Key molecular pathways in the progression of non-alcoholic steatohepatitis.

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and also become an emerging risk factor for liver-related complications, such as cirrhosis and hepatocellular carcinoma (HCC). The liver-related burden of NASH is likely to increase and nonalcoholic steatohepatitis (NASH) is probably to be the leading indication for liver transplantation by 2020, as a consequence of increased disease prevalence and of the lack of an effective treatment. The first step in the NAFLD development is represented by fat accumulation in the liver, a condition that is commonly associated with features of the metabolic syndrome. Notably, it has been acknowledged that the step from nonalcoholic fatty liver (NAFL) to NASH is key step in the NASH formation, and the mechanisms behind this transition have been extensively studied. Emerging evidence indicates that innate immunity is a driving force in NAFLD progression because it directly regulates all key pathogenic features of the disease processes, including metabolic dysregulation, inflammation, and fibrosis. In this review, we summarize the currently available signaling pathways of NASH formation, including oxidative stress, NOD-like receptors (NLRs), mitochondria-associated pathways, Toll-like receptors (TLRs), nuclear receptors, and other signal pathways, for the aim of a better understanding of this disease.