Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 28, 2015; 7(18): 2155-2161
Published online Aug 28, 2015. doi: 10.4254/wjh.v7.i18.2155
Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma
Fauzia Z Khan, Ryan B Perumpail, Robert J Wong, Aijaz Ahmed
Fauzia Z Khan, Ryan B Perumpail, Aijaz Ahmed, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, United States
Robert J Wong, Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital Campus, Oakland, CA 94602, United States
Author contributions: Khan FZ, Perumpail RB, Wong RJ and Ahmed A developed an outline for the review article; Khan FZ, Perumpail RB, Wong RJ and Ahmed A performed research; Khan FZ, Perumpail RB, Wong RJ and Ahmed A performed a medline search to review the published data on this topic; Khan FZ and Perumpail RB prepared the initial and final draft based on input from senior authors; Wong RJ and Ahmed A reviewed each section of the manuscript and provided critical mentorship to complete this review article.
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:
Correspondence to: Aijaz Ahmed, MD, Associate Professor of Medicine, Medical Director Liver Transplant Program, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite 210, Palo Alto, Stanford, CA 94305, United States.
Telephone: +1-650-4986091 Fax: +1-650-4985692
Received: April 24, 2015
Peer-review started: April 24, 2015
First decision: July 17, 2015
Revised: July 22, 2015
Accepted: August 16, 2015
Article in press: August 17, 2015
Published online: August 28, 2015

An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

Keywords: Hepatocellular carcinoma, Nonalcoholic fatty liver disease, Obesity, Insulin resistance, Nonalcoholic steatohepatitis, Overweight

Core tip: The worldwide rise in overweight and obesity has been associated with increasing rates of nonalcoholic fatty liver disease (NAFLD), which is now the most common etiology of chronic liver disease. The more aggressive form of NAFLD, nonalcoholic steatohepatitis (NASH), promotes the development of hepatocellular carcinoma (HCC). As NASH-related cirrhosis has emerged as the most rapidly increasing indication for HCC-related liver transplantation in the United States, new strategies for HCC surveillance and targeted therapies in this patient population are warranted.