-sequencing datasets were analyzed. RESULTS:We identified two populations of ductular reaction (DR) cells: those surrounded by laminin (Lam-DRs) and those lacking laminin (NoLam-DRs). Lam-DRs retained a biliary phenotype, while NoLam-DRs showed increased Hnf4α expression. In vitro, a laminin-rich environment maintained cholangiocyte-specific gene expression, supporting the role of laminin in preserving the biliary phenotype. Lam-DRs were closely associated with capillarized CD34+ LSECs, which expressed profibrotic and laminin-related genes. Preventing LSEC capillarization reduced laminin deposition and enhanced DR-to-hepatocyte differentiation in chronically injured mice. The CD34+ LSEC-laminin-DR complex was also present in human liver disease samples. CONCLUSION:Capillarized CD34+ LSECs maintain the biliary phenotype of DR cells by preventing laminin degradation, thereby limiting their differentiation into hepatocytes. Targeting this axis could enhance liver regeneration and improve outcomes in CLD. IMPACT AND IMPLICATIONS:Chronic liver disease progression is characterized by impaired hepatocyte regeneration, making alternative regenerative pathways, such as ductular reaction-driven hepatocyte formation, of particular interest. This study provides mechanistic insight into how the local microenvironment, specifically capillarized CD34+ liver sinusoidal endothelial cells and laminin deposition, restricts DR plasticity by stabilizing a biliary fate, thereby limiting endogenous regeneration. These findings are relevant for researchers investigating liver regeneration, fibrosis, and cholangiopathies, and for clinicians seeking to understand why regenerative responses remain inefficient in advanced disease. While acknowledging that ductular reaction-derived hepatocytes contribute modestly to overall parenchymal renewal, our results suggest that therapeutically modulating liver sinusoidal endothelial cell capillarization or extracellular matrix remodeling could represent a strategy to enhance regenerative competence in chronic liver disease, warranting further preclinical and translational investigation.

Liver transplantation (LT) for unresectable colorectal liver metastases (CRLM) has regained interest after the TransMet trial, which reported 5-year survival exceeding 70%. However, estimates of transplant benefit (TB) are lacking. This study provides a first external validity assessment of the TransMet criteria and estimates the 5-year TB using a real-world international cohort. A retrospective multicenter study included 61 TransMet-eligible patients with unresectable CRLM who underwent LT between 2006 and 2020 across seven centers. Matching-adjusted indirect comparisons were used to improve comparability, with sensitivity analyses on effective sample size. Survival was analyzed using Kaplan-Meier curves and restricted mean survival time up to 5 years. Weighted multivariable Cox regressions were employed to assess prognostic factors after transplantation. The 5-year restricted mean survival time was identical in the weighted cohort (effective sample size=19) and the TransMet LT arm (51.0 mo). Sensitivity analysis yielded a 5-year restricted mean survival time consistent with residual imbalance (48.2 mo, ESS=35). KRAS mutation (HR: 5.90, 95% CI: 1.89-18.4), right-sided primary tumor (HR: 4.17, 95% CI: 1.40-12.4), and female sex (HR: 5.73, 95% CI: 1.04-31.6) were associated with poorer survival; CEA≥80 ng/mL emerged as a potential prognostic factor (HR: 6.3, 95% CI: 1.73-22.6) across alternative specifications. The estimated 5-year TB of LT versus chemotherapy was 22.5 months (95% CI: 15.5-29.6). The findings of this first real-world assessment of the TransMet trial criteria and 5-year TB estimation in unresectable CRLM point to reasonable prognostic candidates and support evaluating the inclusion of CRLM in LT allocation models. We advocate expanded multicenter data to reach sufficient prognostic stratification through well-calibrated, highly discriminative studies.

Background & aims: Liver transplantation (LT) for colorectal liver metastases (CRLMs) is attracting increasing interest, especially after publication of the TransMet trial. However, multivariable survival analyses are lacking. Here, we performed such an analysis in a multicentre cohort. Methods: We conducted a retrospective multicentre study of 82 patients with CRLMs undergoing LT (from 2006 to 2020) across seven US and European centres, using multivariable Cox, competing-risk models, and extensive sensitivity analyses. Results: Overall survival rates after 1, 3, and 5 years were 93.7%, 73.4%, and 54.9%, respectively. The findings align with an association between higher risk and the female sex (estimated hazard ratio (HR) 4.1, 95% CI: 1.8–9.2), and the following variables: carcinoembryonic antigen >80 μg/L, right-located colorectal cancer (CRC), largest diameter >5.5 cm, KRAS mutation, and absence of previous liver therapy. Other possible associations with higher uncertainty were pN2-positive CRC and the number of nodules (>10). Variables such as progressive disease after pretransplant chemotherapy and time from primary CRC surgery to LT of ≤24 months, exhibited weaker, less consistent associations. Conclusions: This first multivariable survival analysis of LT for CRLM suggests that female sex is associated with worse outcomes, whereas the prognostic strength of the model currently used in clinical practice is not confirmed. Our findings challenge current selection criteria, highlighting the need for improved prognostic models with better discrimination and calibration. Impact and implications: This multicentre retrospective study analysed survival outcomes in 82 patients undergoing liver transplantation for colorectal liver metastases across seven US and European centres. Several factors, including female sex, high carcinoembryonic antigen levels, right-sided colorectal cancer, larger tumours, KRAS mutation, pN2-positive CRC, number of nodules, and no prior liver therapy, were linked to poorer outcomes. The study questions current prognostic models and selection criteria, emphasizing the need for more accurate tools to guide decision-making in patients with colorectal liver metastases.

