Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH
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- Kimura, Y., Hyogo, H., Yamagishi, S. et al. J Gastroenterol (2010) 45: 750. doi:10.1007/s00535-010-0203-y
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Advanced glycation endproducts (AGEs), final reaction products of protein with sugars, are known to contribute to various disorders, including diabetes, aspects of aging, and neurodegenerative diseases. Recently, we reported elevated levels of serum AGEs in patients with nonalcoholic steatohepatitis (NASH); further, we found that AGEs induced the generation of reactive oxygen species followed by the proliferation and activation of hepatic stellate cells, a major contributor to liver fibrosis. In this study, to explore the clinical usefulness of AGEs as a biomarker for the attenuation of NASH, we investigated whether the treatment of NASH with dyslipidemia could decrease serum levels of AGEs.
This study included 43 patients with biopsy-proven NASH with dyslipidemia. Serum glyceraldehyde-derived AGE measurements and clinical laboratory tests were performed periodically during an open-label study of atorvastatin (10 mg daily) for 12 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance tests and liver density assessment by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 22 patients.
All 43 patients had dyslipidemia. The body mass indexes and serum glucose levels did not change during the treatment. After the treatment, NASH-related metabolic parameters were significantly improved. Serum glyceraldehyde-derived AGE levels were significantly decreased (10.4 ± 3.8 and 2.5 ± 1.1 IU/mL before and after treatment, respectively). The steatosis grade and nonalcoholic fatty liver disease (NAFLD) activity score were significantly improved.
The present data demonstrated that atorvastatin decreased the serum levels of AGEs in NASH patients with dyslipidemia and suggest the usefulness of AGEs as a biomarker for the attenuation of NASH.
KeywordsNASH with dyslipidemia Atorvastatin Advanced glycation endproducts Biomarker
Nonalcoholic fatty liver disease
Glyceraldehyde-derived advanced glycation endproducts
Advanced glycation endproducts
Receptor for AGEs
Reactive oxygen species
Thiobarbituric acid reactive substances
Oral glucose tolerance test
Impaired glucose tolerance
Homeostasis model-IR: NAS
Impaired glucose tolerance
Body mass index
Tumor necrosis factor-α
Free fatty acid
Procollagen type III propeptide