Department of Transfusion Transmitted Diseases, ICMR-National Institute of Immunohaematology, Mumbai 400012, Maharashtra, India.
Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2024 Aug 8;25(16):8641. doi: 10.3390/ijms25168641.
The liver is a complex organ that performs vital functions in the body. Despite its extraordinary regenerative capacity compared to other organs, exposure to chemical, infectious, metabolic and immunologic insults and toxins renders the liver vulnerable to inflammation, degeneration and fibrosis. Abnormal wound healing response mediated by aberrant signaling pathways causes chronic activation of hepatic stellate cells (HSCs) and excessive accumulation of extracellular matrix (ECM), leading to hepatic fibrosis and cirrhosis. Fibrosis plays a key role in liver carcinogenesis. Once thought to be irreversible, recent clinical studies show that hepatic fibrosis can be reversed, even in the advanced stage. Experimental evidence shows that removal of the insult or injury can inactivate HSCs and reduce the inflammatory response, eventually leading to activation of fibrolysis and degradation of ECM. Thus, it is critical to understand the role of gene-environment interactions in the context of liver fibrosis progression and regression in order to identify specific therapeutic targets for optimized treatment to induce fibrosis regression, prevent HCC development and, ultimately, improve the clinical outcome.
肝脏是一个复杂的器官，在体内发挥着重要的功能。尽管与其他器官相比，肝脏具有非凡的再生能力，但化学物质、感染、代谢和免疫损伤以及毒素的暴露会使肝脏容易受到炎症、变性和纤维化的影响。异常信号通路介导的异常伤口愈合反应导致肝星状细胞（HSCs）的慢性激活和细胞外基质（ECM）的过度积累，导致肝纤维化和肝硬化。纤维化在肝癌的发生中起着关键作用。尽管曾经被认为是不可逆转的，但最近的临床研究表明，肝纤维化是可以逆转的，即使在晚期也是如此。实验证据表明，去除刺激或损伤可以使 HSCs 失活并减少炎症反应，最终导致纤维溶解的激活和 ECM 的降解。因此，了解基因-环境相互作用在肝纤维化进展和消退中的作用对于确定特定的治疗靶点以优化治疗以诱导纤维化消退、预防 HCC 发生以及最终改善临床结果至关重要。
