NASH and the Cross-Talk Between the Gut and Liver

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases of the liver, even in pediatrics. NAFLD ranges from simple fat accumulation (steatosis) to inflammation and fibrosis [nonalcoholic steatohepatitis (NASH)]. The progression of disease is a critical aspect, since the evolution of fatty liver to fibrotic stages may be the prelude to cirrhosis and hepatocellular carcinoma. Accumulating evidence has shown that the connection between the gut and the liver is crucial among the factors involved in liver disease progression. In patients with NAFLD, small bowel bacterial overgrowth and an increased intestinal permeability are present. In such conditions, the hepatobiliary system is inevitably exposed to a high level of bacterial products and is thus able to activate the innate immune system and initiate the cascade of proinflammatory signal transduction leading to liver inflammation and fibrosis. This review will provide an overview of the current knowledge on the pathophysiology of the cross-talk between the gut and the liver in the pathogenesis of NAFLD and its progression to NASH, and will discusses potential therapeutic means to manipulate the intestinal microbiota in order to modulate liver disease development. © 2014, Springer Science + Business Media New York.