miRNA Signature in NAFLD: A Turning Point for a Non-Invasive Diagnosis

Abstract

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.

Keywords: HCC; MBOAT7; NASH; PNPLA3; TM6SF2; epigenetics; fibrosis; intestinal permeability; microRNAs; non-alcoholic liver disease.

Figure 1

Role of miRNAs in progressive NAFLD. Schematic illustration of candidate miRNAs demonstrated to affect the progression of liver damage. In this figure, we reported the relative miRNA expression in different hepatic cell types (hepatocytes, inflammatory cells i.e., Kupffer cells, HSCs) and tissues (gut and VAT) influencing early and late stages of liver injury. Several miRNAs can be secreted into the circulation triggering steatosis onset, inflammation and ECM deposition. Circulating miRNA can be released via passive (i.e., cell death in apoptotic bodies) or active processes inside exosomes, micro vesicles, HDL and AGO2 and can be easily detected in blood circulation as diagnostic, prognostic and predictive biomarkers.