慢性肝病的一致特征和病理修复的标志是所谓的“导管反应”。这是一种组织学异常，其特征是汇管空间内部和周围的畸形胆管细胞扩张，并被炎症细胞、间充质细胞和血管细胞浸润。导管反应是一种高度调控的反应，基于形态发生信号机制的重新激活和多种细胞类型之间的复杂串扰。这些交换的性质和机制决定了健康的再生性肝脏修复和病理性修复之间的差异。细胞类型之间精心策划的信号传导引导间充质细胞沉积具有独特物理和生化特性的特定细胞外基质，定义为门静脉纤维化。纤维化的进展导致巨大的结构和血管变化，称为“肝硬化”。调节这一微环境生态的信号才刚刚开始得到解决。与肿瘤微环境相反，这种“良性”微环境内的免疫调节鲜为人知。原因之一是，导管反应和门静脉纤维化都主要被认为是胆汁淤积性肝病的表现，而这种现象在所有慢性人类肝病中也存在，尽管具有独特的特征。新颖的人类细胞模型和“组学”技术的进步正在快速增加我们的知识。最重要的是，这些知识即将产生新的诊断和治疗进展。在这里，我们将批判性地回顾机制、病理生理学和治疗前景方面的最新进展。此外，我们将描绘未来的研究途径，包括创新的转化机会。版权所有 © 2024 AGA Institute。由爱思唯尔公司出版。保留所有权利。

A consistent feature of chronic liver diseases and the hallmark of pathologic repair is the so-called "ductular reaction." This is a histologic abnormality characterized by an expansion of dysmorphic cholangiocytes inside and around portal spaces infiltrated by inflammatory, mesenchymal, and vascular cells. The ductular reaction is a highly regulated response based on the reactivation of morphogenetic signaling mechanisms and a complex crosstalk among a multitude of cell types. The nature and mechanism of these exchanges determine the difference between healthy regenerative liver repair and pathologic repair. An orchestrated signaling among cell types directs mesenchymal cells to deposit a specific extracellular matrix with distinct physical and biochemical properties defined as portal fibrosis. Progression of fibrosis leads to vast architectural and vascular changes known as "liver cirrhosis." The signals regulating the ecology of this microenvironment are just beginning to be addressed. Contrary to the tumor microenvironment, immune modulation inside this "benign" microenvironment is scarcely known. One of the reasons for this is that both the ductular reaction and portal fibrosis have been primarily considered a manifestation of cholestatic liver disease, whereas this phenomenon is also present, albeit with distinctive features, in all chronic human liver diseases. Novel human-derived cellular models and progress in "omics" technologies are increasing our knowledge at a fast pace. Most importantly, this knowledge is on the edge of generating new diagnostic and therapeutic advances. Here, we will critically review the latest advances, in terms of mechanisms, pathophysiology, and treatment prospects. In addition, we will delineate future avenues of research, including innovative translational opportunities.Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.