Chronic Inflammation in Non-Alcoholic Steatohepatitis: Molecular Mechanisms and Therapeutic Strategies

Figure 1. Hepatic complications associated with obesity. The NAFLD development and progression are influenced by environmental, genetic, and individual features. The main predictors of disease progression are the presence of type II diabetes, metabolic syndrome, hypertension, and dysbiosis. NAFLD progression is also influenced by genetic, epigenetic, gender, and age components. The dysregulation of extra-hepatic organ functions such as adipose tissue, gut, and muscle, as well as intra-hepatic events (inflammation, cell death, cellular stresses), have been reported in NAFLD. Cardiovascular disease (25–43%) is the primary cause of death in NAFLD patients, while liver-related disease (9–15%) is also substantial. NAFL, non-alcoholic fatty liver; NAFLD, non-alcoholic fatty liver diseases; NASH, non-alcoholic steatohepatitis.

Figure 2. Cellular interplay during chronic liver diseases. Liver resident and recruited immune cells, stressed hepatocytes and liver sinusoidal endothelial cells contribute to development of the chronic inflammation associated with NAFLD. Inflammatory mediators reaching the liver are key contributors of disease progression as they influence hepatic cell functions. Full arrow, confirmed effect; dotted arrow, putative effect.

Figure 3. Therapeutic targets at different stages of liver complications. Main molecules targeting metabolic and inflammatory mediators expressed during the progression of liver complications of obesity are listed with some of which are currently in clinical evaluation.