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

Kamil Litwinowicz,Ewa Waszczuk,Andrzej Gamian

doi:10.3390/nu13103370

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.

Highlights

Chronic liver diseases account for over 2% of the global total deaths [1]
Due to significant clinical heterogeneity and a low number of obtained papers, we did not attempt to perform meta-analytical synthesis of data regarding the diagnostic accuracy of advanced glycation end-products (AGEs), which is instead presented as narrative synthesis
The results of our study show that chronic liver diseases are associated with elevated concentrations of some fractions of AGEs

Summary

Introduction

Chronic liver diseases account for over 2% of the global total deaths [1]. The percentage contribution of different etiologies is constantly shifting, with non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) increasing in incidence worldwide.NAFLD is estimated to affect 24% of the global population and is currently one of the main causes of the increase in the incidence of cirrhosis [2]. Chronic liver diseases account for over 2% of the global total deaths [1]. The percentage contribution of different etiologies is constantly shifting, with non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) increasing in incidence worldwide. NAFLD is estimated to affect 24% of the global population and is currently one of the main causes of the increase in the incidence of cirrhosis [2]. ALD is responsible for 27% of deaths related to liver disease and 30% of cases of liver cancer worldwide [3]. NAFLD is defined as the presence of at least 5% hepatic steatosis in biopsy specimens. It includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)

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Results

Conclusion