The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone.
The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone.
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DOI：
10.1055/s-0041-1725023
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发表时间：
2021-05
影响因子：
4.2
通讯作者：
Soto-Gutierrez A
中科院分区：
文献类型：
--
作者：
Haep N;Florentino RM;Squires JE;Bell A;Soto-Gutierrez A
慢性肝损伤会导致肝硬化和终末期肝脏疾病（ESLD），这是全球死亡的主要原因，影响人们生命中最具生产力的时期。药物治疗可以延长生命，但唯一确定的治疗方法是肝移植（LT）。然而，LT仍然受到获得优质供体器官和次优长期结局的限制。从健康功能的肝脏到肝硬化和ESLD的退化涉及肝细胞损伤、肝功能下降和适应的动态过程。然而，对人类肝细胞功能恶化和最终肝衰竭的机制知之甚少。我们回顾了目前对肝硬化和终末期肝病作为一个动态过程的认识，并概述了目前与肝衰竭发展相关的机制，从临床表现到能量适应、再生和核转录因子的调节。新一代治疗方法可以靶向稳定肝细胞分化和功能，以避免肝硬化和ESLD患者需要移植。
Chronic liver injury results in cirrhosis and end-stage liver disease (ESLD) which represents a leading cause of death worldwide, affecting people in their most productive years of life. Medical therapy can extend life, but the only definitive treatment is liver transplantation (LT). However, LT remains limited by access to quality donor organs and suboptimal long-term outcomes. The degeneration from healthy-functioning livers to cirrhosis and ESLD involves a dynamic process of hepatocyte damage, diminished hepatic function, and adaptation. However, the mechanisms responsible for deterioration of hepatocyte function and ultimately hepatic failure in man are poorly understood. We review the current understanding of cirrhosis and ESLD as a dynamic process and outline the current mechanisms associated with the development of hepatic failure from the clinical manifestations to energy adaptations, regeneration, and regulation of nuclear transcription factors. A new generation of therapeutics could target stabilization of hepatocyte differentiation and function to avoid the need for transplantation in patients with cirrhosis and ESLD.
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