Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Definitive diagnosis of the progressive form, non-alcoholic steatohepatitis (NASH), requires liver biopsy, which is highly invasive and unsuited to early disease or tracking changes. Inadequate performance of current minimally invasive tools is a critical barrier to managing NAFLD burden. Altered circulating miRNA profiles show potential for minimally invasive tracking of NAFLD. The selective isolation of the circulating extracellular vesicle subset that originates from hepatocytes presents an important opportunity for improving the performance of miRNA biomarkers of liver disease. The expressions of miR-122, -192, and -128-3p were quantified in total cell-free RNA, global EVs, and liver-specific EVs from control, NAFL, and NASH subjects. In ASGR1+ EVs, each miR biomarker trended positively with disease severity and expression was significantly higher in NASH subjects compared with controls. The c-statistic defining the performance of ASGR1+ EV derived miRNAs was invariably >0.78. This trend was not observed in the alternative sources. This study demonstrates the capacity for liver-specific isolation to transform the performance of EV-derived miRNA biomarkers for NAFLD, robustly distinguishing patients with NAFL and NASH.
Highlights
Published: 17 January 2022Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting up to a third of the global population [1]
The disease manifests on a spectrum of severity, with most individuals presenting with benign hepatic fat accumulation and approximately 30% exhibiting a more severe form known as non-alcoholic steatohepatitis (NASH) [2]
The concentration and size of global extracellular vesicles (EVs) particles isolated from non-alcoholic fatty fatty liver liver (NAFL), NASH, and control subjects was determined by nanoparticle tracking analysis (NTA)
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting up to a third of the global population [1]. The disease manifests on a spectrum of severity, with most individuals presenting with benign hepatic fat accumulation (nonalcoholic fatty liver; NAFL) and approximately 30% exhibiting a more severe form known as non-alcoholic steatohepatitis (NASH) [2]. Obesity, and other features of the metabolic syndrome are commonly associated with NAFLD, the aetiology of the disease remains largely unknown, with respect to its progression to NASH [3,4]. Higher in individuals with NAFLD compared with those without. The impact on mortality among individuals with NAFLD is proportional to disease severity and ranges from 8.3%
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