Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C
Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C
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DOI：
10.1111/j.1478-3231.2007.01608.x
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发表时间：
2008-03-01
影响因子：
6.7
通讯作者：
Dufour, Jean-Francois
中科院分区：
文献类型：
--
作者：
Hora, Caroline;Negro, Francesco;Dufour, Jean-Francois
背景/目的：脂肪变性和胰岛素抵抗均与慢性丙型肝炎纤维化加速有关。结缔组织生长因子（CTGF）在包括肝硬化在内的纤维化疾病的细胞外基质生成中起重要作用，其在体外受胰岛素和葡萄糖刺激表达。我们假设CTGF可能与脂肪变性、胰岛素抵抗和纤维化有关。方法：我们纳入了153名慢性丙型肝炎患者，他们参加了瑞士丙型肝炎队列研究，并进行了肝活检和血浆样本。免疫组织化学定量检测CTGF表达。94例患者（57例基因型为非3型）的血浆葡萄糖、胰岛素和瘦素水平也被测量。免疫印迹法检测LX-2星状细胞CTGF的合成。结果：结缔组织生长因子在脂肪变性患者（P = 0.039）和纤维化患者（P = 0.008）中的表达高于无这些特征的患者。CTGF水平与胰岛素血症或血糖无关，也与炎症无关。通过多元回归分析，CTGF水平与脂肪变性、酗酒史、血浆瘦素和HCV RNA水平独立相关；当仅考虑非3基因型患者时，CTGF水平与既往酒精滥用史、血浆瘦素水平和脂肪变性独立相关。瘦素刺激LX-2细胞的CTGF合成。结论：在慢性丙型肝炎和脂肪变性患者中，CTGF可能独立于炎症促进纤维化。CTGF可能通过增加瘦素水平将脂肪变性和纤维化联系起来。
Background/Aim: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor ( CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. Methods: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. Results: Connective tissue growth factor expression was higher in patients with steatosis (P = 0.039) and in patients with fibrosis (P = 0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. Conclusions: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.