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Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2023; 15(5): 609-640
Published online May 27, 2023. doi: 10.4254/wjh.v15.i5.609
Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease
Dulshan Jayasekera, Phillipp Hartmann
Dulshan Jayasekera, Department of Internal Medicine and Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, United States
Phillipp Hartmann, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California San Diego, La Jolla, CA 92093, United States
Author contributions: Jayasekera D was responsible for writing the manuscript, Hartmann P edited the manuscript.
Supported by National Institutes of Health (NIH), No. K12 HD85036; University of California San Diego Altman Clinical and Translational Research Institute (ACTRI)/NIH, No. KL2TR001444; Pinnacle Research Award in Liver Diseases from the American Association for the Study of Liver Diseases Foundation, No. #PNC22-159963; and the Pilot/Feasibility Grant of the San Diego Digestive Diseases Research Center (SDDRC), No. P30 DK120515 (to P.H.).
Conflict-of-interest statement: All the authors have no conflicts of interest to declare.
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: Phillipp Hartmann, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, United States. phhartmann@health.ucsd.edu
Received: January 29, 2023
Peer-review started: January 29, 2023
First decision: February 23, 2023
Revised: March 14, 2023
Accepted: April 10, 2023
Article in press: April 10, 2023
Published online: May 27, 2023
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide among children and adolescents. It encompasses a spectrum of disease, from its mildest form of isolated steatosis, to nonalcoholic steatohepatitis (NASH) to liver fibrosis and cirrhosis, or end-stage liver disease. The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes. Currently, liver biopsy is the gold standard for diagnosing NAFLD. However, given its invasive nature, there has been significant interest in developing noninvasive methods that can be used as accurate alternatives. Here, we review noninvasive biomarkers in pediatric NAFLD, focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic, sensitivity, and specificity. We examine two major approaches to noninvasive biomarkers in children with NAFLD. First, the biological approach that quantifies serological biomarkers. This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers. The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD. Each of these approaches was applied to children with NAFLD, NASH, and NAFLD with fibrosis. Finally, we suggest possible areas for future research based on current gaps in knowledge.

Keywords: Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Steatosis, Fibrosis, Serological, Imaging

Core Tip: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children and adolescents worldwide. Early diagnosis is essential and currently, liver biopsy is the gold standard for diagnosis and staging. However, noninvasive serological biomarkers, composite scores, and imaging biomarkers are being extensively studied for the diagnosis of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis in children. This work reviews recent research on noninvasive biomarkers in pediatric NAFLD, identifies circulating biomarkers and imaging techniques that show the most promise, and suggests topics for future research.