OBJECTIVE:To evaluate short-term outcomes and identify predictors of morbidity and mortality following multivisceral oncologic resections involving the pancreas. SUMMARY BACKGROUND DATA:Multivisceral resections including the pancreas are required for locally advanced abdominal malignancies but are associated with considerable perioperative risk. While smaller series suggest acceptable outcomes in selected patients, large-scale international data are lacking to guide surgical decision-making and risk stratification. METHODS:This was a retrospective cohort study of 1,283 patients from 31 international centers who underwent multivisceral oncologic resections involving the pancreas. Patient demographics, tumor characteristics, operative details, and 90-day postoperative outcomes were analyzed. RESULTS:The cohort had a mean age of 64.7 years, and 54.7% were male. Distal pancreatectomy was the most frequent procedure (60.5%), and R0 resection was achieved in 60.9% of cases. Ninety-day mortality was 6.9%, highest in patients with gastric adenocarcinoma (16.7%). Major complications (Clavien-Dindo grade III-V) occurred in 34.4% of patients. Higher ASA classification and open surgical approach were independently associated with increased morbidity and mortality. Prolonged operative time was associated with morbidity only. Female gender and treatment at high-volume centers were protective. In patients with pancreatic tumors, resection involving the colon (OR 1.78, p<0.001), stomach (OR 1.33, p = 0.042), or three or more organs (OR 1.75, p = 0.006) significantly increased complication rates. CONCLUSIONS:Multivisceral resections involving the pancreas are associated with relevant perioperative risk. Optimizing patient selection, favoring minimally invasive techniques when feasible in selected patients, and centralizing care to high-volume centers may help improve outcomes for these complex surgical procedures.

>The development of innovative surgical techniques has been a constant and fundamental aspect in liver transplantation(LT) to address chronic organ shortage. Domino liver transplantation(DLT), initially performed by Furtado et al. in Lisbon in 1995, is an innovative technique in which a liver from a patient with a metabolic disorder is transplanted into a recipient with end-stage liver disease [1].

PURPOSE:Radiotherapy can be used as a bridge therapy prior to liver transplantation. Radiotherapy generates immune reactions involving T cells, which are the main effectors of acute cellular rejection after transplantation. Here, we investigated the impact of radiotherapy on acute cellular rejection. MATERIALS AND METHODS:We retrospectively reviewed the data of oncological patients who benefited from liver transplantation. Patients who received radiotherapy prior to liver transplantation ("RT cohort", n=17) were compared to a matched cohort ("NoRTmatched cohort", n=17) obtained through propensity score-matching analysis of the total non-irradiated cohort ("NoRTall" cohort, n=136). The acute cellular rejection was evaluated using the Banff score for rejection (mild:<5, moderate: 5-6, and severe: 7-9) obtained on an early post-transplantation biopsy. Overall and disease-free survival were reported for patients with hepatocellular carcinoma. RESULTS:Median Banff scores was significantly lower for the RT cohort compared to the NoRTall cohort (2.5 versus 5, respectively, P=0.043) but this statistical difference was eliminated after comparison with the NoRTmatched cohort (median: 4, P=0.62). The 5-year overall and disease-free survival rates were 62 % and 69 %, respectively, for hepatocellular carcinoma patients of the RT cohort (n=14) and did not differ from the 5-year overall (83 %, P=0.15) and disease-free survival rates (90 %, P=0.05) of those of the NoRTmatched cohort (n=16). CONCLUSION:Radiotherapy given prior to liver transplantation did not impact the rate or severity of acute cellular rejection. Furthermore, overall and disease-free survival rates were not impacted by radiotherapy.

