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Lonardo et al. Hepatoma Res 2020;6:83 Hepatoma Research
DOI: 10.20517/2394-5079.2020.89

Review Open Access

Sex disparity in hepatocellular carcinoma owing to
NAFLD and non-NAFLD etiology: epidemiological

findings and pathobiological mechanisms

Amedeo Lonardo , Stefano Ballestri , Pierce K. H. Chow , Ayako Suzuki 5,6,7
1
3,4
2
1 Operating Unit of Metabolic Syndrome, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena
41126, Italy.
2 Operating Unit Internal Medicine, Ospedale di Pavullo, Azienda Unità Sanitaria Locale, Modena 41126, Italy.
3 Division of Surgery and Surgical Oncology, National Cancer Center Singapore and Singapore General Hospital, Council 169610,
Singapore.
4 Surgery Academic Clinical Program and Office of Education, Duke-NUS Medical School, Singapore 169857, Singapore.
5 Division of Gastroenterology, Duke University Health System, Durham, NC 27710, USA.
6 Division of Gastroenterology, Durham VA Medical Center, Durham, NC 27705, USA
7 Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.

Correspondence to: Prof. Amedeo Lonardo, Department of Internal Medicine, Ospedale Civile di Baggiovara, 1135 Via Giardini,
Modena 41126, Italy. E-mail: a.lonardo@libero.it
How to cite this article: Lonardo A, Ballestri S, Chow PKH, Suzuki A. Sex disparity in hepatocellular carcinoma owing to NAFLD
and non-NAFLD etiology: epidemiological findings and pathological mechanisms. Hepatoma Res 2020;6:83.
Received: First Decision: Revised: Accepted: Published: http://dx.doi.org/10.20517/2394-5079.2020.89

Science Editor: Copy Editor: Production Editor: Jing Yu Received: 25 Aug 2020 First Decision: 30 Sep 2020 Revised: 1 Nov 2020 Accepted: 11 Nov 2020 Published: 5 Dec 2020
Academic Editor: Stefano Bellentani Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Nonalcoholic fatty liver disease (NAFLD) exhibits sexual dimorphism, with men being more exposed than women
to the risk of simple steatosis, nonalcoholic steatohepatitis fibrosis, and hepatocellular carcinoma (HCC), while the
protection conferred to women seemingly disappears with aging and reproductive senescence (i.e., menopause).
HCC, the most common primary liver cancer, which carries an ominous prognosis, may result from various genetic
and non-genetic risk factors. NAFLD is now projected to become the most common cause of HCC. HCC also
exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio. In this review
article, we focus on sex differences in the epidemiological features of HCC. Moreover, we discuss sex differences
in the clinical outcome and molecular pathobiology of NAFLD-HCC. By highlighting the research gaps to be filled,
the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized
cancer prevention strategies, detection, and treatments to achieve better patient outcomes in NAFLD-HCC,
considering sex differences in HCC pathobiology.

© 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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