Ospedale Civile di Baggiovara, UOC Medicina Metabolica, Dipartimento di Medicina Interna Generale, d'Urgenza e post Acuzie, Azienda Ospedaliero-Universitaria di Modena, Via Giardini 1135, 41125 Modena, Italy.
Internal Medicine Unit, Department of Digestive Diseases, S.Orsola-Malpighi Hospital, Via Massarenti 9, 40136 Bologna, Italy.
Int J Mol Sci. 2020 Aug 16;21(16):5888. doi: 10.3390/ijms21165888.
Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of , to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.
基于这样一种假设，即描述疾病的历史有助于改进实践并为研究提供线索，本文旨在回顾成人和儿童非酒精性脂肪性肝病（NAFLD）的历史。为此，我们探讨了 NAFLD 组织病理学的历史，该历史始于 1980 年 Ludwig 的开创性研究，尽管之前的研究可以追溯到 19 世纪。此外，总结了遗传 NAFLD 定义的主要里程碑。接下来，具体描述了我们对 NAFLD 与代谢综合征之间关联的认识随时间的演变，从过时的概念到更合适的考虑，即 NAFLD 与代谢综合征之间存在相互的双向关系。此外，我们还报告了从最初的直觉到最近的研究的演变，支持 NAFLD 作为心血管疾病的独立危险因素。这种关联可能有很深的根源，可以追溯到古代中东文化，在当时肝脏的重要性与当今社会中心脏的重要性相似。相反，NAFLD 是肝细胞癌和肝外癌症的前兆的概念则是更为现代的。有趣的是，几十年后，肝脏病学会才发布了与 NAFLD 相关的指南。对这些文件的比较分析定义了共同的态度（例如，超声检查和生活方式改变是最初的方法）和分歧的关键点（例如，酒精摄入量的阈值，筛查方法，肝纤维化的最佳非侵入性评估和药物治疗选择）。最后，回顾了 NAFLD 一般、细胞和分子发病机制的主要历史步骤。我们的结论是，深入了解疾病的历史可以帮助我们更好地理解疾病本身，并预测未来 NAFLD 研究的发展方向。
