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World J Hepatol. Feb 27, 2022; 14(2): 354-371
Published online Feb 27, 2022. doi: 10.4254/wjh.v14.i2.354
Hepatocellular carcinoma in patients with metabolic dysfunction-associated fatty liver disease: Can we stratify at-risk populations?
Eduardo Fassio, Fernando J Barreyro, M Soledad Pérez, Diana Dávila, Graciela Landeira, Gisela Gualano, Gabriela Ruffillo
Eduardo Fassio, M Soledad Pérez, Diana Dávila, Graciela Landeira, Gisela Gualano, Gabriela Ruffillo, Hepatology Section, Gastroenterology Service, Hospital Nacional Prof. Alejandro Posadas, El Palomar 1684, Buenos Aires, Argentina
Fernando J Barreyro, Biotechnology Institute of Misiones, Faculty of Chemical and Natural Sciences, National University of Misiones, Posadas N3300, Misiones, Argentina
Author contributions: This is not a research article but a review work; all authors contributed equally to the bibliographic search, to the reading and interpretation of the selected articles; Fassio E and Barreyro FJ wrote most of the text; all authors have read and approved the final manuscript.
Conflict-of-interest statement: Authors have nothing to declare with respect to this work.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Eduardo Fassio, MD, Chief of Gastroenterology Service, Hepatology Section, Gastroenterology Service, Hospital Nacional Prof. Alejandro Posadas, Av. Presidente Illia y Marconi, s/n, El Palomar 1684, Buenos Aires, Argentina. efassio@intramed.net
Received: March 18, 2021
Peer-review started: March 18, 2021
First decision: July 18, 2021
Revised: August 22, 2021
Accepted: January 25, 2022
Article in press: January 25, 2022
Published online: February 27, 2022
Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new nomenclature recently proposed by a panel of international experts so that the entity is defined based on positive criteria and linked to pathogenesis, replacing the traditional non-alcoholic fatty liver disease (NAFLD), a definition based on exclusion criteria. NAFLD/MAFLD is currently the most common form of chronic liver disease worldwide and is a growing risk factor for development of hepatocellular carcinoma (HCC). It is estimated than 25% of the global population have NAFLD and is projected to increase in the next years. Major Scientific Societies agree that surveillance for HCC should be indicated in patients with NAFLD/ MAFLD and cirrhosis but differ in non-cirrhotic patients (including those with advanced fibrosis). Several studies have shown that the annual incidence rate of HCC in NAFLD-cirrhosis is greater than 1%, thus surveillance for HCC is cost-effective. Risk factors that increase HCC incidence in these patients are male gender, older age, presence of diabetes and any degree of alcohol consumption. In non-cirrhotic patients, the incidence of HCC is much lower and variable, being a great challenge to stratify the risk of HCC in this group. Furthermore, large epidemiological studies based on the general population have shown that diabetes and obesity significantly increase risk of HCC. Some genetic variants may also play a role modifying the HCC occurrence among patients with NAFLD. The purpose of this review is to discuss the epidemiology, clinical and genetic risk factors that may influence the risk of HCC in NAFLD/MAFLD patients and propose screening strategy to translate into better patient care.

Keywords: Hepatocellular carcinoma, Metabolic dysfunction-associated fatty liver disease, Nonalcoholic fatty liver disease, Surveillance for hepatocellular carcinoma, Incidence of hepatocellular carcinoma, Nonalcoholic steatohepatitis

Core Tip: Metabolic dysfunction-associated fatty liver disease (MAFLD) affects 25% of general population worldwide. Within that huge number of patients, a minority will progress to cirrhosis, with an annual incidence rate of hepatocellular carcinoma (HCC) > 1%. In them, surveillance for HCC by means of ultrasound with or without alpha-fetoprotein measurement is cost-effective. In patients with MAFLD cirrhosis who are men, older and diabetic, risk is even higher and magnetic resonance imaging might be a better screening test. However, the great challenge is stratifying the HCC risk in patients with MAFLD without cirrhosis. Factors that can help to stratify their risk (genetic, demographic, metabolic, non-invasive fibrosis tests) will be reviewed.