Journal of Gastroenterology

, Volume 45, Issue 7, pp 750–757

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

  • Yuki Kimura
  • Hideyuki Hyogo
  • Sho-ichi Yamagishi
  • Masayoshi Takeuchi
  • Tomokazu Ishitobi
  • Yoshitaka Nabeshima
  • Koji Arihiro
  • Kazuaki Chayama
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-010-0203-y

Cite this article as:
Kimura, Y., Hyogo, H., Yamagishi, S. et al. J Gastroenterol (2010) 45: 750. doi:10.1007/s00535-010-0203-y

Abstract

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.

Keywords

NASH with dyslipidemiaAtorvastatinAdvanced glycation endproductsBiomarker

Abbreviations

NASH

Nonalcoholic steatohepatitis

NAFLD

Nonalcoholic fatty liver disease

IR

Insulin resistance

glycer-AGE

Glyceraldehyde-derived advanced glycation endproducts

AGEs

Advanced glycation endproducts

RAGE

Receptor for AGEs

ROS

Reactive oxygen species

TBARS

Thiobarbituric acid reactive substances

OGTT

Oral glucose tolerance test

IGT

Impaired glucose tolerance

DM

Diabetes mellitus

HOMA-IR

Homeostasis model-IR: NAS

NAFLD

Activity score

IGT

Impaired glucose tolerance

BMI

Body mass index

TNF-α

Tumor necrosis factor-α

FFA

Free fatty acid

P-III-P

Procollagen type III propeptide

HMG-CoA

3-Hydroxy-3-methylglutaryl-coenzyme A

Copyright information

© Springer 2010

Authors and Affiliations

  • Yuki Kimura
    • 1
  • Hideyuki Hyogo
    • 1
  • Sho-ichi Yamagishi
    • 2
  • Masayoshi Takeuchi
    • 3
  • Tomokazu Ishitobi
    • 1
  • Yoshitaka Nabeshima
    • 1
  • Koji Arihiro
    • 4
  • Kazuaki Chayama
    • 1
  1. 1.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Pathophysiology and Therapeutics of Diabetic Vascular ComplicationsKurume University School of MedicineKurumeJapan
  3. 3.Department of Pathophysiological Science, Faculty of Pharmaceutical SciencesHokuriku UniversityToyamaJapan
  4. 4.Department of Pathology, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan