Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
Semin Liver Dis. 2020 Aug;40(3):307-320. doi: 10.1055/s-0040-1708876. Epub 2020 Apr 2.
Chronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cells (HSCs) and macrophages play critical roles in fibrosis and HCC. These two cell types interplay and remodel the ECM and immune microenvironment in the fibrotic liver. Once HCC develops, HCC-derived factors influence HSCs and macrophages to switch to protumorigenic cell populations, cancer-associated fibroblasts and tumor-associated macrophages, respectively. This review aims to summarize currently available data on the roles of HSCs and macrophages in liver fibrosis and HCC, with a focus on their interaction.
慢性肝损伤由病毒性肝炎、酗酒和代谢紊乱引起，是一个全球性的健康问题。慢性肝损伤治疗不充分可导致纤维化，导致肝功能障碍和癌变。大多数肝细胞癌（HCC）发生在纤维化的肝脏中。肝纤维化的病理特征包括细胞外基质（ECM）积累、间充质细胞激活、免疫失调和血管生成，所有这些都有助于癌前环境，支持肿瘤的发展。在肝细胞中，肝星状细胞（HSCs）和巨噬细胞在纤维化和 HCC 中起着关键作用。这两种细胞类型相互作用，重塑纤维化肝脏中的 ECM 和免疫微环境。一旦 HCC 发生，HCC 衍生的因子影响 HSCs 和巨噬细胞分别向促肿瘤细胞群（即癌症相关成纤维细胞和肿瘤相关巨噬细胞）转化。本综述旨在总结目前关于 HSCs 和巨噬细胞在肝纤维化和 HCC 中的作用的相关数据，重点关注它们的相互作用。
