Aim: Combined ablation and resection (CARe) is a recognized approach for managing multiple colorectal liver metastases (CRLM). Perioperative and long-term results of laparoscopic versus open CARe were evaluated in this study. Methods: This retrospective multicenter cohort study included CRLM patients who underwent CARe at three hospitals between January 2018 and December 2023. Laparoscopic and open approaches were compared for perioperative and oncological results, with propensity score matching (PSM) applied to reduce baseline imbalance-related bias. Results: Of the 107 CARe procedures, 65 (60.7%) were performed laparoscopically and 42 (39.3%) via open approach. After PSM, patients who underwent laparoscopic CARe had significantly lower intraoperative blood loss (55 vs. 100 mL, P = 0.028) and shorter postoperative hospital stays (6 vs. 8 days, P = 0.005) compared to those who underwent open surgery. However, the complication rates were comparable (P = 0.415). No differences in median recurrence-free survival (14.9 vs. 13.5 months, P = 0.781) or overall survival (70.9 vs. 48.7 months, P = 0.183) were observed. Notably, laparoscopic CARe group had a higher repeat resection rate following intrahepatic recurrence (52.94% vs. 20.00%, P = 0.036). Conclusion: Laparoscopic CARe is a safe and effective approach for multiple CRLM, offering reduced perioperative morbidity and enhanced feasibility of repeat hepatic resection compared with the open approach.

The mechanisms underlying metabolic remodeling in metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Targeting the process of de novo lipogenesis (DNL) in the liver has the potential to mitigate MASLD. Here we show that interferon-related developmental regulator 1 (IFRD1) expression negatively correlates with MASLD/metabolic-associated steatohepatitis (MASH) progression in human liver tissues. In multiple mouse models, Ifrd1-/- mice exhibit an exacerbated MASLD phenotype, while hepatocyte-specific IFRD1 expression suppresses MASH progression. Mechanistically, IFRD1 promotes GLUD1's mitochondrial localization via direct interaction, stabilizing the enzyme's activity to enhance α-ketoglutarate (α-KG) production. α-KG reduces H3K36me3 level at lipogenic genes, thereby inhibiting DNL and ameliorating MASH. α-KG supplementation reverses MASH exacerbation in Ifrd1-CKO mice. Collectively, our research establishes the IFRD1-GLUD1-α-KG axis as a critical metabolic-epigenetic regulatory hub, providing novel targets for inhibiting hepatic DNL and developing therapeutic agents for MASLD/MASH.

Immune checkpoint blockade has improved the treatment of hepatocellular carcinoma (HCC), yet most patients fail to achieve durable responses to PD-1 blockade. Tumor-associated macrophages are major determinants of immunotherapy resistance, but the tumor-intrinsic epigenetic programs that recruit and polarize macrophages in HCC remain incompletely defined. Here, we identify activating transcription factor 2 (ATF2) as a driver of macrophage-mediated PD-1 resistance in HCC. Integrated single-cell and spatial transcriptomic analyses revealed enrichment of M2-like macrophages in non-responding tumors and identified ATF2 as a candidate tumor-intrinsic regulator associated with this immunosuppressive state. Genetic perturbation of ATF2 in syngeneic HCC models demonstrated that ATF2 promotes tumor growth, M2-like macrophage accumulation, CD8+ T-cell dysfunction, and resistance to PD-1 blockade. Mechanistically, ATF2 enhanced CCL2-dependent macrophage recruitment and polarization by coupling transcriptional activation with enhancer remodeling. ATF2 interacted with KAT3A/CBP to increase global and site-specific histone lactylation, particularly H3K18 lactylation, thereby preserving chromatin accessibility at NF-κB-responsive regulatory elements and sustaining inflammatory and chemokine transcription. ATF2 also directly bound the CCL2 promoter, establishing a dual mechanism for CCL2 activation. Pharmacologic inhibition of ATF2 remodeled the tumor immune microenvironment, reduced CD206+ macrophage infiltration, restored CD8+ T-cell effector function, and sensitized orthotopic HCC tumors to PD-1 blockade without overt toxicity. In patient specimens, elevated ATF2 and H3K18 lactylation correlated with NF-κB target expression, CD206+ macrophage enrichment, reduced CD8+ T-cell infiltration, and non-response to anti-PD-1 therapy. These findings define an ATF2-KAT3A-H3K18la-NF-κB chemokine axis that promotes macrophage-mediated immune evasion and nominate ATF2 as a therapeutic target for overcoming PD-1 resistance in HCC.

