Liver cancer international最新文献

Liver fibrosis involves increased extracellular matrix (ECM) deposition, with lysyl oxidase-like 2 (LOXL2) emerging as a key player due to its upregulation in fibrotic tissue. As a member of the lysyl oxidase protein family, LOXL2 contributes to ECM accumulation and remodelling through fibre cross-linking. Its aberrant expression in non-alcoholic steatohepatitis (NASH) implicates it in liver fibrosis. LOXL2 promotes fibrosis by activating hepatic stellate cells, cross-linking ECM proteins, and influencing oxidative stress, inflammation and lipid metabolism. Preclinical studies on LOXL2 inhibitors show promise in reducing fibrosis and improving liver function. Ongoing clinical trials further highlight LOXL2 as a potential anti-fibrotic target. However, challenges such as species differences, tissue-specific effects and the complexity of NASH pathogenesis require additional research. Understanding LOXL2's role in NASH will aid in developing effective treatments for NASH-related fibrosis and liver damage.

Hepatocellular carcinoma (HCC) poses a significant global burden, with most patients being diagnosed at an advanced stage, leading to poor prognosis due to the lack of systemic treatment. The approval of oral tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and anti-angiogenic agents has rapidly expanded the treatment prospects for HCC. However, the use of these drugs has also increased the incidence of portal hypertension (PHT) and upper gastrointestinal variceal bleeding in HCC patients. The diagnosis, screening, emergency treatment, and secondary prevention of upper gastrointestinal variceal rebleeding in advanced HCC patients undergoing oral TKIs therapy have become clinically urgent and critical issues. This review provides an overview of the existing understanding regarding the uses and limitations of transjugular intrahepatic portosystemic shunt (TIPS) insertion for managing HCC in cirrhosis patients with PHT and variceal hemorrhage. Additionally, it explores the potential of TIPS in managing acute upper gastrointestinal bleeding and preventing rebleeding in advanced HCC patients undergoing TKIs therapy. The placement of TIPS within the treatment hierarchy is determined by the specific clinical environment and the individual attributes of the patient.

There is no consensus on which substances and which method should be used for transarterial chemoembolization. A publication commissioned by CIRSE 2021 attempted to formulate recommendations. However, only the spectrum of currently implemented procedures is outlined but no recommendation was made. In this article, therefore, basic considerations regarding the technique of chemoembolization are presented, and the authors discuss fundamental considerations about the embolic materials used, the cytostatic drugs and their dosage, as well as about pain therapy during treatment. Then, a technique is presented which used degradable starch microspheres as an embolic agent. This technique enables multiple treatments over a longer period. However, this proposal is not only evidence-based but also eminence-based. What we need are controlled studies that systematically compare different treatment techniques in a sufficient number of patients. This will hopefully help to find the best method for individual patients. Until then, the technique proposed by the authors can be applied.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Recently, patient care was revolutionized by the introduction of immunotherapy combining anti-programmed death-ligand 1 (PD-L1) checkpoint inhibition with anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for advanced unresectable HCC. Additional promising studies with mono- or combination immunotherapy are in advanced phases of clinical testing. Currently, however, our understanding of which patients profit from immunotherapy and how therapy response may be related to the composition of the tumour immune microenvironment remains incomplete. Inhibitory receptors as targets of immune checkpoint inhibitor (ICI) therapies are strongly expressed by T cells in the tumour microenvironment (TME). However, the HCC microenvironment is highly heterogeneous as illustrated by distinct molecular subtypes and subclassifications with an immune-rich microenvironment representing only a small proportion of HCCs. A better understanding of the tumour immune microenvironment is expected to provide insights for clinically applicable biomarkers to optimize immunotherapies. Recent studies identified subtypes of PD-1 expressing CD8+ T cells with divergent function in the HCC TME associated with different outcomes, suggesting that specific PD-1 expressing CD8+ tissue-resident memory T cells (TRM), but not exhausted CD8+ T cells (TEX), govern positive therapy outcomes. This review discusses the T-cell response in the HCC TME in the context of its heterogeneity, molecular and immune classifications and implications for ICI therapy and biomarker discovery.