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肝纤维化导致肝硬化:基本机制与临床展望。

Liver Fibrosis Leading to Cirrhosis: Basic Mechanisms and Clinical Perspectives.

作者信息

Somnay Kaumudi, Wadgaonkar Priyanka, Sridhar Nidhishri, Roshni Prarath, Rao Nachiketh, Wadgaonkar Raj

机构信息

New York Presbyterian Hospital, Queens, New York, NY 11355, USA.

New York Digestive Disease Center, Queens, New York, NY 11355, USA.

出版信息

Biomedicines. 2024 Sep 30;12(10):2229. doi: 10.3390/biomedicines12102229.

Abstract

Liver fibrosis is the pathological deposition of extracellular matrix rich in fibrillar collagen within the hepatocytes in response to chronic liver injury due to various causes. As the condition advances, it can progress to cirrhosis, the late stages of which are irreversible. Multiple pathophysiological mechanisms and cell types are responsible for the progression of liver fibrosis and cirrhosis. Hepatic stellate cells and myofibroblast activation represent a key event in fibrosis. Capillarization of liver sinusoidal endothelial cells further contributes to extracellular matrix deposition and an increase in portal pressure. Macrophages and neutrophils produce inflammatory cytokines and participate in activating hepatic stellate cells. Although initially believed to be irreversible, early stages of fibrosis are now found to be reversible. Furthermore, advances in noninvasive imaging and serum studies have changed and improved how cirrhosis can be evaluated and monitored. Although there are currently no specific approved therapies to reverse liver fibrosis, management of underlying diseases has been found to halt the progression, and to an extent, even reverse liver fibrosis, preventing further liver injury and cirrhosis-related complications.

摘要

肝纤维化是由于各种原因导致慢性肝损伤后,肝细胞内富含原纤维胶原蛋白的细胞外基质的病理性沉积。随着病情进展,可发展为肝硬化,肝硬化晚期是不可逆的。多种病理生理机制和细胞类型参与了肝纤维化和肝硬化的进展。肝星状细胞和成肌纤维细胞的激活是纤维化的关键事件。肝窦内皮细胞的毛细血管化进一步促进细胞外基质沉积和门静脉压力升高。巨噬细胞和中性粒细胞产生炎性细胞因子并参与激活肝星状细胞。虽然肝纤维化最初被认为是不可逆的,但现在发现其早期阶段是可逆的。此外,无创成像和血清学研究的进展改变并改善了肝硬化的评估和监测方式。虽然目前尚无经批准的特异性疗法来逆转肝纤维化,但已发现对基础疾病的治疗可阻止病情进展,甚至在一定程度上逆转肝纤维化,预防进一步的肝损伤和肝硬化相关并发症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb43/11505165/b3bc605b3d34/biomedicines-12-02229-g001.jpg

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