BACKGROUND:Liver transplantation (LT) is a life-saving therapy for end-stage liver disease, but postoperative neurocognitive recovery and mechanisms remain unclear. Although liver-brain crosstalk is known, whether LT restores neurological dysfunction is uncertain. METHODS:Twenty-one patients undergoing LT were prospectively evaluated within 1-3 d before transplantation and 21 d postoperatively. Cognitive function was assessed using the Montreal Cognitive Assessment and the Psychometric Hepatic Encephalopathy Score, and resting-state electroencephalography (EEG) was analyzed for power spectral density, functional connectivity, and microstate dynamics. Paired plasma samples underwent nontargeted metabolomics, and candidate metabolites were further examined using in vitro inflammatory injury models, patch-clamp electrophysiology, ex vivo brain slices, and in vivo behavioral testing. RESULTS:Montreal Cognitive Assessment scores increased from 23.14 ± 2.46 to 24.67 ± 1.88 (P = 0.0002), and Psychometric Hepatic Encephalopathy Scores improved from -11.28 ± 2.42 to -6.11 ± 2.89 (P < 0.0001) after LT. EEG analyses showed increased alpha1 and beta power, enhanced functional connectivity, and altered microstate dynamics after transplantation. Plasma glial fibrillary acidic protein decreased postoperatively, suggesting reduced neuroinflammatory injury. Nontargeted metabolomics identified postoperative elevation of S-methyl-5'-thioadenosine (MTA), and experimental validation showed that MTA attenuated inflammatory neurotoxicity, reduced reactive oxygen species production, and preserved neuronal excitability and synaptic transmission. CONCLUSIONS:LT was associated with early improvement in neurocognitive function in patients with end-stage liver disease. Integrated EEG and metabolomic analyses suggest that posttransplant cognitive recovery may involve restoration of cortical network activity and systemic metabolic remodeling. MTA emerged as a candidate recovery-associated biomarker and functional metabolite that may contribute to neuroprotection by modulating neuroinflammation.

Background:Steatotic liver disease affects 40% of nonobese individuals, but existing screening tools inadequately detect and stage disease severity in this population because of the limited sensitivity of conventional ultrasound and the lack of dedicated prediction models. Objective:This study aimed to develop and validate an interpretable machine learning model specifically for multiclass hepatic steatosis severity prediction in nonobese individuals to support early risk stratification in this underrecognized group. Methods:Health examination data from 215,145 nonobese participants (BMI <28 kg/m²) were randomly divided into training (n=150,601, 70%) and test (n=64,544, 30%) sets. Hepatic steatosis was diagnosed and graded using the controlled attenuation parameter with established thresholds (none: <248 dB/m; mild: 248-268 dB/m; and moderate to severe: >268 dB/m). From 42 candidate variables, 14 predictors were selected using Least Absolute Shrinkage and Selection Operator regression and Recursive Feature Elimination based on Random Forest importance. Six machine learning algorithms-k-nearest neighbors, naive Bayes, multilayer perceptron, random forest, support vector machine, and Extreme Gradient Boosting (XGBoost)-were developed using 10-fold cross-validation, with hyperparameters optimized for maximal area under the receiver operating characteristic curve (ROC-AUC). Model interpretability was assessed using Shapley Additive Explanations analysis. External validation was conducted in non-Hispanic Asian participants from the National Health and Nutrition Examination Survey (n=726). Model performance was evaluated using accuracy, Cohen κ, ROC-AUC, area under the precision-recall curve, F1-score, precision, sensitivity, and specificity. Results:The final cohort included 215,145 participants, with steatosis severity classified as none (n=92,944, 43.2%), mild (n=54,121, 25.2%), and moderate to severe (n=68,080, 31.6%). Among the 6 machine learning models, XGBoost achieved the best discrimination on the test set, with an accuracy of 0.824 and a macro-average ROC-AUC of 0.941. In external validation, the model maintained strong performance (macro-average ROC-AUC=0.874). Shapley Additive Explanations analysis identified BMI, waist circumference, liver enzymes (alanine aminotransferase and aspartate aminotransferase), renal function indicators (uric acid and serum creatinine), and metabolic indices (triglycerides, continuous metabolic syndrome score, and triglyceride-glucose index) as key contributors to model predictions. The model has been implemented as an online prediction platform to facilitate clinical use. Conclusions:This interpretable XGBoost model accurately predicts controlled attenuation parameter-defined hepatic steatosis severity in nonobese individuals and demonstrates robust performance in both internal and external validation cohorts, providing a practical tool for early risk stratification in this underrecognized population.

