Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (NASH) are chronic hepatic conditions leading to hepatocellular carcinoma (HCC) development. According to the recent “multiple-parallel-hits hypothesis”, NASH could be caused by abnormal metabolism, accumulation of lipids, mitochondrial dysfunction, and oxidative and endoplasmic reticulum stresses and is found in obese and non-obese patients. Recent translational research studies have discovered new proteins and signaling pathways that are involved not only in the development of NAFLD but also in its progression to NASH, cirrhosis, and HCC. Nevertheless, the mechanisms of HCC developing from precancerous lesions have not yet been fully elucidated. Now, it is of particular importance to start research focusing on the discovery of novel molecular pathways that mediate alterations in glucose and lipid metabolism, which leads to the development of liver steatosis. The role of mTOR signaling in NASH progression to HCC has recently attracted attention. The goals of this review are (1) to highlight recent research on novel genetic and protein contributions to NAFLD/NASH; (2) to investigate how recent scientific findings might outline the process that causes NASH-associated HCC; and (3) to explore the reliable biomarkers/targets of NAFLD/NASH-associated hepatocarcinogenesis.
非酒精性脂肪性肝病（NAFLD）或代谢功能障碍相关脂肪性肝病（MASLD）及其伴发的脂肪性肝炎（NASH）是导致肝细胞癌（HCC）发生的慢性肝脏疾病。根据近期提出的"多重平行打击假说"，NASH可能由代谢异常、脂质堆积、线粒体功能障碍以及氧化应激和内质网应激共同引发，且可见于肥胖与非肥胖患者。近期转化医学研究发现，多种新型蛋白及信号通路不仅参与NAFLD的发生发展，还推动其向NASH、肝硬化和HCC演进。然而，肝癌从前驱病变发展的具体机制尚未完全阐明。当前亟需开展针对糖脂代谢异常介导肝脏脂肪变性分子通路的研究，其中mTOR信号通路在NASH向HCC转化中的作用备受关注。本综述旨在：（1）系统阐述NAFLD/NASH相关新型遗传与蛋白因子的最新研究进展；（2）探讨近期科学发现如何揭示NASH相关HCC的发生过程；（3）探索NAFLD/NASH相关肝癌发生的可靠生物标志物与治疗靶点。
肿瘤(癌症)患者之家