Institute of Pathology, Medical University of Graz, Neue Stiftingtalstraße 6, Graz 8010, Austria.
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; Dept of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Vas. Sofias Avenue 76, Athens 11528, Greece.
J Hepatol. 2019 Feb;70(2):294-304. doi: 10.1016/j.jhep.2018.12.003.
Histological fibrosis stage is one of the most important prognostic factors in compensated and decompensated alcohol-related liver disease (ALD). Morphological assessment of fibrosis is useful for patient stratification, enabling individualised management, and for evaluation of treatment effects in clinical studies. In contrast to most chronic liver diseases where fibrosis is portal-based, fatty liver disease (FLD) of alcoholic or non-alcoholic aetiology (NAFLD) is associated with a centrilobular pattern of injury which leads to perivenular fibrosis and/or pericellular fibrosis. Progression of FLD drives expansive pericellular fibrosis, linking vascular structures and paving the way for the development of cirrhosis. At the cirrhotic stage, ongoing tissue damage leads to increasing fibrosis severity due to parenchymal loss and proliferation of fibrous scars. Histologic fibrosis staging systems have been devised, based on topography and the extent of fibrosis, for most chronic liver diseases. The utility of histological staging is reflected in different risks associated with individual fibrosis stages which cannot be reliably distinguished by non-invasive fibrosis assessment. In contrast to NAFLD, ALD-specific staging systems that enable the standardised prognostication required for clinical management and trials are lacking. Although morphological similarities between NAFLD and ALD exist, differences in clinical and histological features may substantially limit the utility of established NAFLD-specific staging systems for prognostication in ALD. This review summarises morphological features of fibrosis in ALD and compares them to other chronic liver diseases, particularly NAFLD. ALD-related fibrosis is examined in the context of pathogenetic mechanisms of fibrosis progression, regression and clinical settings that need to be considered in future prognostically relevant ALD staging approaches.
组织学纤维化分期是代偿和失代偿酒精性肝病（ALD）最重要的预后因素之一。纤维化的形态学评估对患者分层、实现个体化管理以及评估临床研究中的治疗效果都很有用。与大多数慢性肝病中以门脉为基础的纤维化不同，酒精性或非酒精性病因（NAFLD）的脂肪肝疾病与小叶中心损伤模式相关，导致静脉周围纤维化和/或细胞周纤维化。FLD 的进展导致扩展性细胞周纤维化，连接血管结构，并为肝硬化的发展铺平道路。在肝硬化阶段，由于实质损失和纤维性瘢痕的增殖，持续的组织损伤导致纤维化严重程度增加。已经为大多数慢性肝病设计了基于病变位置和纤维化程度的组织学纤维化分期系统。组织学分期的实用性反映在与个体纤维化分期相关的不同风险上，这些风险无法通过非侵入性纤维化评估可靠地区分。与 NAFLD 不同，缺乏用于临床管理和试验的标准化预后所需的特定于 ALD 的分期系统。尽管 NAFLD 和 ALD 之间存在形态学相似性，但临床和组织学特征的差异可能会极大地限制已建立的 NAFLD 特定分期系统在 ALD 预后中的实用性。这篇综述总结了 ALD 中纤维化的形态学特征，并将其与其他慢性肝病进行了比较，特别是 NAFLD。在纤维化进展、消退的发病机制以及未来具有预后相关性的 ALD 分期方法中需要考虑的临床背景下，检查了与 ALD 相关的纤维化。