Liver metastases can resist T cell immunotherapies, indicating an adaptation of metastatic tumors toward reduced immunogenicity in the liver. Here we show that VSIG4, an immune checkpoint molecule predominantly expressed by Kupffer cells, has an opposing function in determining the growth of liver metastases with distinct antigenicity by modulating cognate T cell antigen receptor signaling through an interaction with CD5. VSIG4-CD5 engagement impedes activation of low-affinity CD8+ T cells while enhancing responses of high-affinity CD8+ T cells by rescuing them from activation-induced cell death. This bidirectional regulation favors the outgrowth of poorly immunogenic metastatic tumor clones and fosters an immune landscape that is unfavorable to T cells as metastatic liver cancer progresses. We also show that blockade of VSIG4-CD5 interaction using a nanoantibody to VSIG4 sensitizes liver metastases to anti-PD-L1 therapy, achieving synergistic efficacy in mice. These findings provide mechanistic insights into cancer immunoediting during liver metastasis and a possible approach for treating immunologically cold tumors.

ABSTRACT The phagocytic function of macrophages plays a crucial role in the innate immune response against tumors. Alpha/beta hydrolase domain‐containing protein 17C (ABHD17C) is a kind of depalmitoyltransferase and its roles in tumor immunology remain largely unclear. This study aims to investigate the role of ABHD17C in the macrophage‐mediated innate immunity in pancreatic cancer (PC). Clinically, ABHD17C is abnormally overexpressed in PC tissues and associated with poor prognosis in patients. Using orthotopic cell‐derived xenograft ‐based NSG murine models, we observed that ABHD17C‐mediated macrophage phagocytic resistance promotes tumor growth in a depalmitoylation‐dependent manner. Mechanistically, ABHD17C‐mediated depalmitoylation of B cell lymphoma 6 member B protein (BCL6B) at Cys442 impedes importin‐α/β‐mediated nuclear translocation of BCL6B and drives its ubiquitination‐dependent degradation in the cytoplasm. The deficiency of nuclear BCL6B attenuates transcriptional repression of the anti‐phagocytic signal CD24, increases its expression, enables PC cells to evade macrophage attack, and ultimately promoting PC progression. Therefore, this study elucidates the mechanism by which the depalmitoyltransferase ABHD17C protects tumor cells from macrophage phagocytosis, which highlights the therapeutic potential of targeting the ABHD17C/BCL6B/CD24 signaling axis by macrophage‐mediated innate immune pathway in PC.

