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Review
. 2021 Nov 2;22(21):11905.
doi: 10.3390/ijms222111905.

Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD

Stefania Di Mauro  1 , Alessandra Scamporrino  1 , Agnese Filippello  1 , Antonino Di Pino  1 , Roberto Scicali  1 , Roberta Malaguarnera  2 , Francesco Purrello  1 , Salvatore Piro  1
Affiliations
Review

Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD

Stefania Di Mauro et al. Int J Mol Sci. .

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.

Keywords: NAFLD; biomarkers; ncRNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the main circulating biomarkers in NAFLD. Specific biomarkers for NAFL (non-alcoholic fatty liver), NASH (non-alcoholic steatohepatitis) and hepatic fibrosis. FLI (fatty liver index), HSI (hepatic steatosis index), CAP (controlled attenuation parameter), MRI-PDFF (magnetic resonance imaging proton density fat fraction), TNF (tumor necrosis factor), IL-6 (interleukin 6), IL-1 (interleukin 1), CXCL10 (C-X-C motif chemokine ligand 10), CK18 (cytokeratin 18), APRI (AST to platelet ratio index), BARD score (BMI, AST:ALT ratio, presence of diabetes), FIB-4 (fibrosis 4), NFS (NAFLD fibrosis score), HA (hyaluronic acid), PIIINP (N-terminal type III collagen pro-peptide), Pro-C3 (C-terminal cleavage site of N-terminal type II collagen pro-peptide), TIMP-1 (tissue inhibitor of metalloproteinases 1), MRE (magnetic resonance elastography).
Figure 2
Figure 2
Comparison between commonly used clinical methods and innovative research fields aimed at identifying novel non-invasive biomarkers for simple steatosis, NASH and fibrosis biomarkers.
Figure 3
Figure 3
Schematic representation of circulating RNA biomarkers for NAFLD diagnosis. Circulating RNAs (e.g., mRNAs, miRNAs, lncRNAs and circRNAs) can be embedded in membranous vesicles, associated with RNA binding protein or in a free form. Membranous vesicles, besides RNA, contain other macromolecules, including DNA, proteins and metabolites.
Figure 4
Figure 4
Schematic representation of deregulated noncoding RNA pattern in NAFLD. The figure shows specific miRNAs and lncRNAs associated with NAFL (non-alcoholic fatty liver), NASH (non-alcoholic steatohepatitis) and hepatic fibrosis.
See this image and copyright information in PMC

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