title: Pathogenesis of nonalcoholic steatohepatitis.
abstract: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease and a risk factor for cirrhosis and hepatocellular carcinoma. The pathological features of NASH include steatosis, hepatocyte injury, inflammation, and various degrees of fibrosis. Steatosis reflects disordered lipid metabolism. Insulin resistance and excessive fatty acid influx to the liver are two important contributing factors. Steatosis is also likely associated with lipotoxicity and cellular stresses such as oxidative stress and endoplasmic reticulum stress, which result in hepatocyte injury. Inflammation and fibrosis are frequently triggered by various signals such as proinflammatory cytokines and chemokines, released by injuried hepatocytes and activated Kupffer cells. Although much progress has been made, the pathogenesis of NASH is not fully elucidated. The purpose of this review is to discuss the current understanding of NASH pathogenesis, mainly focusing on factors contributing to steatosis, hepatocyte injury, inflammation, and fibrosis.
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, The State University of New York at Buffalo (SUNY Buffalo), 3435 Main Street, 422 BRB, Buffalo, NY, 14214, USA. wl11@buffalo.edu.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, The State University of New York at Buffalo (SUNY Buffalo), 3435 Main Street, 422 BRB, Buffalo, NY, 14214, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, The State University of New York at Buffalo (SUNY Buffalo), 3435 Main Street, 422 BRB, Buffalo, NY, 14214, USA.
authors.forename: Tavleen
authors.initials: T
authors.lastname: Bhatia
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, The State University of New York at Buffalo (SUNY Buffalo), 3435 Main Street, 422 BRB, Buffalo, NY, 14214, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, The State University of New York at Buffalo (SUNY Buffalo), 3435 Main Street, 422 BRB, Buffalo, NY, 14214, USA. sbaker@upa.chob.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D000069196:Gastrointestinal Microbiome; D020022:Genetic Predisposition to Disease; D055166:Hepatic Stellate Cells / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D007728:Kupffer Cells / Q000473:pathology; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008099:Liver / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000503:physiopathology* / Q000628:therapy; D018384:Oxidative Stress; D012307:Risk Factors; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D005227:Fatty Acids; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta
keywords: Apoptosis; Autophagy; Genetic predisposition; Gut microbiota; Hepatic stellate cells