Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2022; 14(6): 1235-1247
Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1235
Factors early in life associated with hepatic steatosis
Sabrina Xin Zi Quek, Eunice Xiang-Xuan Tan, Yi Ping Ren, Mark Muthiah, Evelyn Xiu Ling Loo, Elizabeth Huiwen Tham, Kewin Tien Ho Siah
Sabrina Xin Zi Quek, Eunice Xiang-Xuan Tan, Mark Muthiah, Kewin Tien Ho Siah, Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
Eunice Xiang-Xuan Tan, Mark Muthiah, National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
Eunice Xiang-Xuan Tan, Mark Muthiah, Kewin Tien Ho Siah, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Yi Ping Ren, Department of Medicine, National University Hospital, Singapore 119228, Singapore
Evelyn Xiu Ling Loo, Elizabeth Huiwen Tham, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
Evelyn Xiu Ling Loo, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore
Author contributions: Tan EXX, Quek SXZ, Kewin STH contributed to study design; Tan EXX, Quek SXZ, Ren YP contributed to data acquisition and data analysis; Kewin STH contributed to study concept and study supervision; All authors contributed to manuscript drafting; Tan EXX, Quek SXZ contributed equally to this manuscript.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Kewin Tien Ho Siah, MBBS, MRCP, Assistant Professor, Doctor, Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, 1E Kent Ridge Road, Singapore 119228, Singapore. kewin_siah@nuhs.edu.sg
Received: January 11, 2022
Peer-review started: January 11, 2022
First decision: February 15, 2022
Revised: March 1, 2022
Accepted: May 27, 2022
Article in press: May 27, 2022
Published online: June 27, 2022
Processing time: 163 Days and 1.6 Hours
ARTICLE HIGHLIGHTS
Research background

Prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has more than doubled in the last two decades, with its downstream complications placing an increasing burden on healthcare systems globally.

Research motivation

At present, there is a paucity of treatment options NAFLD. In line with the developmental origins of heath and disease (DOHaD) concept, we hope to identify factors in early life where possible intervention can be instituted to prevent the development of NAFLD later in life.

Research objectives

To review the early developmental factors associated with NAFLD and potentially identify areas where intervention can be made to halt the progress to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma which may develop later in life.

Research methods

Original research studies that included risk factors associated with early development of NAFLD in human subjects were identified from databases MEDLINE via PubMed, and EMBASE and relevant publications up to April 30, 2021 were assessed.

Research results

Genetic polymorphisms, familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD.

Research conclusions

Our systematic review summarizes the current available literature on early developmental factors associated with hepatic steatosis. Maternal in utero environment, breastfeeding and nutritional, physical and genetic factors are associated with NAFLD.

Research perspectives

Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas where research and interventions can be explored to prevent the development of NAFLD. Studied in lean individuals with NAFLD are needed and would help to identify risk factors without the confounder of BMI.