The immunopathogenesis of alcoholic and nonalcoholic steatohepatitis: two triggers for one disease?

Alcoholic liver disease and nonalcoholic liver disease represent a leading cause of liver disease and share similar pathogenic mechanisms among which activation of the immune system plays a key role. The main events consist in (a) activation of Kupffer cells via TLR-4 by LPS and fatty acids (b) complement activation (c) increased release of proinflammatory mediators (d) alteration in NK and NKT cell number/activity (e) activation of the adaptive immune system. At the same time, activation of intracellular pro-inflammatory pathways by cytokines and bacterial products, inhibit insulin signaling favoring lipogenesis, metabolic alterations, and cell damage.