title: Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways.
abstract: Although hepatocellular carcinoma (HCC) primarily arises in the background of liver cirrhosis, the development of HCC in nonalcoholic fatty liver disease (NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome (MS) along with obesity and insulin resistance (IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS, NAFLD, and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, leptin and resistin, as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver, which precede HCC development. Nevertheless, further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.
authors.affiliation: Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Perumpail
authors.affiliation: Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Andy
authors.initials: A
authors.lastname: Liu
authors.affiliation: Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wong
authors.affiliation: Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
keywords: Hepatocellular carcinoma; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis