Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury as well as persistent activation of inflammatory response and of fibrogenesis. Liver fibrosis is a major determinant for chronic liver disease (CLD) progression and in the last two decades our understanding on the major molecular and cellular mechanisms underlying the fibrogenic progression of CLD has dramatically improved, boosting pre-clinical studies and clinical trials designed to find novel therapeutic approaches. From these studies several critical concepts have emerged, starting to reveal the complexity of the pro-fibrotic microenvironment which involves very complex, dynamic and interrelated interactions between different hepatic and extrahepatic cell populations. This review will offer first a recapitulation of established and novel pathophysiological basic principles and concepts by intentionally focus the attention on NAFLD/NASH, a metabolic-related form of CLD with a high impact on the general population and emerging as a leading cause of CLD worldwide. NAFLD/NASH-related pro-inflammatory and profibrogenic mechanisms will be analysed as well as novel information on cells, mediators and signalling pathways which have taken advantage from novel methodological approaches and techniques (single cell genomics, imaging mass cytometry, novel in vitro two- and three-dimensional models, etc.). We will next offer an overview on recent advancement in diagnostic and prognostic tools, including serum biomarkers and polygenic scores, to support the analysis of liver biopsies. Finally, this review will provide an analysis of current and emerging therapies for the treatment of NAFLD/NASH patients.

肝纤维化是细胞外基质（ECM）成分的过度沉积，是由慢性肝损伤以及炎症反应和纤维发生的持续激活引起的。肝纤维化是慢性肝病 (CLD) 进展的主要决定因素，在过去的二十年中，我们对 CLD 纤维化进展的主要分子和细胞机制的了解已显着提高，推动了旨在发现肝纤维化的临床前研究和临床试验。新的治疗方法。从这些研究中出现了几个关键概念，开始揭示促纤维化微环境的复杂性，其中涉及不同肝细胞群和肝外细胞群之间非常复杂、动态和相互关联的相互作用。本综述将首先概述已建立的和新颖的病理生理学基本原理和概念，重点关注 NAFLD/NASH，这是一种与代谢相关的 CLD 形式，对普通人群影响很大，并成为全球 CLD 的主要原因。将分析 NAFLD/NASH 相关的促炎和促纤维形成机制，以及有关细胞、介质和信号传导途径的新信息，这些信息利用了新的方法学方法和技术（单细胞基因组学、成像质量细胞术、新型体外双细胞分析）以及三维模型等）。接下来，我们将概述诊断和预后工具的最新进展，包括血清生物标志物和多基因评分，以支持肝活检的分析。最后，本综述将对治疗 NAFLD/NASH 患者的当前和新兴疗法进行分析。