Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.
J Gastroenterol. 2010;45(1):95-104. doi: 10.1007/s00535-009-0133-8. Epub 2009 Sep 30.
Steatosis is a histological finding associated with the progression of chronic hepatitis C. The aims of this study were to elucidate risk factors associated with steatosis and to evaluate the association between steatosis and hepatic expression of genes regulating lipid metabolism.
We analyzed 297 Japanese patients infected with hepatitis C virus and a subgroup of 100 patients who lack metabolic factors for steatosis. We determined intrahepatic mRNA levels of 18 genes regulating lipid metabolism in these 100 patients using real-time reverse transcription-polymerase chain reaction. Levels of peroxisome proliferator-activated receptor alpha and sterol regulatory element-binding protein 1 proteins were assessed by immunohistochemistry.
Steatosis was present in 171 (57%) of 297 patients. The presence of steatosis was independently associated with a higher body mass index, higher levels of gamma-glutamyl transpeptidase and triglyceride, and a higher fibrosis stage. Steatosis was present in 43 (43%) of 100 patients lacking metabolic factors. Levels of mRNA and protein of peroxisome proliferator-activated receptor alpha, which regulates beta-oxidation of fatty acid, were lower in patients with steatosis than in patients without steatosis.
These findings indicate that impaired degradation of lipid may contribute to the development of hepatitis C virus-related steatosis.
脂肪变性是与慢性丙型肝炎进展相关的组织学发现。本研究旨在阐明与脂肪变性相关的危险因素,并评估脂肪变性与调节脂质代谢的基因在肝脏中的表达之间的关系。
我们分析了 297 例日本丙型肝炎病毒感染患者和 100 例无脂肪变性代谢因素的患者亚组。我们使用实时逆转录聚合酶链反应在这 100 例患者中测定了 18 种调节脂质代谢的基因的肝内 mRNA 水平。通过免疫组织化学评估过氧化物酶体增殖物激活受体 α 和固醇调节元件结合蛋白 1 蛋白的水平。
297 例患者中有 171 例(57%)存在脂肪变性。脂肪变性的存在与较高的体重指数、较高的γ-谷氨酰转肽酶和甘油三酯水平以及较高的纤维化分期独立相关。在 100 例无代谢因素的患者中,有 43 例(43%)存在脂肪变性。调节脂肪酸β氧化的过氧化物酶体增殖物激活受体 α 的 mRNA 和蛋白水平在有脂肪变性的患者中低于无脂肪变性的患者。
这些发现表明脂质降解受损可能导致丙型肝炎病毒相关脂肪变性的发生。