ABSTRACT Background Immune checkpoint inhibitors (ICIs) have shown promise in downstaging hepatocellular carcinoma (HCC) for liver transplantation (LT), enabling previously ineligible patients to meet transplant criteria. However, their use raises concerns about post‐transplant acute rejection (AR) based on data lacking information regarding standardized management pathways and notably perioperative protocols, including immunosuppression protocols and monitoring. Methods This study evaluated 59 LT recipients divided into three groups (two control groups), including 13 ICI‐exposed patients (third group). All groups followed a standardized immunosuppression protocol and monitoring embedded into an enhanced recovery after surgery (ERAS) protocol, featuring basiliximab and steroid induction, early mammalian target of rapamycin inhibitor (mTOR) use, and reduced tacrolimus dosing. Results Despite varied ICI washout intervals (median 36 days), no AR episodes were observed in any group. One‐year overall survival and recurrence‐free survival were 93%/85% and 100%/85% in standard patients, and 77%/69% in ICI‐exposed patients, respectively. The most frequent complications were biliary and infectious, with no significant intergroup differences. Conclusions These findings suggest that in a standardized clinical pathway with structured immunosuppressive protocols, therapeutic drug monitoring, and early complication surveillance, LT can be safely performed after ICI exposure without increasing rejection risk. The study underscores the need for standardized clinical pathways and consistent reporting of immunosuppressive regimens to optimize outcomes in this emerging patient population.

Objective:To investigate the short-term efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with high risk of recurrence after radical resection of hepatocellular carcinoma (HCC).Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinicopathological data of 157 HCC patients with high risk of recurrence after radical resection who were admitted to 6 medical centers, including The First Affiliated Hospital of Nanjing Medical University et al, from June 2021 to February 2023 were collected. There were 128 males and 29 females, aged (59±10)years. Of 157 patients, 101 cases undergoing Donafenib as postoperative adjuvant therapy were divided into the the Donafenib group, and 56 cases under-going no systemic postoperative adjuvant therapy were divided into the control group. Observation indicators: (1) PSM and comparison of general data of patients between the two groups after matching; (2) postoperative treatment; (3) follow-up and survival of patients; (4) analysis of risk factors affecting recurrence-free survival of patients. PSM was done based on the principle of optimal perfect matching, with the clamp value of 0.5, and the Donafenib group and the control group were matched at a ratio of 1.25∶1. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Kruskal-Wallis H test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) PSM and comparison of general data of patients between the two groups after matching. Of 157 patients, 126 cases were successfully matched, including 70 cases in the Donafenib group and 56 cases in the control group, respectively. The elimination of tumor number confounding bias ensured comparability between the two groups after PSM. (2) Postoperative treatment. After PSM, of 70 patients in the Donafenib group, there were 23 cases receiving Donafenib monotherapy, 26 cases combined with transcatheter arterial chemoembolization (TACE), 14 cases combined with immunotherapy, and 7 cases combined with TACE+immunotherapy. Of 56 patients in the control group, there were 37 cases receiving postoperative follow-up alone and 19 cases combined with TACE. (3) Follow-up and survival of patients. All 