Perumpail RB, Liu A, Wong RJ, Ahmed A, Harrison SA. Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways. World J Hepatol 2015; 7(22): 2384-2388 [PMID: 26464753 DOI: 10.4254/wjh.v7.i22.2384]
Corresponding Author of This Article
Aijaz Ahmed, MD, Associate Professor of Medicine, Medical Director of Liver Transplant Program, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, 750 Welch Road, Suite 210, Stanford, CA 94305, United States. aijazahmed@stanford.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Oct 8, 2015; 7(22): 2384-2388 Published online Oct 8, 2015. doi: 10.4254/wjh.v7.i22.2384
Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways
Ryan B Perumpail, Andy Liu, Robert J Wong, Aijaz Ahmed, Stephen A Harrison
Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, Stanford, CA 94305, United States
Andy Liu, Albert Einstein College of Medicine, Bronx, NY 10461, United States
Robert J Wong, Division of Gastroenterology and Hepatology, Alameda Health System, Highland Hospital Campus, Oakland, CA 94602, United States
Stephen A Harrison, Division of Gastroenterology, San Antonio Military Medical Center, Fort Sam, Houston, TX 78234, United States
Author contributions: Perumpail RB prepared first and final draft, revised the final draft based on feedback from other authors; Liu A, Wong RJ, Ahmed A and Harrison SA reviewed and revised each segment of the document and checked references for completeness.
Conflict-of-interest statement: We declare that we have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Aijaz Ahmed, MD, Associate Professor of Medicine, Medical Director of Liver Transplant Program, Division of Gastroenterology and Hepatology, Liver Transplant Program, Stanford University School of Medicine, 750 Welch Road, Suite 210, Stanford, CA 94305, United States. aijazahmed@stanford.edu
Telephone: +1-650-4986091 Fax: +1-650-4985692
Received: May 23, 2015 Peer-review started: May 26, 2015 First decision: August 14, 2015 Revised: September 1, 2015 Accepted: September 10, 2015 Article in press: September 16, 2015 Published online: October 8, 2015 Processing time: 132 Days and 0.8 Hours
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.
Core tip: 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 along with obesity and insulin resistance underlie several unique mechanisms that promote tumorigenesis.
