Журнал клинической и клеточной иммунологии
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ISSN: 2155-9899
ISSN: 2155-9899
Sergio Cerpa-Cruz, Veronica Gonzalez-Diaz, Gloria Martinez-Bonilla, Sergio Gutierrez-Urena, Elsa Rodriguez-Cortes, Lizbeth A. Garcia-Espinosa, Miguel A Martinez-Valles and J Antonio Velarde-Ruiz-Velazco
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease in the United States. Non-alcoholic steatohepatitis (NASH), the most severe form of NAFLD, has an increased risk for progression to cirrhosis and associated comorbidities such as cardiovascular disease. Metabolic syndrome (MS) including insulin resistance and obesity is central to the development of NASH. It is now estimated to affect 30% of adults and about 10% of children in the U.S. Hispanics are disproportionably affected with not only higher rates of NAFLD but also more severe disease. Emerging data indicate that NASH progression results from parallel events originating from the liver as well as from the adipose tissue, the gut and the gastrointestinal tract. Thus, dysfunction of the adipose tissue through enhanced flow of free fatty acids and release of adipocytokines, and alterations in the gut microbiome generate pro-inflammatory signals that increase NASH progression. Additional ‘extrahepatic hits’ include dietary factors and gastrointestinal hormones. Within the liver, hepatocyte apoptosis, ER stress and oxidative stress are key contributors to hepatocellular injury. In addition, lipotoxic mediators and danger signals activate Kupffer cells which initiate and perpetuate the inflammatory response by releasing inflammatory mediators that contribute to inflammatory cell recruitment and development of fibrosis. Inflammatory and fibrogenic mediators include chemokines, the inflammasome and activation of pattern-recognition receptors.