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The impact of statins on patients receiving immune checkpoint inhibitors for advanced hepatocellular carcinoma (aHCC) remains unclear. This study aimed to evaluate whether statins influence overall survival (OS) and progression-free survival (PFS) in aHCC patients receiving Atezolizumab + Bevacizumab (A + B). ARTE is a prospectively maintained dataset of 305 aHCC patients treated with A + B. Among these, 63 patients receiving statins were identified and propensity score-matched to 63 non-statin users. Primary outcomes were OS and PFS, while treatment discontinuation due to liver-related events was assessed as a secondary outcome. The median treatment duration was 6.4 months (IQR 2.7–13.2). Among the 126 matched patients, viral etiology was the most common (44.4%), followed by metabolic dysfunction-associated steatotic liver disease (MASLD) (40.5%). Median OS was 23 months [95% CI 17.2–28.7] in statin users vs. 16 months [95% CI 12.8–19.2] in non-users, while median PFS was 12 months [95% CI 4.1–19.9] in statin users vs. 8 months [95% CI 4.0–12.0] in non-users, with no significant differences between groups. In multivariate Cox regression, MASLD-induced HCC was associated with a higher risk of progression or death (HR 1.68, 95% CI 1.03–2.75). Statins did not reduce the risk of treatment discontinuation due to liver-related events (HR 1.05, 95% CI 0.27–4.14). Statins did not improve OS or PFS, nor did they reduce the risk of treatment discontinuation due to liver-related events in aHCC patients receiving A + B. Notably, MASLD-related HCC exhibited worse PFS, suggesting a potential differential response to systemic therapies, which warrants further investigation.

Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the onset of chronic liver disease, and its propagation promotes liver dysfunction. At the same time, chronic liver disease is characterized by alterations in primary and secondary hemostasis but unlike previously thought, these changes are not associated with an increased risk of bleeding complications. In recent years, the role of coagulation imbalance has been postulated as one of the main mechanisms promoting hepatic fibrogenesis. In this review, we aim to investigate the function of microvascular thrombosis in the progression of liver disease and highlight the molecular and cellular networks linking hemostasis to fibrosis in this context. We analyze the predictive and prognostic role of coagulation products as biomarkers of liver decompensation (ascites, variceal hemorrhage, and hepatic encephalopathy) and liver-related mortality. Finally, we evaluate the current evidence on the application of antiplatelet and anticoagulant therapies for prophylaxis of hepatic decompensation or prevention of the progression of liver fibrosis.

Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies. They are characterized by a peculiar tumor microenvironment and dense vascularization. The importance of signaling between immune cells, endothelial cells, and tumor cells leads to the difficult recapitulation of a reliable in vitro HCC model using the conventional two-dimensional cell cultures. The advent of three-dimensional organoid tumor technology has revolutionized our understanding of the pathogenesis and progression of several malignancies by faithfully replicating the original cancer genomic, epigenomic, and microenvironmental landscape. Organoids more closely mimic the in vivo environment and cell interactions, replicating factors such as the spatial organization of cell surface receptors and gene expression, and will probably become an important tool in the choice of therapies and the evaluation of tumor response to treatments. This review aimed to describe the ongoing and potential applications of organoids as an in vitro model for the study of HCC development, its interaction with the host’s immunity, the analysis of drug sensitivity tests, and the current limits in this field.

The COVID19 pandemic has demonstrated a need for remote learning and virtual learning applications such as virtual reality (VR) and tablet-based solutions. Creating complex learning scenarios by developers is highly time-consuming and can take over a year. It is also costly to employ teams of system analysts, developers and 3D artists. There is a requirement to provide a simple method to enable lecturers to create their own content for their laboratory tutorials. Research has been undertaken into developing generic models to enable the semi-automatic creation of virtual learning tools for subjects that require practical interactions with the lab resources. In addition to the system for creating digital twins, a case study describing the creation of a virtual learning application for an electrical laboratory tutorial is presented, demonstrating the feasibility of this approach.

