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CC BY-NC-ND 4.0 · Semin Liver Dis 2024; 44(02): 147-158
DOI: 10.1055/a-2289-2298
Review Article

Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma

Takahiro Kodama
1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
,
Tetsuo Takehara
1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
› Author Affiliations Funding This work was supported by the Japan Agency for Medical Research and Development under grant numbers JP23fk0210131 (T.K.), JP 23ama221410 (T.K.), and JP23ck0106793 (T.K.), and by a Grant-in-Aid for Scientific Research (T.K.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, under grant number 23H02893.
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Abstract

This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways. Furthermore, a notable frequency of single nucleotide polymorphisms in genes such as patatin-like phospholipase domain-containing 3, transmembrane 6 superfamily member 2, glucokinase regulator, and membrane-bound O-acyltransferase domain-containing 7 has been observed. The tumor immune microenvironment of metabolic-associated HCC is characterized by unique phenotypes of macrophages, neutrophils, and T lymphocytes. Additionally, the pathogenesis of metabolic-associated HCC is influenced by abnormal lipid metabolism, insulin resistance, and dysbiosis. In conclusion, deciphering the intricate interactions among metabolic processes, genetic predispositions, inflammatory responses, immune regulation, and microbial ecology is imperative for the development of novel therapeutic and preventative measures against metabolic-associated HCC.

Keywords

MASLD - NAFLD - dysbiosis - lipid metabolism - insulin signaling


Publication History

Accepted Manuscript online:
18 March 2024

Article published online:
18 April 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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