Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2021; 27(29): 4913-4928
Published online Aug 7, 2021. doi: 10.3748/wjg.v27.i29.4913
Advanced glycation end product: A potential biomarker for risk stratification of non-alcoholic fatty liver disease in ELSA-Brasil study
Evelyn Nunes Goulart da Silva Pereira, Daniela Polessa Paula, Beatriz Peres de Araujo, Maria de Jesus Mendes da Fonseca, Maria de Fátima Haueisen Sander Diniz, Anissa Daliry, Rosane Harter Griep
Evelyn Nunes Goulart da Silva Pereira, Beatriz Peres de Araujo, Anissa Daliry, Laboratory of Cardiovascular Investigation, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil
Daniela Polessa Paula, National School of Statistical Sciences, Brazilian Institute of Geography and Statistics, Rio de Janeiro 20231-050, Brazil
Maria de Jesus Mendes da Fonseca, Department of Epidemiology and Quantitative Methods in Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil
Maria de Fátima Haueisen Sander Diniz, Faculty of Medicine, Universidade Federal de Minas Gerais, Minas Gerais 31270-901, Brazil
Rosane Harter Griep, Laboratory of Health and Environment Education, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil
Author contributions: Pereira ENGDS and Araujo BP collected and analyzed the data, drafted the manuscript and revised the manuscript; Paula DP analyzed the data and revised the manuscript; Fonseca MJMD and Griep RH collected the data and revised the manuscript; Diniz MFHS revised the manuscript; Daliry A designed the study, collected and analyzed the data, drafted the manuscript and revised the manuscript; all authors approved the final version of the manuscript prior to submission.
Supported by Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science and Technology (Financiadora de Estudos e Projetos and CNPq National Research Council), No. 01 06 0010.00 RS, No. 01 06 0300.00 ES, No. 01 06 0212.00 BA, No. 01 06 0278.00 MG, No. 01 06 0115.00 SP, and No. 01 06 0071.00 RJ; and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Carlos Chagas Filho Rio de Janeiro State Research Support Foundation (FAPERJ) (to Griep RH).
Institutional review board statement: The study was reviewed and approved for publication by Oswaldo Cruz Institute, Oswaldo Cruz Foundation.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflict of interests to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anissa Daliry, MSc, PhD, Academic Research, Laboratory of Cardiovascular Investigation, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro 21040-360, Brazil. daliry@ioc.fiocruz.br
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: March 7, 2021
Revised: March 18, 2021
Accepted: April 26, 2021
Article in press: April 26, 2021
Published online: August 7, 2021
Processing time: 188 Days and 6.8 Hours
ARTICLE HIGHLIGHTS
Research background

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and it affects about 25% of the adult population, and can progress to hepatocellular carcinoma, death, and/or liver transplantation. The underlying mechanisms that account for disease progression are still not fully understood due to its complexity.

Research motivation

Liver diseases are associated with the excess formation of advanced glycation end products (AGEs), which induce tissue inflammation and oxidative damage. However, the trend of oxidative marker levels according to NAFLD severity is unclear.

Research objectives

We aim to understand whether NAFLD-associated steatosis severity was associated with serum AGE levels in the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study to address the specific pathophysiological mechanisms underlying NAFLD association with AGEs in a large and mixed population cohort.

Research methods

NAFLD-associated steatosis severity was classified by ultrasound hepatic attenuation: mild and moderate/severe pooled. The measurement of serum fluorescent AGE concentrations was based on spectrofluorimetric detection. Serum AGE content and clinical and laboratory characteristics of the participants were compared between groups. The correlation between serum AGE levels and the grade of steatosis was analyzed. Logistic regression analysis was used to investigate the relationship between serum AGE levels and NAFLD-associated steatosis severity. A P value < 0.05 was considered statistically significant.

Research results

According to hepatic steatosis grade in NAFLD, from mild to moderate/severe, individuals with the most severe forms of steatosis had a higher incidence of metabolic syndrome, diabetes mellitus, and high cholesterol levels. Moreover, individuals with increasing severity of NAFLD-associated steatosis presented increasing waist circumference, body mass index, systolic and diastolic blood pressure, fasting blood glucose, glycated hemoglobin, insulin, triglycerides, alanine aminotransferase, gamma-glutamyl transferase, C-reactive protein, and uric acid levels and lower high-density lipoprotein. Higher serum AGE content was present in the moderate/severe group of individuals than in the mild group. In addition, the serum AGE levels were correlated with the steatosis grade in the overall sample. Logistic regression analysis, after adjusting for confounding variables, showed that subjects with higher serum AGE content had a 4.6-fold increased chance of having moderate or severe forms of NAFLD-associated steatosis when compared to low levels of serum AGEs.

Research conclusions

Steatosis severity in NAFLD patients was associated with serum AGE levels, thereafter AGEs could be a good marker of NAFLD stratification accordingly to steatosis grade, strengthening the involvement of AGE in NAFLD pathogenesis.

Research perspectives

Plasmatic fluorescent AGE quantification by spectroscopy could be a promising alternative method to monitor progression from mild to severe forms of NAFLD accordingly to the severity of hepatic steatosis.