Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is rising in global incidence and mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disease, is strongly linked to metabolic conditions that can progress to liver cirrhosis and HCC. Iron overload (IO), whether inherited or acquired, results in abnormal iron hepatic deposition, significantly impacting MASLD development and progression to HCC. While the pathophysiological connections between hepatic IO, MASLD, and HCC are not fully understood, dysregulation of glucose and lipid metabolism and IO-induced oxidative stress are being investigated as the primary drivers. Genomic analyses of inherited IO conditions reveal inconsistencies in the association of certain mutations with liver malignancies. Moreover, hepatic IO is also associated with hepcidin dysregulation and activation of ferroptosis, representing promising targets for HCC risk assessment and therapeutic intervention. Understanding the relationship between hepatic IO, MASLD, and HCC is essential for advancing clinical strategies against liver disease progression, particularly with recent IO-targeted therapies showing potential at improving liver biochemistry and insulin sensitivity. In this review, we summarize the current evidence on the pathophysiological association between hepatic IO and the progression of MASLD to HCC, underscoring the importance of early diagnosis, risk stratification, and targeted treatment for these interconnected conditions.
肝细胞癌（HCC）作为原发性肝癌最常见的类型，其全球发病率和死亡率正持续上升。代谢功能障碍相关脂肪性肝病（MASLD）是慢性肝病的主要病因之一，与多种代谢异常密切相关，并可进展为肝硬化及HCC。铁过载（IO）无论源于遗传性或获得性因素，均会导致肝脏铁异常沉积，显著影响MASLD的发生及其向HCC的进展。尽管肝脏IO、MASLD与HCC之间的病理生理联系尚未完全阐明，但糖脂代谢紊乱及IO诱导的氧化应激已被视为关键驱动机制。对遗传性IO的基因组分析显示，特定基因突变与肝脏恶性肿瘤的关联性存在不一致现象。此外，肝脏IO还与铁调素调节异常及铁死亡激活相关，这为HCC风险评估和治疗干预提供了潜在靶点。深入理解肝脏IO、MASLD与HCC之间的关联，对于推进针对肝病进展的临床策略至关重要，特别是近期针对IO的疗法在改善肝脏生化指标和胰岛素敏感性方面已显示出潜力。本综述系统总结了当前关于肝脏IO与MASLD向HCC进展的病理生理关联证据，强调了对这些相互关联的疾病进行早期诊断、风险分层及靶向治疗的重要性。
肿瘤(癌症)患者之家