Liver fibrosis is characterised by the excessive deposition of extracellular matrix (ECM) in response to chronic and sustained liver damage, triggering a prolonged wound healing response. The accumulation of ECM proteins disrupts the normal hepatic architecture, resulting in the development of fibrotic scars and nodules of regenerated hepatocytes, ultimately progressing to cirrhosis. While the acute wound healing response can be transiently initiated, its progression to fibrosis requires chronic exposure to damaging agents, including viral infections, autoimmune disorders, alcohol and drug abuse, cholestatic conditions, and metabolic diseases. Cirrhosis represents an advanced stage of liver disease characterised by distorted liver parenchyma, nodule formation, hepatic dysfunction or insufficiency and reduced intrahepatic blood flow leading to portal hypertension.1–3 Hepatic stellate cells (HSCs), also termed Ito cells, lipocytes, fat storing or perisinusoidal cells, play a pivotal role in liver fibrosis regardless of its aetiology. They act as major producers of ECM and amplify the fibrogenic response.1 2 In a healthy liver, HSCs reside in the space of Disse in between hepatocytes and liver sinusoidal endothelial cells (LSEC). On liver injury, HSCs undergo activation and differentiation into myofibroblast-like cells, a process that is characterised by proliferation, contraction, inflammation and gain of fibrogenic capabilities. Activated HSCs migrate throughout the liver and thereby accumulate in damaged areas where they are replacing injured …

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靶向肝星状细胞对抗肝纤维化：我们的立场如何？

肝纤维化的特点是细胞外基质（ECM）过度沉积，以应对慢性和持续的肝脏损伤，从而引发长期的伤口愈合反应。 ECM蛋白的积累破坏了正常的肝脏结构，导致纤维化疤痕和再生肝细胞结节的发展，最终进展为肝硬化。虽然急性伤口愈合反应可以短暂启动，但其进展为纤维化需要长期暴露于破坏性物质，包括病毒感染、自身免疫性疾病、酒精和药物滥用、胆汁淤积性疾病和代谢性疾病。肝硬化是肝病的晚期阶段，其特征是肝实质扭曲、结节形成、肝功能障碍或肝功能不全以及肝内血流量减少，导致门静脉高压。1–3 肝星状细胞 (HSC)，也称为 Ito 细胞、脂肪细胞、脂肪储存或窦周细胞，无论其病因如何，在肝纤维化中都发挥着关键作用。它们是 ECM 的主要产生者并放大纤维化反应。1 2 在健康的肝脏中，HSC 存在于肝细胞和肝窦内皮细胞 (LSEC) 之间的 Disse 间隙中。在肝损伤时，HSC 会被激活并分化为肌成纤维细胞样细胞，这一过程的特点是增殖、收缩、炎症和获得纤维化能力。激活的 HSC 在整个肝脏中迁移，从而在受损区域积聚，并取代受伤的区域……