Cortez-Pinto H, Baptista A, Camilo M E, de Moura M C
Department of Medicine 2, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1669, Lisboa, Portugal.
Hepatogastroenterology. 2001 Jan-Feb;48(37):87-90.
BACKGROUND/AIMS: Hepatic stellate cell activation has a major role in the pathogenesis of hepatic fibrosis, considered to constitute part of the healing response to a necroinflammatory stimulus. However, steatosis per se, has also been shown to induce this activation. This study evaluates if hepatic stellate cell activation is present, and how it correlates with steatosis, in nonalcoholic steatohepatitis, whose hallmark is steatosis.
Steatosis, hepatocyte damage, inflammation and fibrosis were graded from 0 to 3+, in liver biopsies from 15 well documented nonalcoholic steatohepatitis and 5 normal controls. Activated hepatic stellate cell activation were identified immunohistochemically using a monoclonal antibody raised against cytoplasmic alpha-smooth muscle actin, and semiquantitatively graded using a scoring method.
Nonalcoholic steatohepatitis patients showed significantly greater numbers of alpha-smooth muscle actin-reactive hepatic stellate cell than controls: hepatic stellate cell index of 3.6 +/- 1.9 versus 1.5 +/- 0.5, P < 0.05. The distribution of alpha-smooth muscle actin-reactive hepatic stellate cell was higher in the perivenular areas, than in the intermediate zone and portal area, with no significant association between steatosis and alpha-smooth muscle actin-expressing hepatic stellate cell. However, a significant association was found between portal and lobular inflammation and hepatic stellate cell index, r = 0.72, P = 0.0005 and r = 0.75, P = 0.0002, respectively.
This study demonstrates that hepatic stellate cell activation occurs in nonalcoholic steatohepatitis, clearly correlating with portal and lobular inflammation, but not with steatosis, suggesting that the mechanisms implicated in fibrosis in nonalcoholic steatohepatitis are probably related with inflammation.
背景/目的：肝星状细胞激活在肝纤维化发病机制中起主要作用，被认为是对坏死性炎症刺激的愈合反应的一部分。然而，脂肪变性本身也已被证明可诱导这种激活。本研究评估在以脂肪变性为特征的非酒精性脂肪性肝炎中是否存在肝星状细胞激活，以及它与脂肪变性如何相关。
对15例有充分记录的非酒精性脂肪性肝炎患者和5例正常对照的肝活检组织中，脂肪变性、肝细胞损伤、炎症和纤维化进行0至3+分级。使用针对细胞质α-平滑肌肌动蛋白的单克隆抗体通过免疫组织化学鉴定活化的肝星状细胞，并使用评分方法进行半定量分级。
非酒精性脂肪性肝炎患者中α-平滑肌肌动蛋白反应性肝星状细胞数量明显多于对照组：肝星状细胞指数为3.6±1.9 vs 1.5±0.5，P<0.05。α-平滑肌肌动蛋白反应性肝星状细胞在小叶静脉周围区域的分布高于中间带和门管区，脂肪变性与表达α-平滑肌肌动蛋白的肝星状细胞之间无显著关联。然而，分别在门管区和小叶炎症与肝星状细胞指数之间发现显著关联，r = 0.72，P = 0.0005和r = 0.75，P = 0.0002。
本研究表明非酒精性脂肪性肝炎中发生肝星状细胞激活，与门管区和小叶炎症明显相关，但与脂肪变性无关，提示非酒精性脂肪性肝炎中涉及纤维化的机制可能与炎症有关。
