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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kimura
Yuki
Y
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
Hyogo
Hideyuki
H
Yamagishi
Sho-ichi
S
Takeuchi
Masayoshi
M
Ishitobi
Tomokazu
T
Nabeshima
Yoshitaka
Y
Arihiro
Koji
K
Chayama
Kazuaki
K
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000097:blood*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods; D055815:Young Adult
D000924:Anticholesteremic Agents; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D006538:Heptanoic Acids; D011758:Pyrroles; D017382:Reactive Oxygen Species; D000069059:Atorvastatin