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
Abstract
BACKGROUND

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 the steatosis grade in non-alcoholic fatty liver disease (NAFLD) is unclear.

AIM

To compare serum AGE levels between participants with NAFLD accordingly to steatosis severity in the baseline ELSA-Brasil population.

METHODS

In 305 individuals at baseline ELSA-Brasil, NAFLD-associated steatosis was classified by ultrasound hepatic attenuation. The participants were grouped according to the severity of steatosis: 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 steatosis severity. A P value < 0.05 was considered statistically significant.

RESULTS

According to the steatosis severity spectrum in NAFLD, from mild to moderate/severe, individuals with the most severe steatosis grade had a higher incidence of metabolic syndrome (63% vs 34%, P ≤ 0.001), diabetes mellitus (37% vs 14%, P ≤ 0.001), and high cholesterol levels (51% vs 33%, P < 0.001). Moreover, individuals with increasing severity of 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 (P = 0.008). In addition, the serum AGE levels were correlated with the steatosis grade in the overall sample (rho = 0.146, P = 0.010). 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 steatosis when compared to low levels of serum AGEs. According to the results of the receiver operator characteristic curves analyses (areas under the curve, AUC = 0.83), AGEs could be a good marker of steatosis severity in patients with NAFLD and might be a potential biomarker in predicting NAFLD progression, strengthening the involvement of AGE in NAFLD pathogenesis.

CONCLUSION

NAFLD-associated steatosis was associated with serum AGE levels; therefore, plasmatic fluorescent AGE quantification by spectroscopy could be a promising alternative method to monitor progression from mild to severe NAFLD accordingly to steatosis grade.

Keywords: Advanced glycation end products; Non-alcoholic fatty liver disease; Steatosis; ELSA-Brasil study; Spectroscopy

Core Tip: We evaluated the relationship between fluorescent advanced glycation end product (AGE) levels and the severity of non-alcoholic fatty liver disease (NAFLD)-associated steatosis. We evaluated 305 subjects with NAFLD from Rio de Janeiro in the baseline ELSA-Brasil population grouped according to the steatosis stratification: mild and moderate/severe pooled. Serum AGE levels were correlated with the steatosis grade in the overall sample. The severity of NAFLD-associated steatosis was associated with serum AGE levels; therefore, plasmatic fluorescent AGE quantification by spectroscopy could be a promising alternative method for classifying and grading NAFLD accordingly to hepatic steatosis.