Armandi Angelo, Rosso Chiara, Caviglia Gian Paolo, Bugianesi Elisabetta
Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy.
Metabolism. 2025 Jan;162:156080. doi: 10.1016/j.metabol.2024.156080. Epub 2024 Nov 19.
Hepatocellular carcinoma (HCC) is a relevant complication occurring in individuals with advanced Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). Recent epidemiological data suggest an alarming increase in the HCC burden worldwide, with a relevant proportion attributable to MASLD (up to 38 %), either in cirrhotic or non-cirrhotic livers. In view of the changing landscape of metabolic syndrome as "silent pandemic", this narrative review aims to provide an updated picture of the burden of HCC in individuals with MASLD. In the complex pathophysiological pathways linking insulin resistance to MASLD and cardiometabolic syndrome, metabolic inflammation appears a relevant driver of systemic as well as organ-specific complications. Novel insights from the field of immunology, gut-derived liver damage, and association with extra-hepatic cancers will be discussed. Finally, strategies for risk-based HCC surveillance (circulating biomarkers, prognostic models and polygenic risk scores) will be provided and the potential impact of novel drug targeting fibrosing Metabolic dysfunction-Associated Steatohepatitis (MASH) on incident HCC will be discussed.
肝细胞癌（HCC）是晚期代谢功能障碍相关脂肪性肝病（MASLD）患者中出现的一种相关并发症。最近的流行病学数据表明，全球HCC负担惊人地增加，其中相当一部分归因于MASLD（高达38%），无论肝脏是否处于肝硬化状态。鉴于代谢综合征作为“无声大流行”的情况不断变化，本叙述性综述旨在提供MASLD患者中HCC负担的最新情况。在将胰岛素抵抗与MASLD和心脏代谢综合征联系起来的复杂病理生理途径中，代谢性炎症似乎是全身以及器官特异性并发症的一个相关驱动因素。将讨论来自免疫学领域、肠道源性肝损伤以及与肝外癌症关联的新见解。最后，将提供基于风险的HCC监测策略（循环生物标志物、预后模型和多基因风险评分），并讨论针对纤维化代谢功能障碍相关脂肪性肝炎（MASH）的新型药物对新发HCC的潜在影响。
