Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

Alfredo Smiriglia; Nicla Lorito; Marina Serra; Andrea Perra; Andrea Morandi; Marta Anna Kowalik

doi:10.1016/j.isci.2023.108363

Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

iScience. 2023 Oct 30;26(12):108363. doi: 10.1016/j.isci.2023.108363. eCollection 2023 Dec 15.

Authors

Alfredo Smiriglia¹, Nicla Lorito¹, Marina Serra², Andrea Perra², Andrea Morandi¹, Marta Anna Kowalik²

Affiliations

¹ Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
² Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.

Abstract

Only a few preclinical findings are confirmed in the clinic, posing a critical issue for clinical development. Therefore, identifying the best preclinical models can help to dissect molecular and mechanistic insights into liver disease pathogenesis while being clinically relevant. In this context, the sex relevance of most preclinical models has been only partially considered. This is particularly significant in NAFLD and HCC, which have a higher prevalence in men when compared to pre-menopause women but not to those in post-menopausal status, suggesting a role for sex hormones in the pathogenesis of the diseases. This review gathers the sex-relevant findings and the available preclinical models focusing on both in vitro and in vivo studies and discusses the potential implications and perspectives of introducing the sex effect in the selection of the best preclinical model. This is a critical aspect that would help to tailor personalized therapies based on sex.

Keywords: Biological sciences; Cancer; Natural sciences.

Publication types

Review