Reply to the letter by Y. Yilmaz regarding ‘‘the AGEs–RAGE axis and nonalcoholic steatohepatitis’’

Abstract

We appreciate the interest shown by Dr. Yusuf Yilmaz in his recent letter as well as his comments. As he pointed out, the AGEs–RAGE axis is emerging as a core piece in the pathophysiology of insulin resistance, NAFLD and NASH. We have therefore analyzed the serum levels of circulating soluble isoforms of RAGE (sRAGE) in NASH patients with metabolic disorders before and during their treatments. We have found that decreased levels of sRAGE prior to treatment initiation were correlated with deteriorated post-treatment histological findings and that sRAGE levels appeared to have increased after the treatments (data not published). Based on our data, we suggest that not only atorvastatin treatment but also other successful treatments could increase the serum levels of sRAGE. Yilmaz et al. have examined the relationship between circulating levels of sRAGE and NAFLD in humans and demonstrated that levels of sRAGE are highly reduced in the setting of NASH and inversely correlated with ALT and AST levels. Our results will support these findings. In our paper on the effects of atorvastatin treatment on serum levels of AGEs in NASH patients with dyslipidemia, our first priority was to show the important aspects of serum AGEs as a marker for oxidative stress as well for the diabetic condition. As such, we will provide data on the relationship between sRAGE and AGEs before and during the various treatments based upon the AGEs–RAGE axis theory in the future.