157 patients were followed up, and the follow-up time of the 101 patients in Donafenib group and the 56 patients in control group were 10.1(range, 6.3-14.6)months and 22.2(range, 15.1-25.5)months, respectively. During the follow-up period, 70 patients in the Donafenib group experienced treatment-related adverse reactions, inclu-ding 8 cases of grade 3 adverse reactions, 23 cases of grade 2 and 39 cases of grade 1 adverse reactions, respectively. After PSM, the postoperative 12-, 18-month recurrence-free survival rates were 83.7%, 83.7% in the 70 patients of Donafenib group and 67.8%, 58.9% in the 56 patients of control group, respectively, showing a significant difference in the postoperative recurrence-free survival time between the two groups ( hazard ratio=0.395, 95% confidence interval as 0.176-0.888, P<0.05). (4) Analysis of risk factors affecting recurrence free survival of patients. Results of multivariate ana-lysis showed that microvascular invasion, vascular thrombus, clinical stage as ⅢA were independent risk factors affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=2.181, 2.612, 2.612, 95% confidence interval as 1.028-4.629, 1.128-6.047, 1.128-6.047, P<0.05), Donafenib as postoperative adjuvant therapy was an independent protective factor affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=0.457, 95% confidence interval as 0.227-0.920, P<0.05). Results of further analysis showed that after PSM, there were significant differences in the postoperative recurrence-free survival time in patients with different clinical factors, including male, age ≥60 years, tumor diameter >5 cm, positive microvascular invasion, positive hepatitis B virus infection, alpha fetoprotein <200 μg/L, between the Donafenib group and the control group ( hazard ratio=0.283, 0.202, 0.174, 0.345, 0.273, 0.180, 95% confidence interval as 0.114-0.707, 0.044-0.937, 0.038-0.794, 0.128-0.929, 0.091-0.819, 0.052-0.620, P<0.05). Conclusion:Donafenib as postoperative adjuvant therapy can effectively reduce the short-term recurrence rate in patients with high risk of recurrence after radical resection of HCC, with good safety and tolerance.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a high incidence in China, largely due to the high prevalence of hepatitis B virus (HBV) infection. HBV‑related HCC often presents with aggressive characteristics but preserved liver function. Resection and ablation are approaches to achieve potentially curative outcomes. However, the recurrence rate is high, with up to 70% within five years. Curative surgery or ablation is used more broadly in China than in Western countries, so identifying patients at high risk of recurrence is essential: risk stratification can inform postoperative management, including surveillance intensity and avoidance of over- or under-treatment. Baseline characteristics provide a simple method of prediction, the impacts of which differ in early and late recurrence. To our knowledge, this is the first narrative review to comprehensively understand the identification, prevalence, and impact of risk factors for both early and late HCC recurrence in Chinese patients following curative‑intent resection or ablation. The review suggests that the most impactful risk factors for early recurrence are aggressive tumor features including tumor size, number and vascular invasion. For late recurrence, key risk factors are patient characteristics such as sex, viral infections and liver cirrhosis. As these risk factors are interrelated, several integrated predictive models like nomograms and artificial intelligence (AI) applications have been proposed, which may enhance risk stratification and inform personalized management strategies. These models should be further validated in large prospective studies to achieve clinical application.

