General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy.
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano 20122, Italy.
Int J Mol Sci. 2018 Dec 10;19(12):3966. doi: 10.3390/ijms19123966.
Nonalcoholic fatty liver disease (NAFLD) defines a wide pathological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may predispose to liver cirrhosis and hepatocellular carcinoma. It represents the leading cause of hepatic damage worldwide. Diagnosis of NASH still requires liver biopsy but due to the high prevalence of NAFLD, this procedure, which is invasive, is not practicable for mass screening. Thus, it is crucial to non-invasively identify NAFLD patients at higher risk of progression to NASH and fibrosis. It has been demonstrated that hepatic fat content and progressive liver damage have a strong heritable component. Therefore, genetic variants associated with NAFLD have been proposed as non-invasive markers to be used in clinical practice. However, genetic variability is not completely explained by these common variants and it is possible that many of the phenotypic differences result from gene-environment interactions. Indeed, NAFLD development and progression is also modulated by epigenetic factors, in particular microRNAs (miRNAs), which control at post-transcriptional level many complementary target mRNAs and whose dysregulation has been shown to have high prognostic and predictive value in NAFLD. The premise of the current review is to discuss the role of miRNAs as pathogenic factors, risk predictors and therapeutic targets in NAFLD.
非酒精性脂肪性肝病（NAFLD）定义了一个广泛的病理谱，范围从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH），后者可能导致肝硬化和肝细胞癌。它是全球范围内导致肝损伤的主要原因。NASH 的诊断仍需要肝活检，但由于 NAFLD 的高患病率，这种具有侵入性的方法不适用于大规模筛查。因此，非侵入性地识别更有可能进展为 NASH 和纤维化的 NAFLD 患者至关重要。已经证明，肝脂肪含量和进行性肝损伤具有很强的遗传成分。因此，与 NAFLD 相关的遗传变异被提出作为非侵入性标志物，用于临床实践。然而，这些常见变异并不能完全解释遗传变异性，许多表型差异可能是由基因-环境相互作用引起的。事实上，NAFLD 的发生和进展也受到表观遗传因素的调节，特别是 microRNAs（miRNAs），它们在转录后水平上控制许多互补的靶 mRNA，其失调已被证明在 NAFLD 中具有高预后和预测价值。本综述的前提是讨论 miRNAs 作为 NAFLD 的致病因素、风险预测因子和治疗靶点的作用。
