Advanced Glycation End-Products in Common Non-Infectious Liver Diseases: Systematic Review and Meta-Analysis

Abstract

Background: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy. Methods: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package. Results: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83–0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78). Conclusions: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH.

Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors

“…Through these, adipose tissue can secrete pro-inflammatory cytokines such as TNFα (Grant and Dixit 2015 ), and it is also able to secrete alarmins such as HMGB1 (Gunasekaran et al 2013 ). AGEs are overexpressed in patients with type 2 diabetes (Vlassara and Striker 2013 ), liver diseases (Litwinowicz et al 2021 ), kidney diseases (Fukami et al 2015 ), and in obese patients (Gaens et al 2013 ). The presence of one or more comorbidities may further increase the already high levels of these proteins, leading to more severe inflammatory symptoms and a decreased response to TNFi.…”

Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH

“…Therefore, among GA-derived AGE structures, only those to which the anti-TAGE antibody binds appear to be cytotoxic. Accordingly, AGEs that bind the anti-TAGE antibody were referred to as toxic AGEs (TAGE) [ 47 , 48 ].…”

An Update on Mechanistic Modes in AGEs Stimulated & ER and Inflammatory Stress-Modulated Control of the GLUT4 expression (SLC2A4 promoted) and Atherogenesis in Diabetes Mellitus-A Narrative Review

“…Apart from the extravasation of AGEs as well as their crosstalk with RAGE has a correlation with formation besides evolution of different chronic diseases inclusive of steatosis along with CVD [119]. A correlation amongst escalated quantities of different kinds of AGEs along with NAFLD was illustrated in a recent meta-analysis [120]. The estimation of fluorescent AGEs has been regarded to be a probable biomarker for stratifying NAFLD [121].…”