Published online Aug 7, 2021. doi: 10.3748/wjg.v27.i29.4913
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
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.
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.
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.
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.
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.
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.
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.