Neovascularization and oxidative stress in the progression of non-alcoholic steatohepatitis

Reactive oxygen species (ROS) is known to play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH); however, as we previously reported, angiogenesis also plays a pivotal role in NASH progression - the development of liver fibrosis and hepatocellular carcinoma - in rats. The aim of the current study was to elucidate the role of angiogenesis in the development of fibrosis in NASH. Twenty-six patients with NASH and 11 with simple fatty liver (FL) disease were enrolled in the study and underwent clinicopathological examination. Immunohistochemical analysis of 4-hydroxy-2-noneal (4-HNE) and CD34 was employed for the detection of ROS and angiogenesis in the liver tissues, respectively. Both the NASH and FL samples displayed a marked staining of 4-HNE as compared to the healthy liver. Similar levels of 4-HNE were observed in NASH regardless of the grade of liver fibrosis. In sharp contrast, hepatic neovascularization developed significantly in NASH alone, whereas almost no neovascularization was observed in FL or the healthy liver. The degree of angiogenesis was almost parallel with the development of liver fibrosis. In conclusion, simple FL and NASH cases were both affected by ROS. However, only NASH was associated with marked neovascularization, proportional to the increase in the grade of liver fibrosis development. These results indicate that hepatic neovascularization may play an important role in the onset and progression of NASH.