Recent advancements in understanding how cancer cells evade immune recognition have led to significant progress in cancer immunotherapy. Therapeutic cancer vaccines hold great promise due to their safety, specificity, and ability to establish lasting immune memory, serving as an effective immunotherapy either alone or in combination with other treatments in clinical research. Cancer vaccines aim to restore the host’s innate and adaptive anti-cancer immune responses by stimulating antigen-presenting processes and reversing the immunosuppressive environment that facilitates tumor immune evasion and metastasis. Although in clinical studies cancer vaccines have been observed to not effectively induce tumor regression, they can enhance local immune responses in combination with other immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), thus delaying cancer recurrence and prolonging overall survival in advanced tumor settings.

Hepatitis D virus (HDV) infection affects more than 10 million people worldwide, with an estimated prevalence of nearly 4.5% among HBsAg-positive individuals. Epidemiological studies have shown a significant increase in the prevalence of hepatocellular carcinoma (HCC) in patients with chronic HDV infection compared to those with chronic hepatitis B virus (HBV) mono-infection. Despite the clinical findings, data on molecular oncogenic mechanisms are limited and fragmentary. Moreover, the role of HDV in promoting the development of HCC has so far been controversial, because it is difficult to weigh the respective contributions of the two viruses. In this review, we focused on the direct oncogenic action of HDV, its role in modifying the tumor microenvironment, and the genetic signature of HDV-related HCC, comparing these features with HBV-related HCC.

Patient-derived organoids (PDOs) have emerged as promising preclinical models for studying tumor biology and testing therapeutic strategies in oncology. These three-dimensional culture systems retain key histological, genetic, and functional characteristics of the original tumors, offering a unique opportunity to advance personalized medicine approaches in liver cancer. In this study, we present the methodological framework and preliminary findings of a prospective study aimed at generating and characterizing PDOs from patients with hepatocellular carcinoma (HCC) undergoing surgical resection. Tumor specimens were processed using an optimized protocol for organoid derivation, expansion, and cryopreservation. We evaluated the success rate of organoid establishment and the histo-molecular fidelity to the parental tumor. These early results demonstrate promising engraftment efficiency and maintenance of tumor-specific markers across passages. Our work highlights the potential of PDOs as a reliable and scalable platform for translational research in HCC, setting the stage for future applications in drug screening and biomarker discovery.

Additive manufacturing (AM) of complex geometries faces limitations in the dimensional and geometrical accuracy, especially when the geometries are characterised by thin features designed to tailor the mechanical and thermal properties of novel heat exchangers (HXs). In this work, a novel, complex, thin hollow-walled lattice compact HX was fabricated using the Powder Bed Fusion-Laser Beam on Metal (PBF-LB/M) process. Given the intricate relationships between process parameters and complex design, machine learning (ML) methods were utilised to optimise the manufacturing workflow. Although new ML models would be required for different cases to ensure optimal performance, the flexibility of such approaches allows for recalibration and re-optimisation whenever there are changes to material properties, geometry, or manufacturing settings. A process map for the A205 Aluminium alloy was generated, investigating metallurgical defects and surface quality. Optimal process parameters for defect-free materials were estimated using a neural network (NN). Further, optimisation evaluated the influence of laser parameters, beam compensation (BC), and contour distance (CD), on the geometrical and dimensional accuracy of thin features, with a second NN predicting optimal BC and CD. Thickness deviations in hollow lattices were reduced to under 2%. A prototype of the novel HX using optimised parameters was successfully fabricated and characterised to evaluate manufacturing feasibility. The analysis of pores in thin features, potentially leading to leakage and part failure, was carried out through SEM analysis. While PBF-LB/M is well-established for HXs, this study demonstrates its capability for manufacturing highly complex, thin-walled designs when guided by ML-based optimisation. Graphical Abstract

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as “hepatocellular carcinoma”, “immune checkpoint inhibitors”, “systemic therapy”, “portal hypertension”, “variceal bleeding” and “tyrosine kinase inhibitors”. Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.

Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut–liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways. A few data exist on the role of the gut microbiota or bacteria resident in the biliary tract in the pathogenesis of CCA, and some microbial metabolites, such as choline and bile acids, seem to show an association. In this review, we analyze the impact of the gut microbiota and its metabolites on HCC and CCA development and the role of gut dysbiosis as a biomarker of hepatobiliary cancer risk and of response during anti-tumor therapy. We also discuss the future application of gut microbiota in hepatobiliary cancer management.