3561 Background: Liver transplantation (LT) has recently proved to improve the survival of selected patients with unresectable colorectal liver metastases (uCRLM) compared to chemotherapy (C) alone. However, recurrence rates remain high, stressing the need for a better patient selection. This exploratory study aimed to identify prognostic factors associated with recurrence and death in patients undergoing LT as part of the TransMet trial. Methods: Data from 36 patients of the LT+C arm (per protocol population) were analyzed including age, gender, TNM and RAS status of the primary tumor, characteristics of metastases at diagnosis and at LT, chemotherapy regimen, tumor response (RECIST), and timeframe from primary resection to LT. Associations with recurrence and death were explored. Variables with > 5 observations per group and p-values ≤ 0.10 in univariable analysis were included in multivariable models. Results: Among the 36 transplanted patients, 27 experienced recurrence and 9 died after 50-month follow-up. Recurrence: At univariable analysis two factors were associated to a higher risk: serum CEA levels > 5 ng/ml at time of LT (11/11 vs 11/18, p 0.01) and oxaliplatin-based first line chemotherapy (14/16 vs 13/20, p 0.04). Two other factors showed a trend toward statistical significance: Female sex (14/15 vs 13/21, p 0.10) and > 20 metastases at diagnosis (11/17 vs 16/19, p 0.09). At multivariable analysis, CEA levels at LT > 5 ng/ml (HR: 2.91; 95% CI: 1.0–8.2; p 0.04) emerged as an independent predictor of recurrence. Female sex (HR: 2.2; 95% CI: 0.8–5.3; p 0.08) and oxaliplatin-based first line chemotherapy (HR: 2.0; 95% CI: 0.8–4.8; p 0.13) were also associated with around 2-fold higher risk of recurrence, although not reaching statistical significance. Death : At univariable analysis,two factorswere significantly associated with a higher risk: female sex (7/15 vs 2/21 for male, p 0.03) and > 24 cycles of chemotherapy before LT (8/19 vs 1/15, p 0.05). Two other factors showed a trend toward higher mortality: no response to 1 st line chemotherapy (6/14 vs 3/22, p 0.06) and stable disease (vs partial response) before LT (8/22 vs 1/14, p 0.08). At multivariable analysis, female sex emerged as independent predictor of death (HR 5.1; 95% CI: 1.0-25.0; p = 0.04). More than 24 cycles of chemotherapy (HR 7.1; 95% CI: 0.9 – 51.0; p 0.07) and stable disease (vs partial response) at LT, showed an approximately 7-fold increase in the risk of mortality, although not reaching statistical significance. Conclusions: Within the limits of a reduced sample size, these results suggest that LT should be envisaged early in the history of potential candidates to LT to reduce the number of cycles of chemotherapy. Both morphological and biological tumor response, initially and at time of LT, are essential. The notable influence of female sex on post-LT outcome needs to be further explored. Clinical trial information: NCT02597348 .

Background:Graft steatosis and fibrosis detection is a challenge to avoid graft loss. The role of liver biopsy (LB) after liver transplantation (LT) is changing with the emergence of non-invasive tests. Our aim is to evaluate the accuracy of transient elastography (TE) in predicting steatosis and fibrosis post-LT. Methods:This prospective study was performed on 158 LT patients. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were carried out prior to LB. We built receiver operating characteristic (ROC) curves to evaluate the predictive performance of TE. Results:Using CAP, the area under the curve (AUC) were 0.872 [95% confidence interval (CI): 0.791-0.953, P=0.01] and 0.708 (95% CI: 0.614-0.801, P<0.001) for the diagnosis of steatosis ≥ S2 and ≥ S1, respectively. Using LSM, the AUC were 0.588 (95% CI: 0.486-0.691, P=0.10) and 0.651 (95% CI: 0.480-0.822, P=0.10) for the diagnosis of fibrosis ≥ F2 and F3-F4, respectively. Cut-offs for CAP were 246.5 dB/m for S1 and 275.5 dB/m for S2. Cut-offs for LSM were 7.65 kPa for ≥ F2 and 9.25 kPa for ≥ F3. Conclusions:TE may be useful for screening advanced fibrosis and, interestingly, steatosis after LT. TE might gain relevance to track graft metabolic dysfunction and to propose lifestyle interventions.

Background: Thrombocytopenia is common in pediatric patients with cirrhosis, but the extent and relevance of functional platelet defects remain unclear. Objectives: This proof-of-principle study aimed to characterize platelet properties in cirrhotic children before living-donor liver transplantation using state-of-the-art platelet-based assays, hypothesizing that primary hemostasis in this group is well preserved. Methods: From January 2022 to July 2023, pediatric cirrhotic patients were prospectively enrolled 1 day before liver transplantation. An age-matched control group was included. Platelet functionality was assessed using flow cytometry and microfluidic assays, along with plasma proteins including von Willebrand factor (VWF), a disintegrin and metalloproteinase with a thrombospondin type 13, and soluble glycoprotein VI. A subset of patients was also re-evaluated 3 months after transplant. Results: Twenty-seven pediatric cirrhotic patients, primarily with cholestatic liver disease, and 15 controls were enrolled. Patients had pediatric end-stage liver disease scores from-10 to 44. Flow cytometry revealed subtle platelet activation in the absence of agonists and reduced activation with high agonist concentrations. Micro-fluidic assays revealed variations in platelet thrombus formation among the patients, identifying 2 distinct subgroups: 1 with severe liver disease and higher platelet counts, showing preserved primary hemostasis, and another with lower platelet count and moderate platelet thrombus impairment. High VWF levels likely compensated for reduced platelet activation under high shear. Conclusion: Two subgroups with differences in platelet thrombus formation under flow were identified pretransplantation, likely depending on severity of liver disease, platelet count, and VWF levels. Whether the need for platelet intervention is different between these subgroups requires further clinical investigation.