Hepatic stellate cell activation occurs in nonalcoholic steatohepatitis

Background/Aims: Hepatic stellate cell activation has a major role in the p athogenesis of hepatic fibrosis, considered to constitute part of the heali ng 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. Methodology: Steatosis, hepatocyte damage, inflammation and fibrosis were g raded from 0 to 3+, in liver biopsies from 15 well documented nonalcoholic steatohepatitis and 5 normal controls. Activated hepatic stellate cell acti vation were identified immunohistochemically using a monoclonal antibody ra ised against cytoplasmic alpha -smooth muscle actin, and semiquantitatively graded using a scoring method. Results: 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 stella te cell was higher in the perivenular areas, than in the intermediate zone and portal area, with no significant association between steatosis and alph a -smooth muscle actin-expressing hepatic stellate cell. However, a signifi cant association was found between portal and lobular inflammation and hepa tic stellate cell index, r = 0.72, P = 0.0005 and r = 0.75, P = 0.0002, res pectively. Conclusions: 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 mechanis ms implicated in fibrosis in nonalcoholic steatohepatitis are probably rela ted with inflammation.