Hepatobiliary & Pancreatic Diseases International最新文献

Background: Organoids are advanced to mimic the structural and functional features of native organs. Advances in stem cell research and extracellular matrix technology have enabled the generation of organoids for diverse organs. Liver organoids hold significant relevance due to the liver's critical physiological roles and the high morbidity associated with liver diseases. Organoids offer potential for studying disease mechanisms and therapeutic interventions.

Data sources: A literature search was conducted in PubMed and Web of Science for relevant articles published up to December 2024. The keywords used for the search included liver organoid, viral hepatitis, primary liver cancer and non-alcoholic fatty liver disease.

Results: Liver organoids have been successfully utilized to model a spectrum of liver diseases, such as viral hepatitis, primary liver cancer, non-alcoholic fatty liver disease, and other hepatic pathologies. By using liver organoids to simulate the pathological environments of different liver diseases, researchers have discovered that molecular (e.g., miR-122) and signaling pathways (e.g., mTOR signaling pathway) are related to liver diseases. Moreover, novel drugs (e.g., regorafenib) have been identified for the treatment of these liver diseases. Their application has significantly enhanced preclinical research by providing a more physiologically relevant platform compared to traditional models.

Conclusions: Liver organoids represent a transformative tool in hepatology, offering a physiologically relevant platform for disease modeling, drug screening, and regenerative applications. While promising, liver organoids remain limited in replicating native liver complexity. Future efforts should enhance structural maturity, multicellular interactions, and microenvironment integration.

Background: The early recurrence (ER) of hepatocellular carcinoma (HCC) following curative liver resection is closely associated with poor clinical outcomes. This study aimed to develop a radiopathomics signature for predicting the risk of ER after curative-intent resection in patients with HCC.

Methods: This study comprised 287 patients with HCC who underwent curative-intent resection and divided them into a development cohort (n = 200) and an internal validation cohort (n = 87). An independent external validation cohort was obtained from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Radiomics features were extracted from portal venous-phase CT images, and pathomics features were derived from digitized whole slide images (WSIs). Feature selection was performed using support vector machine-recursive feature addition (SVM-RFA) to construct the radiopathomics signature. For comparison, three unimodal models, namely radiomics-only, pathomics-only, and clinical-only, were developed using the same computational framework. Model performance was comprehensively evaluated across both validation cohorts. Furthermore, gene set enrichment analysis (GSEA) was conducted to investigate the biological pathways associated with the radiopathomics signature.

Results: The radiopathomics signature outperformed all unimodal models in predicting ER, yielding area under the curve (AUC) values of 0.887 (95% CI: 0.840-0.935), 0.824 (95% CI: 0.737-0.911), and 0.762 (95% CI: 0.612-0.912) in the development, internal validation, and external validation cohorts, respectively. Stratification based on the radiopathomics score successfully identified the high- and low-risk subgroups with significantly different recurrence-free survival (RFS) outcomes. GSEA further revealed that the high-risk group was enriched in cancer-related and metabolic pathways.

Conclusions: The proposed radiopathomics signature provides a promising approach for predicting postoperative ER in patients with HCC, potentially informing individualized clinical management strategies.

Liver transplantation (LT) is limited by organ shortage, increasingly relying on extended criteria donors (ECD) and donation after circulatory death (DCD) grafts, which are particularly vulnerable to ischemia-reperfusion injury (IRI). Beyond immune activation, IRI is driven by non-immunological mechanisms, including mitochondrial dysfunction, oxidative stress, endothelial injury and biliary damage, which critically affect graft quality. Machine perfusion (MP) offers a mean to directly target these upstream events. Hypothermic oxygenated perfusion/dual-hypothermic oxygenated perfusion (HOPE/D-HOPE) provides controlled mitochondrial reoxygenation, prevents succinate-driven reactive oxygen species (ROS) bursts, activates antioxidant pathways and protects the biliary epithelium, thereby reducing ischemic cholangiopathy (IC). Normothermic machine perfusion (NMP) sustains aerobic metabolism, maintains adenosine triphosphate (ATP) generation and microcirculatory homeostasis, and stimulates autophagy and regenerative pathways. Both strategies consistently reduce early allograft dysfunction (EAD) and improve graft outcomes, particularly in high-risk grafts. In addition, MP enables real-time viability assessment. Known markers, such as lactate clearance and bile composition, are complemented by emerging mitochondrial biomarkers, including flavin mononucleotide (FMN) and nicotinamide adenine dinucleotide (NADH), which directly reflect respiratory chain function and predict post-transplant outcomes. Sequential protocols combining HOPE and NMP maximize both protection and assessment, increasing safe utilization of marginal livers. Altogether, MP represents a therapeutic and diagnostic platform, improving metabolic stability, reducing biliary complications and expanding the donor pool, while moving beyond traditional static preservation.

Bile acids (BAs) represent the terminal products of cholesterol catabolism and are integral to a wide range of physiological processes. The maintenance of BAs homeostasis is essential for human health, with disruptions being implicated in various liver and intestinal disorders. The gut-liver axis, a bidirectional communication network connecting multiple organ systems, plays a crucial role in preserving both metabolic and immune homeostasis. Recent evidence suggests that BAs are key modulators within this axis, influencing intestinal barrier function, immune responses, and the composition of the gut microbiome. This review synthesizes recent advances in our understanding of BAs, including their origins, circulation within the gut-liver axis, and diverse roles in physiology, thereby highlighting the critical functional significance of this BAs-mediated network.

Background: Subcutaneous adipose tissue (SAT) is among the components of body composition. SAT radiodensity (SATr) is an indirect surrogate marker of adipose tissue quality and is associated with a poor prognosis in various malignancies. The present study aimed to evaluate the association of chronological changes in SATr during the preoperative waiting period with postoperative overall survival (OS) in patients with perihilar cholangiocarcinoma undergoing major hepatectomy.

Methods: This study included patients with perihilar cholangiocarcinoma who underwent major hepatectomy and extrahepatic bile duct resection as curative treatment. SATr was evaluated using plain computed tomography images. The chronological changes in SATr were calculated as SATr at surgery minus SATr at diagnosis. SATr changes of > 0 or ≤ 0 Hounsfield units were defined as positive (P-SATr) or negative SATr changes (N-SATr), respectively. The primary outcome was postoperative OS according to the change in SATr. The prognostic factors for OS were also evaluated using a Cox proportional hazard model.

Results: The study enrolled 104 patients, including 75 and 29 patients with P-SATr and N-SATr, respectively. P-SATr was associated with higher serum carcinoembryonic antigen levels and greater amount of adjusted blood loss during the operation. There were no significant differences in the in-hospital mortality and complication rates as well as postoperative hospital stay between the P-SATr and N-SATr groups. The median OS durations were 37.3 and 78.0 months in the P-SATr and N-SATr groups (P < 0.01). Multivariate analysis revealed P-SATr [hazard ratio (HR) = 1.95; 95% confidence interval (CI): 1.02-3.75; P = 0.04], serum carbohydrate antigen 19-9 level > 300 U/mL (HR = 3.68; 95% CI: 1.68-8.07; P < 0.01), presence of lymph node metastasis (HR = 2.04; 95% CI: 1.19-3.50; P < 0.01), and positive residual tumor status (HR = 4.61; 95% CI: 2.21-9.60; P < 0.01) as independent predictive factors for OS.

Conclusions: P-SATr during the preoperative waiting period was associated with poor prognosis in patients with perihilar cholangiocarcinoma undergoing major hepatectomy.