Heyens Leen J M, Busschots Dana, Koek Ger H, Robaeys Geert, Francque Sven
Faculty of Health and Life Sciences, Hasselt University, Hasselt, Belgium.
School of Nutrition and Translational Research in Metabolism, NUTRIM, Maastricht University, Maastricht, Netherlands.
Front Med (Lausanne). 2021 Apr 14;8:615978. doi: 10.3389/fmed.2021.615978. eCollection 2021.
An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs.
在全球范围内，越来越多的人患有或有患非酒精性脂肪性肝病（NAFLD）的风险。NAFLD包括从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH）的不同阶段。NASH是一种肝脏慢性炎症状态，会导致肝星状细胞转化为肌成纤维细胞。这些细胞产生细胞外基质，进而导致肝纤维化。在正常情况下，纤维生成是一种维持组织完整性的伤口愈合过程。然而，持续进展的纤维化可能会致病。这个过程需要很多年，而且通常没有症状。因此，患者通常在出现终末期肝病时才就医，比如肝硬化、失代偿性肝病甚至肝细胞癌。纤维化也被认为是NAFLD患者预后的最重要预测指标。目前，只有少数肝纤维化患者被确定有风险并因此接受治疗。这不仅是因为该疾病大多没有症状，还因为目前肝活检仍是准确检测肝纤维化的金标准。然而，进行肝活检存在一定风险，需要资源和专业知识，因此并非适用于每种临床情况，也不适合用于筛查。因此，已经开发或正在开发不同的非侵入性诊断工具，主要基于血液或其他标本分析或基于影像学。在本综述中，我们将首先概述从单纯性脂肪变性到纤维化演变的致病机制。这为后续讨论当前和未来的诊断生物标志物及抗纤维化药物奠定基础。
