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Benhammou et al. Hepatoma Res 2020;6:35 Hepatoma Research
DOI: 10.20517/2394-5079.2020.16

Review Open Access

Emerging risk factors for nonalcoholic fatty liver
disease associated hepatocellular carcinoma

Jihane N. Benhammou , Jonathan Lin , Shehnaz K. Hussain , Mohamed El-Kabany
3,4
2
1
1
1 Pfleger Liver Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
2 Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA
90095, USA.
3 Department of Epidemiology, Fielding School of Public Health, University of California, CA 90095, USA.
4 Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
90048, USA.
Correspondence to: Dr. Mohamed El-Kabany, Pfleger Liver Institute, 200 Medical Plaza, Los Angeles, CA 90095, USA.
E-mail: melkabany@mednet.ucla.edu

How to cite this article: Benhammou JN, Lin J, Hussain SK, El-Kabany M. Emerging risk factors for nonalcoholic fatty liver
disease associated hepatocellular carcinoma. Hepatoma Res 2020;6:35. http://dx.doi.org/10.20517/2394-5079.2020.16
Received: 24 Feb 2020 First Decision: 24 Apr 2020 Revised: 6 May 2020 Accepted: 13 May 2020 Published: 18 Jun 2020

Science Editor: Guido Guenther Gerken Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel,
hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Epidemiological studies have not
only shed light on the prevalence and incidence of the disease but have also unmasked important environmental
risk factors, including the role of diabetes and dyslipidemia in disease pathogenesis. Genetic association studies
have identified single nucleotide polymorphisms implicated in NAFLD-HCC, many of which are part of lipid
metabolism pathways. Through these clinical studies and subsequently, translational and basic research, the
role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in
HCC prevention and treatment. In this review, we summarize the recent epidemiological studies describing the
burden of NAFLD-HCC in different patient populations and countries. We discuss the genetic and environmental
risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin. We also summarize
what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of
surveillance in NAFLD-HCC patients.

Keywords: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatocellular carcinoma, statins,
metabolic syndrome

INTRODUCTION
The metabolic syndrome (MetS), defined by the clustering of biochemical and clinical features, which
[1]
includes type 2 diabetes (T2D), hypertension, dyslipidemia and obesity, has reached epidemic proportions .
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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