Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2022; 28(3): 310-331
Published online Jan 21, 2022. doi: 10.3748/wjg.v28.i3.310
Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link
Lampros Chrysavgis, Ilias Giannakodimos, Panagiota Diamantopoulou, Evangelos Cholongitas
Lampros Chrysavgis, Department of Experimental Physiology, National and Kapodistrian University of Athens, Athens 11527, Greece
Ilias Giannakodimos, Panagiota Diamantopoulou, Evangelos Cholongitas, First Department of Internal Medicine, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Chrysavgis L performed the investigation, conceptualization, writing-original draft, visualization; Giannakodimos I and Diamantopoulou P contributed to the writing-original draft, and validation; Cholongitas E performed the resources, writing-review and editing, supervision, project administration; all authors have read and agreed to the final version of the manuscript.
Conflict-of-interest statement: The authors have nothing to disclose related to the manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Evangelos Cholongitas, MD, PhD, Associate Professor, First Department of Internal Medicine, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Agiou Thoma 17, Athens 11527, Greece.
Received: September 9, 2021
Peer-review started: September 9, 2021
First decision: October 16, 2021
Revised: October 19, 2021
Accepted: January 6, 2022
Article in press: January 6, 2022
Published online: January 21, 2022

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus. Although it is considered a benign disease, NAFLD can progress to non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation, especially in the Western World. Although cirrhosis constitutes the main risk factor for HCC development, in patients with NAFLD, HCC can arise in the absence of cirrhosis, indicating specific carcinogenic molecular pathways. Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population, NAFLD-HCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes. In this current review, we summarize the latest literature on the epidemiology, other than liver cirrhosis-pathogenesis, risk factors and prognosis of NAFLD-HCC patients. Finally, we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.

Keywords: Non-alcoholic fatty liver disease, Hepatocellular carcinoma, Epidemiology, Risk factors, Surveillance, Risk stratification

Core Tip: Non-alcoholic fatty liver disease (NAFLD) is projected to emerge as the leading cause of hepatocellular carcinoma (HCC) worldwide. Demographic factors, genetic predisposition and behavioral parameters have been identified as independent risk factors for NAFLD-related HCC, which can arise even in the absence of cirrhosis. Currently, the most challenging issue for the scientific community worldwide is the identification of the pre-cirrhotic NAFLD patients who have increased risk for HCC. Noteworthy, the central concept for the surveillance policies in the near future should be the identification, via an individual, risk-assessment based precision screening of high-risk NAFLD patients, cirrhotic or not.