Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma

Stephanie Talamantes; Michela Lisjak; Eduardo H Gilglioni; Camilo J Llamoza-Torres; Bruno Ramos-Molina; Esteban N Gurzov

doi:10.1016/j.jhepr.2023.100811

Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma

JHEP Rep. 2023 Jun 9;5(9):100811. doi: 10.1016/j.jhepr.2023.100811. eCollection 2023 Sep.

Authors

Stephanie Talamantes¹, Michela Lisjak¹, Eduardo H Gilglioni¹, Camilo J Llamoza-Torres^{2

3}, Bruno Ramos-Molina³, Esteban N Gurzov^{1

3

4}

Affiliations

¹ Signal Transduction and Metabolism Laboratory, Laboratoire de Gastroentérologie Expérimental et Endotools, Université Libre de Bruxelles, Route de Lennik 808, Brussels, 1070, Belgium.
² Department of Hepatology, Virgen de la Arrixaca University Hospital, Murcia, 30120, Spain.
³ Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), Murcia, 30120, Spain.
⁴ WELBIO Department, WEL Research Institute, Avenue Pasteur 6, Wavre, 1300, Belgium.

Abstract

Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.

Keywords: Hepatocellular carcinoma; hepatocyte transformation; non-alcoholic fatty liver disease; obesity; type 2 diabetes.

Publication types

Review