Chronic inflammation as a molecular basis of nonalcoholic steatohepatitis: role of macrophages and fibroblasts in the liver

The pathological spectrum of nonalcoholic fatty liver disease includes simple steatosis and nonalcoholic steatohepatitis (NASH), the latter of which is the leading cause of cirrhosis and hepatocellular carcinoma. The available evidence shows that parenchymal cell injury and death trigger inflammation and tissue fibrosis. During the development of liver fibrosis, stromal cells dramatically changes in their cellular component and activation status responding to hepatocyte injury due to various etiologies. It is important to understand how cell death induces chronic inflammation and fibrosis, and the disease-specific macrophages and fibroblasts responsible for NASH development under metabolic stress. This review discusses recent progress in the understanding the pathogenesis of NASH, focusing on disease-specific macrophages and fibroblasts.