Provera Alessia, Vecchio Cristina, Sheferaw Anteneh Nigussie, Stoppa Ian, Pantham Deepika, Dianzani Umberto, Sutti Salvatore
Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of Piemonte Orientale, 28100, Novara, Italy.
Heliyon. 2024 Jul 31;10(15):e35338. doi: 10.1016/j.heliyon.2024.e35338. eCollection 2024 Aug 15.
Metabolic dysfunction associated steatotic liver disease (MASLD) is a progressive pathological condition characterized by the accumulation of triglycerides within hepatocytes that causes histological changes, which, in the long run, might compromise liver functional capacities. MASLD predisposes to metabolic dysfunction-associated steatohepatitis (MASH), in which the persistence of inflammatory reactions perpetuates tissue injury and induces alterations of the extracellular matrix, leading to liver fibrosis and cirrhosis. Furthermore, these processes are also fertile ground for the development of hepatocellular carcinoma (HCC). In this latter respect, growing evidence suggests that chronic inflammation not only acts as the primary stimulus for hepatocellular malignant transformation, cell proliferation and cancer cell progression but also reshapes the immune landscape, inducing immune system exhaustion and favoring the loss of cancer immune surveillance. Therefore, a thorough understanding of the cellular and molecular mechanisms orchestrating hepatic inflammatory responses may open the way for fine-tuning therapeutic interventions that could, from one side, counteract MASLD progression and, on the other one, effectively treat HCCs.
代谢功能障碍相关脂肪性肝病（MASLD）是一种进行性病理状况，其特征是肝细胞内甘油三酯积累，导致组织学变化，从长远来看，这可能会损害肝脏功能。MASLD易发展为代谢功能障碍相关脂肪性肝炎（MASH），其中炎症反应的持续会使组织损伤持续存在，并诱导细胞外基质改变，导致肝纤维化和肝硬化。此外，这些过程也是肝细胞癌（HCC）发生发展的沃土。在这后一方面，越来越多的证据表明，慢性炎症不仅是肝细胞恶性转化、细胞增殖和癌细胞进展的主要刺激因素，还会重塑免疫格局，导致免疫系统耗竭，有利于癌症免疫监视功能的丧失。因此，深入了解协调肝脏炎症反应的细胞和分子机制，可能为微调治疗干预措施开辟道路，一方面可以对抗MASLD的进展，另一方面可以有效治疗HCC。