Resistance to tyrosine kinase inhibitors (TKIs) dampens their clinical efficacy in hepatocellular carcinoma (HCC). Stress granules formed by phase separation are essential to stress response and can be involved in therapy resistance, but their mechanisms in HCC are unclear. Here our screen shows that the atypical serine/threonine kinase RIOK1 is highly expressed in HCC, linked to poor prognosis, and transcriptionally activated by NRF2 under various stress conditions. RIOK1 undergoes liquid–liquid phase separation by incorporating IGF2BP1 and G3BP1 into stress granules that sequestrate PTEN messenger RNA reducing its translation. This process activates the pentose phosphate pathway, facilitating stress resolution and cytoprotection against TKI. We further show that the small-molecule inhibitor chidamide downregulates RIOK1 and enhances TKI efficacy. RIOK1-positive stress granules are found in donafenib-resistant tumors from patients with HCC. These findings reveal a link between stress granule dynamics, metabolic reprogramming and HCC progression, offering the potential means to improve TKI efficacy. Meng et al. demonstrate that RIOK1 phase separation leads to PTEN mRNA sequestration and pentose pathway activation resolving cellular stress in hepatocellular carcinoma. Targeting RIOK1 enhances response to tyrosine kinase inhibitors.

Purpose:Liver venous deprivation (LVD; simultaneous portal vein embolization and hepatic vein embolization) has been the latest surgical strategy for rapid future liver remnant (FLR) hypertrophy. The aim of this study was to assess the feasibility, safety, and efficacy of simultaneous LVD following hepatic arterial chemoembolization (TACE-LVD) before major hepatectomy for hepatocellular carcinoma (HCC). Patients and Methods:A retrospective analysis of the outcomes of 23 HCC patients who underwent TACE-LVD at our center between October 2019 and October 2023 was conducted. An assessment of postoperative complications, FLR volume, liver function, and tumor response was performed. Results:All patients successfully underwent TACE-LVD. No other serious complications occurred except in 1 patient who underwent puncture drainage due to excessive pleural effusion. Following TACE-LVD, transaminase levels peak two days before rapidly decreasing and return to preoperative levels within one week. The ratio of FLR to standardized liver volume increased from 35.9% (interquartile range [IQR], 8.6) to 46.4% (IQR, 8.2), with a mean degree of hypertrophy and kinetic growth rate of 13.2% (IQR, 5.4) and 4.4% (IQR, 1.8) per week, respectively. At the first assessment after TACE-LVD, most patients exhibited sufficient FLR for hepatectomy, except for 4 patients with cirrhosis. The modified response evaluation criteria for solid tumor assessment revealed a disease control rate of 95.7%, with only 1 patient (Barcelona Clinic Liver Cancer stage C) developing intrahepatic disease progression. Conclusion:TACE-LVD seems to be a feasible, safe, and effective strategy for rapid FLR hypertrophy. Moreover, TACE-LVD may be a therapeutic choice if insufficient FLR hypertrophy precludes resection. This strategy warrants further exploration.

It is well-documented that early recurrence of hepatocellular carcinoma following liver transplantation can markedly impact patient survival. Accurately identifying patients at risk for early recurrence, followed by timely interventions, could greatly improve the long-term efficacy of liver transplantation. The Milan criteria, the clinical gold standard for selecting patients with a low risk of post-transplant recurrence, fails to exclude high-risk patients with biologically aggressive hepatocellular carcinoma. Accordingly, there is an urgent need to develop and validate an improved model for predicting hepatocellular carcinoma post-liver transplantation. Herein, we established a new model to stratify the risk of early hepatocellular carcinoma recurrence following liver transplantation and facilitate decision-making regarding adjuvant therapy. Our newly established nomogram could predict early recurrence post-liver transplantation more effectively than the Milan criteria. Importantly, we found that adjuvant therapy could significantly benefit high-risk recipients but did not significantly affect low-risk recipients. Based on the new stratification criteria, adjuvant therapy should be actively considered for high-risk patients post-liver transplantation, whereas postoperative follow-up and observation are recommended for low-risk patients. Early recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) can adversely affect long-term patient survival. The Milan criteria (MC) have limited capacity to predict early HCC recurrence, and no consensus regarding prophylactic adjuvant therapy (AT) after LT has been established. Herein, we developed an accurate model for predicting early HCC recurrence following LT to guide decision-making on AT. Overall, 364 patients with HCC from three transplantation centers in China were included and followed up for one-year post-LT. Baseline data were used to construct a nomogram, comparing performance with the MC. The efficacy of AT was compared between patients stratified into low- and high-risk subgroups based on nomogram scores.The nomogram included tumor burden score, alpha-fetoprotein level, platelet-to-lymphocyte ratio, pathological differentiation, and microvascular invasion as independent predictive factors. The concordance index and the area under the curve of the nomogram were 0·768 (95% confidence interval, 0·753-0·781) and 0·809, respectively, exceeding those of the MC. The results of the calibration curve and decision curve analysis were also satisfactory. Considering the high-risk subgroups, the AT group considerably outperformed the No-AT group in terms of 1-year recurrence-free survival (45·0 vs. 23·0%, P < 0·001). However, the low-risk AT and No-AT groups did not significantly differ (78·5 vs. 83·9%). In patients with HCC, the new nomogram predicted early recurrence post-LT more effectively than the MC. Based on the new stratification criteria, high-risk patients may benefit from AT, whereas AT is not recommended for low-risk patients.

Introduction With the continuous advancement of surgical technique,com-bined vascular resection has become increasingly common dur-ing complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to re-store vascular continuity and function.Commonly employed vascu-lar grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and sat-isfying histocompatibility,making it a valuable option for vascular reconstruction.

