Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic pathology in industrialized countries, affecting about 25% of the general population. NAFLD is a benign condition, however, it could evolve toward more serious diseases, including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard for NAFLD diagnosis. Due to the risks associated with liver biopsy and the impossibility to apply it on a large scale, it is now necessary to identify non-invasive biomarkers, which may reliably identify patients at higher risk of progression. Therefore, several lines of research have tried to address this issue by identifying novel biomarkers using omics approaches, including lipidomics, metabolomics and RNA molecules’ profiling. Thus, in this review, we firstly report the conventional biomarkers used in clinical practice for NAFL and NASH diagnosis as well as fibrosis staging, and secondly, we pay attention to novel biomarkers discovered through omics approaches with a particular focus on RNA biomarkers (microRNAs, long-noncoding RNAs), showing promising diagnostic performance for NAFL/NASH diagnosis and fibrosis staging.

Triglyceride-Rich Lipoproteins and Glycoprotein A and B Assessed by 1H-NMR in Metabolic-Associated Fatty Liver Disease

“…Interestingly, the association between TRL, Glyc-A and B and the clinical indexes of fatty liver disease was weaker or even null for FIB-4. FIB-4 is considered to be a fibrosis marker rather than an inflammation marker, which could explain this result ( 41 ).…”

Mitochondrial RNAs as Potential Biomarkers of Functional Impairment in Diabetic Kidney Disease

“…This study supports the idea that other classes of RNA molecules could represent useful biomarkers in DKD. Indeed, similarly to microRNAs [ 23 ], other RNA transcripts are resistant to endogenous RNase degradation and easily detectable in biological fluids through basic molecular biology techniques [ 18 ]. Only a few studies analyzed the detection of messenger RNAs or ncRNA for DKD diagnosis/prognosis.…”

“…As far as transcriptomics studies are concerned, they limited their analysis to miRNome expression profiles, although other classes of non-coding RNAs such as mRNAs and non-coding RNAs could be novel biomarkers for DKD [ 17 ]. These molecules, as well as microRNAs, are easily detectable and highly stable in biological fluids and against several pre-analytic conditions, for instance, repeated freeze-thaw cycles, long Room Temperature (RT) incubation and postponed processing of samples [ 18 ].…”

The macrophage-associated microRNA-4715-3p / Gasdermin D axis potentially indicates fibrosis progression in nonalcoholic fatty liver disease: evidence from transcriptome and biological data

“…Moreover, noninvasive estimation systems can evaluate the fibrosis stage in patients without biopsy, with the NAFLD fibrosis score and fibrosis-4 index (FIB-4) commonly used. The complex pathophysiological mechanism of NASH progression remains unrevealed [ 30 , 31 ]. Currently, multiple therapies aimed at several targets, such as changes in the microbiome and intestinal permeability, oxidative stress, insulin resistance, apoptosis, lipotoxicity, inflammation, bile acid metabolism, and fibrogenesis.…”