Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2016; 22(37): 8294-8303
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8294
Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease
Carrie R Wong, Mindie H Nguyen, Joseph K Lim
Carrie R Wong, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, United States
Mindie H Nguyen, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, United States
Joseph K Lim, Yale Liver Center, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, United States
Author contributions: Wong CR drafted the manuscript, contributed to the conception and design, and made revisions for resubmission; Nguyen MH and Lim JK contributed to the conception and design and provided critical revisions of the manuscript.
Conflict-of-interest statement: There is no conflict of interest associated with any of the authors.
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:
Correspondence to: Joseph K Lim, MD, Associate Professor, Yale Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520, United States.
Telephone: +1-203-7376063 Fax: +1-203-7857273
Received: April 29, 2016
Peer-review started: May 4, 2016
First decision: July 13, 2016
Revised: August 3, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 7, 2016

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma (HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.

Keywords: Fatty liver, Nonalcoholic steatohepatitis, Hepatocellular carcinoma, Liver cirrhosis, Liver cancer

Core tip: This review summarizes the epidemiology, pathogenesis, disease presentation, demand and receipt of curative treatment, and post-treatment outcomes of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD). The review highlights the developing understanding of NAFLD-HCC pathogenesis, which has broadened to include genetic polymorphisms, adaptive immune responses, and cellular regenerative pathways using hepatic progenitor cell populations. While NAFLD-HCC has been described to have poorer prognosis as compared with other HCC etiologies, this review features summarized evidence that disease-free and survival rates among patients with NAFLD-HCC are comparable and potentially favorable after receipt of curative treatment.