562 Background: As the sixth most common malignancy worldwide, hepatocellular carcinoma (HCC) accounted for 4.7% of all new cancer diagnoses in 2022. Low- and middle-income countries seem to bear a disproportionate burden of the disease, with over 50% of new HCC cases estimated to occur in China and Africa. Research on multidisciplinary team (MDT) practices in these regions is limited. The objective of this study is to compare MDT practices in the management of HCC in HICs and LMICs. Methods: Data on MDT practices from hospitals that manage HCC in Italy, Spain, Switzerland, Germany, Denmark, Canada and the USA, representing HICs, and in China, South Africa and Egypt, representing LMICs were collected through virtual semi-structured interviews and workshops. Results: Ten key areas of differences were identified (Table 1) that could be categorized as organizational/regulatory or clinical. In HIC institutions, the focus currently is on optimizing MDTs as standard of care approach accessible to all patients with HCC; MDT principles are often integrated into national policies. In LMICs, emphasis is on establishing MDTs and expanding their capacity; patient access to MDT care is not a mandatory requirement, nor regulated in national policy. Of note, LMICs are seeking early technology adoption to overcome some potential barriers to MDT interactions; online formats are more often explored to facilitate participation and AI-assisted diagnostic tools are explored to compensate for absence of radiologists. Absence of screening and surveillance for early detection in HCC is more common in LMICs, and therefore likely that patients more often present with advanced stage disease. Also, with limited diagnostic modalities, diagnostic work-up and staging may be sub-optimal. Conclusions: Significant variation exists in HCC MDT practices between HICs and LMICs. The ultimate goal of this study is to develop a format for clinical MDTs that will facilitate interaction between HICs and LMICs. Consideration for the differences highlighted above is crucial for the development of this concept. 10 key areas highlighting differences identified between HICs and LMICs. MDT development direction: Standard of Care for all patients vs. specific session for complex cases National/regional regulatory requirements Institutionalizing MDT principles MDT composition (specialists) Use of digital tools Reimbursement Access to therapeutic options Stage presentation of HCC patients Use of clinical staging Patient follow-up after MDT discussion

563 Background: HCC MDTs involve specialists collaborating on patient cases to create personalized treatment plans. Implementing MDTs can be challenging in countries with limited resources and high disease burdens. In China, there were 368,000 new liver cancer cases in 2022 representative of 40% of global cases. Therefore, evaluating MDT practices at leading hospitals in China may offer valuable insights that could help improve HCC MDT practices worldwide. Methods: This study selected hospitals with distinct MDT models: one for all new patients and one for complex cases. Hospitals handling over 1,000 HCC cases annually were chosen. Desk research and virtual interviews with MDT members from three leading Chinese hospitals—The First Affiliated Hospital of USTC, The First Affiliated Hospital of SYSU, and Tongji Hospital—were conducted to analyze their MDTs and determine key best practices. Results: We identified 6 key best practice in HCC MDTs at these leading Chinese hospitals. 1) Quality Control on MDT process: Leading hospitals ensure the MDT’s efficient execution and effective outcomes. E.g., USTC established a quality control team to audit the MDT process. 2) Real-World Evidence: Leading hospitals prioritize the construction of real-world databases linked to MDT-care to inform impact on outcomes. E.g., SYSU's preliminary data shows impact of MDT care on survival rates (From 2006 to 2010, 5,627 patients who underwent radical liver cancer resection with MDT care saw their five-year survival rate reach 60%, a notable improvement over historical averages) 3) Comprehensive Teams: These hospitals typically have robust teams, involving around 10 specialties. E.g., Tongji Hospital’s MDTs involve ~10 specialties for holistic care. 4) Patient Journey Coverage: MDTs manage patients from diagnosis to rehabilitation, providing a holistic approach to patient management. 5) Guideline-based treatment decisions: They follow latest guidelines coupled with access to approved therapies to make treatment decisions 6) Training: Young physicians are invited to actively participate in MDT consultations (e.g., through case preparation and presentation, etc.). Conclusions: Evaluation of MDT practices at leading China institutes highlights key best practices that could be adopted to enhance care quality for patients with HCC. The ongoing efforts and successes of these institutions provide a model for broader adoption and standardization of MDT practices across the country.