In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH HM781-36B and NASH have disease-specific mechanisms and therefore represent distinct biological entities. Further studies are needed to dissect the emerging differences in pathogenesis of these two conditions. Liver diseases represent a significant cause of morbidity and mortality worldwide, ranking

as the ninth leading cause of death.[1-3] Only second to viral hepatitis, alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD) represent the most prevalent liver diseases in the United States and developed countries.[4-6] Both entities have a broad clinical spectrum, ranging from simple steatosis to steatohepatitis with or without fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis, observed in simple ALD and

in NAFLD is a benign and self-limited condition, but in 10–20% cases, the condition progresses to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH), which share a component of liver inflammation and injury mediated by the innate immune response.[7] This is of a clinical importance 上海皓元 because inflammation determines the long-term prognosis of patients with these selleckchem diseases,

whereas steatosis per se does not appear to have an adverse impact on long-term outcome.[8-11] The concept of dysregulated innate immunity as an indispensable component of ASH and NASH is supported by the findings that patients with ASH have increased antibodies against Escherichia coli in plasma,[12] patients with NASH have increased serum antibodies against endotoxin,[13] and that consumption of alcohol or intake of a high-fat or high-carbohydrate diet leads to an increase in gut-derived endotoxin in the portal circulation, activating resident liver macrophages to produce several pro-inflammatory cytokines.[14-18] Recognition of Toll-like receptors (TLR) as the key components involved in activation of the innate immune system enabled substantial progress in understanding the mechanisms mediating ASH and NASH. Due to its unique blood supply via the portal system, the liver receives blood from the intestine, exposing hepatocytes and liver immune cells not only to nutrients but also to gut-derived microbial products, including the lipopolysaccharide (LPS, endotoxin), a component of Gram-negative bacterial wall.[19] Multiple lines of evidence support the hypothesis that gut-derived endotoxin is involved in ASH and NASH.