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Volume 83 - 2020 - Fasc.2 - Reviews

Angiogenesis in the progression of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and an increasing cause of liver cirrhosis and hepatocellular carcinoma. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a key pathophysiological mechanism contributing to NAFLD progression. Major triggers for angiogenesis in NAFLD include tissue hypoxia, structural and dynamic endothelial cell dysfunction, stellate cell activation and macrophage-mediated inflammation. In turn, angiogenesis drives inflammation and is closely linked to the progression of liver fibrosis and the development of liver cancer. In particular, the molecular crosstalk between pro-angiogenic endothelial cells and activated stellate cells can result in a positive feedback loop in which angiogenesis and fibrosis develop in parallel. In this review, we highlight the molecular mechanisms, drivers and consequences of angiogenesis in the progression of NAFLD to NASH, fibrosis and hepatocellular carcinoma. Evidence from animal and clinical studies suggests that mediators of angiogenesis and endothelial dysfunction are promising disease biomarkers, and that inhibiting angiogenesis may improve the course of NAFLD. (Acta gastroenterol. belg., 2020, 83, 301-307).

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Molecular perspectives for the treatment of hepatocellular carcinoma

Major advances have been performed in the understanding of genomic dysregulation of hepatocellular carcinoma. A median of 40 to 60 somatic mutations in coding sequence per tumor was identified including 2 to 6 mutations per tumor in genes driving liver carcinogenesis. The main genetic alterations target the key signaling pathways of liver carcinogenesis : telomere maintenance, cell cycle gene, Wnt/beta-catenin pathway, epigenetic modifier gene, oxidative stress pathway, AKT/mTOR and Ras/Raf MAP kinase pathways. A genotype/phenotype classification between these genetic drivers the tumor and patient’s features have been also described and was correlated with transcriptomic profiling. These data will be helpful to identify subgroups of HCC that will respond or resist to systemic treatments already used in clinical practice such as tyrosine kinase inhibitors, anti-VEGFR antibody or checkpoint inhibitors and will be useful to identify new therapeutic targets tested in future clinical trials. (Acta gastroenterol. belg., 2020, 83, 309-312).

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