Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4103-4110
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4103
Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: An open question
Letiția Adela Maria Streba, Cristin Constantin Vere, Ion Rogoveanu, Costin Teodor Streba
Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania
Cristin Constantin Vere, Ion Rogoveanu, Costin Teodor Streba, Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania
Cristin Constantin Vere, Ion Rogoveanu, Internal Medicine, Gastroenterology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania
Author contributions: Streba LAM, Vere CC, and Rogoveanu I contributed equally to this manuscript and share first authorship; Streba LAM and Vere CC wrote this paper; Rogoveanu I and Streba CT performed the literature search and critically revised the text.
Supported by Grant from European Social Found, Human Resources Development Operational Programme 2007-2013, No. POSDRU/159/1.5/133377.
Conflict-of-interest: The authors have no conflicts of interest to disclose.
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: Costin Teodor Streba, MD, PhD, MSc, Research Center of Gastroenterology and Hepatology of Craiova, University of Medicine and Pharmacyof Craiova, 1 Mai 66, 200639 Craiova, Romania. costinstreba@gmail.com
Telephone: +40-722-389906 Fax: +40-351-401376
Received: November 29, 2014
Peer-review started: November 29, 2014
First decision: December 26, 2014
Revised: January 17, 2015
Accepted: February 13, 2015
Article in press: February 13, 2015
Published online: April 14, 2015
Processing time: 137 Days and 3.2 Hours
Abstract

Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.

Keywords: Diabetes mellitus; Hepatocellular carcinoma; Metabolic syndrome; Non-alcoholic fatty liver disease; Obesity

Core tip: Nonalcoholic liver disease (NAFLD) comprises both simple steatosis or nonalcoholic fatty liver and nonalcoholic steatohepatitis, with or without cirrhosis. Recent data demonstrate a strong association between most features of metabolic syndrome and NAFLD. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, for which current epidemiologic data show an increased incidence in NAFLD patients. Basic research has identified pathways linking obesity, type 2 diabetes, systemic inflammation, NAFLD/nonalcoholic steatohepatitis, and HCC. However, more data are necessary in order to effectively establish these relationships, and perhaps pave the way for possible cures to prevent HCC in certain populations.