Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
J Gastroenterol. 2010 Jul;45(7):750-7. doi: 10.1007/s00535-010-0203-y. Epub 2010 Jan 30.
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.
晚期糖基化终末产物（AGEs）是蛋白质与糖结合的最终反应产物，已知其可导致多种疾病，包括糖尿病、衰老和神经退行性疾病。最近，我们报告了非酒精性脂肪性肝炎（NASH）患者血清 AGEs 水平升高；此外，我们发现 AGEs 诱导活性氧的产生，继而促进肝星状细胞的增殖和激活，后者是肝纤维化的主要贡献者。在这项研究中，为了探索 AGEs 作为 NASH 缓解的生物标志物的临床用途，我们研究了用降脂药治疗 NASH 是否可以降低血清 AGEs 水平。
本研究纳入了 43 例经活检证实的伴血脂异常的 NASH 患者。在阿托伐他汀（10 mg/日）为期 12 个月的开放标签研究期间，定期进行血清甘油醛衍生的 AGE 测量和临床实验室检查。在治疗期间继续进行标准减重咨询。在治疗前后进行口服葡萄糖耐量试验和计算机断层扫描评估肝脏密度。对 22 例患者进行了随访肝活检。
所有 43 例患者均有血脂异常。治疗期间体重指数和血清葡萄糖水平没有变化。治疗后，NASH 相关代谢参数显著改善。血清甘油醛衍生的 AGE 水平显著降低（分别为 10.4±3.8 和 2.5±1.1 IU/mL）。脂肪变性程度和非酒精性脂肪性肝病（NAFLD）活动评分显著改善。
本研究数据表明，阿托伐他汀可降低血脂异常 NASH 患者的血清 AGEs 水平，并提示 AGEs 作为 NASH 缓解的生物标志物具有一定的临床应用价值。
