Transjugular Intrahepatic Portosystemic Shunt Is Associated With Better Waitlist Management of Liver Transplant Candidates With Hepatocellular Carcinoma.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension complications. Its impact on hepatocellular carcinoma (HCC) remains unclear. We evaluated 42,843 liver transplant candidates with HCC from the Scientific Registry of Transplant Recipients (2002-2022).

Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.

Immunotherapy and Liver Transplantation: A Narrative Review of Basic and Clinical Data.

Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation.

Anti-CD122 antibody restores specific CD8 T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth.

Nonalcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). Although immunotherapy is used as first-line treatment for advanced HCC, the impact of NASH on anticancer immunity is only partially characterized. We assessed the tumor-specific T cell immune response in the context of NASH.

FGF21 negatively affects long-term female fertility in mice.

Objective: Obesity and associated liver disease are a growing public health concern. Pharmacological agents to treat non-alcoholic fatty liver disease are limited. FGF21, a hormone secreted by the liver and potent metabolic modulator, is a promising therapeutic target for this indication with several analogs currently in clinical development.

Antibody-induced NKG2D blockade in a rat model of intraportal islet transplantation leads to a deleterious reaction.

Intraportal islet transplantation is plagued by an acute destruction of transplanted islets. Amongst the first responders, NK cells and macrophages harbour an activating receptor, NKG2D, recognizing ligands expressed by stressed cells. We aimed to determine whether islet NKG2D ligand expression increases with culture time, and to analyse the impact of antibody-induced NKG2D blockade in islet transplantation.

Tolerogenic properties of liver macrophages in non-alcoholic steatohepatitis.

Background & Aims: Our understanding of non-alcoholic fatty liver disease (NAFLD) pathogenesis is improving, but there is still limited data on the function of resident liver macrophages in this context, especially when considering their contribution in dampening liver inflammation.

Methods: Liver macrophages were studied in mouse models of prolonged diet-induced liver steatohepatitis and carbon tetrachloride-induced liver injury. We assessed liver macrophages phenotype and costimulatory/inhibitory properties upon exposure to lipopolysaccharide or interleukin 4.

The impact of short-term machine perfusion on the risk of cancer recurrence after rat liver transplantation with donors after circulatory death.

Hypothermic and normothermic ex vivo liver perfusions promote organ recovery after donation after circulatory death (DCD). We tested whether these perfusions can reduce the risk of hepatocellular carcinoma (HCC) recurrence in a 1h-DCD syngeneic transplantation model, using Fischer F344 rats. DCD grafts were machine perfused for 2h with hypothermic perfusion (HOPE) or normothermic perfusion (NORMO), and transplanted.

Chimeric xenotransplantation.

Purpose Of Review: Organ transplantation is an effective treatment for selected patients with end-stage organ disease or specific cancer types. Its main limitations are the chronic lack of grafts and the lifetime need for immunosuppression. The advent of autologous organs generated into xenogeneic species has the potential to solve these issues.

Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner.

Background: Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis.

Methods: We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4).

Effects of remote ischaemic preconditioning on intraportal islet transplantation in a rat model.

Remote ischaemic preconditioning (RIPC), which is the intermittent interruption of blood flow to a site distant from the target organ, is known to improve solid organ resistance to ischaemia-reperfusion injury. This procedure could be of interest in islet transplantation to mitigate hypoxia-related loss of islet mass after isolation and transplantation. Islets isolated from control or RIPC donors were analyzed for yield, metabolic activity, gene expression and high mobility group box-1 (HMGB1) content.

Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.

Areas Covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver.

Chimeric liver transplantation reveals interspecific graft remodelling.

Background & Aims: A major limitation in the field of liver transplantation is the shortage of transplantable organs. Chimeric animals carrying human tissue have the potential to solve this problem. However, currently available chimeric organs retain a high level of xenogeneic cells, and the transplantation of impure organs needs to be tested.

Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma recurrence in the mouse liver.

Background & Aims: There is growing evidence that liver graft ischemia-reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence, but the mechanisms involved are unclear. Herein, we tested the hypothesis that mesenteric congestion resulting from portal blood flow interruption induces endotoxin-mediated Toll-like receptor 4 (Tlr4) engagement, resulting in elevated liver cancer burden. We also assessed the role of remote ischemic preconditioning (RIPC) in this context.

Xenogeneic chimera-Generated by blastocyst complementation-As a potential unlimited source of recipient-tailored organs.

Blastocyst complementation refers to the injection of cells into a blastocyst. The technology allows for the creation of chimeric animals, which have the potential to be used as an unlimited source of organ donors. Pluripotent stem cells could be generated from a patient in need of a transplantation and injected into a large animal blastocyst (potentially of a pig), leading to the creation of organ(s) allowing immunosuppression-free transplantation.

Intraportal islet transplantation: the impact of the liver microenvironment.

The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss.

Dynamic Volume Assessment of Hepatocellular Carcinoma in Rat Livers Using a Clinical 3T MRI and Novel Segmentation.

Purpose: In vivo liver cancer research commonly uses rodent models. One of the limitations of such models is the lack of accurate and reproducible endpoints for a dynamic assessment of growing tumor nodules. The aim of this study was to validate a noninvasive, true volume segmentation method using two rat hepatocellular carcinoma (HCC) models, correlating magnetic resonance imaging (MRI) with histological volume measurement, and with blood levels of α-fetoprotein.

Impact of myeloid-derived suppressor cell on Kupffer cells from mouse livers with hepatocellular carcinoma.

Kupffer cells represent the first line of defense against tumor cells in the liver. Myeloid-derived suppressor cells (MDSC) have recently been observed in the liver parenchyma of tumor-bearing animals. The present study investigates the function of the MDSC subsets, and their impact on Kupffer cell phenotype and function.

An optimized method for mouse liver sinusoidal endothelial cell isolation.

The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non-parenchymal cells were isolated using a modified two-step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods, short-term selective adherence and CD146+ magnetic-activated cell sorting (MACS), and compared in terms of cell yield, viability and purity to our purification technique using CD11b cell depletion combined with long-term selective adherence.

Efficient nonarterialized mouse liver transplantation using 3-dimensional-printed instruments.

Because of the wide availability of genetically modified animals, mouse orthotopic liver transplantation is often preferred over rat liver transplantation. We present a simplified mouse liver transplantation technique and compare transplantation outcomes with versus without hepatic artery anastomosis. Instruments for liver implantation were designed and printed with a 3-dimensional (3D) printer.

Enoxaparin Attenuates Mouse Colon Cancer Liver Metastases by Inhibiting Heparanase and Interferon-γ-inducible Chemokines.

Background/aim: Low-molecular-weight heparin (LMWH) has been suggested to reduce the risk of cancer progression in both preclinical and clinical studies but the underlying mechanisms remain poorly explored. The aim of the study was to investigate the anti-metastatic role of enoxaparin, a clinically-used LMWH, in a murine model of colon cancer and to explore its underlying mechanisms.

Materials And Methods: Using a reproducible mouse model of colon carcinomas, we assessed the capacity of enoxaparin, a LMWH, to affect tumor metastasis of colon carcinoma cell lines in mice.

Enhancement of islet engraftment and achievement of long-term islet allograft survival by Toll-like receptor 4 blockade.

Background: Toll-like receptors are key players in sterile inflammation phenomena and can link the innate and adaptive immune systems by enhancing graft immunogenicity. They are also considered mediators of types 1 and 2 diabetes development. The aim of the present study was to assess the role of Toll-like receptor-4 (TLR4) in mediating the inflammatory and immune responses to pancreatic islets, thereby promoting inflammatory destruction and immune rejection of islet grafts.