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World J Clin Pediatr. May 9, 2022; 11(3): 221-238
Published online May 9, 2022. doi: 10.5409/wjcp.v11.i3.221
Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics
Simona Riccio, Rosa Melone, Caterina Vitulano, Pierfrancesco Guida, Ivan Maddaluno, Stefano Guarino, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Anna Di Sessa
Simona Riccio, Rosa Melone, Caterina Vitulano, Pierfrancesco Guida, Ivan Maddaluno, Stefano Guarino, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Anna Di Sessa, Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
Author contributions: Riccio S and Di Sessa A wrote the manuscript; Miraglia del Giudice E, Di Sessa A, and Marzuillo P conceived the manuscript; Guarino S, Miraglia del Giudice E, Di Sessa A, and Marzuillo P supervised the manuscript drafting; Riccio S, Melone R, Vitulano C, Guida P, and Maddaluno I reviewed the literature data; Riccio S prepared the tables. Each author contributed important intellectual content during manuscript drafting or revision.
Conflict-of-interest statement: There is no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anna Di Sessa, MD, PhD, Research Fellow, Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Via De Crecchio 2, Naples 80138, Italy. anna.disessa@libero.it
Received: June 30, 2021
Peer-review started: June 30, 2021
First decision: July 30, 2021
Revised: August 5, 2021
Accepted: April 2, 2022
Article in press: April 2, 2022
Published online: May 9, 2022
Processing time: 310 Days and 12.2 Hours
Abstract

As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the “multiple hits” theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).

Keywords: Fatty; Liver; Genetics; Lipidomics; Pediatric

Core Tip: A large body of evidence supported a complex non-alcoholic fatty liver disease (NAFLD) physiopathology with several factors involved in this tangled puzzle. Considering the cardiometabolic burden of NAFLD even in childhood, a better knowledge of NAFLD physiopathology is fundamental for novel therapeutic strategies.