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
Abstract
BACKGROUND

The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.

AIM

To review the early developmental factors associated with NAFLD.

METHODS

Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically.

RESULTS

Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. 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. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.

CONCLUSION

Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.

Keywords: Epidemiology; Natural history; Obesity; Fatty liver; Developmental

Core Tip: 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. The aim of this study is 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.