Open AccessPathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways
Author(s) -
Ryan B. Perumpail,
Andy Liu,
Robert J. Wong,
Aijaz Ahmed,
Stephen A. Harrison
Publication year - 2015
Publication title -
world journal of hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.913
H-Index - 55
ISSN - 1948-5182
DOI - 10.4254/wjh.v7.i22.2384
Subject(s) - medicine , nonalcoholic fatty liver disease , cirrhosis , hepatocellular carcinoma , adiponectin , metabolic syndrome , fatty liver , pathogenesis , steatosis , insulin resistance , gastroenterology , resistin , chronic liver disease , disease , insulin , obesity
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.