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Li et al. Metab Target Organ Damage. 2025;5:19 Metabolism and
DOI: 10.20517/mtod.2025.05
Target Organ Damage

Commentary Open Access

Metabolism, sex, and what lies beyond the scalpel in
MASLD

Zong-Long Li 1,2,3 , Yue Tang 1,2,3 , De-Long Qin 1,2,3 , Jia-Lu Chen 1,2,3 , Zhao-Hui Tang 1,2,3
1
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
2
Department of Blood Transfusion, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092,
China.
3
Department of Blood Transfusion, The Chongming Branch of Xinhua Hospital, School of Medicine, Shanghai Jiao Tong
University, Shanghai 202150, China.
Correspondence to: Prof. Zhao-Hui Tang, Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao
Tong University, Kongjiang Road NO.1665, Yangpu Distinct, Shanghai 200092, China. E-mail: tzh1236@163.com

How to cite this article: Li ZL, Tang Y, Qin DL, Chen JL, Tang ZH. Metabolism, sex, and what lies beyond the scalpel in MASLD.
Metab Target Organ Damage. 2025;5:19. https://dx.doi.org/10.20517/mtod.2025.05
Received: 14 Jan 2025 First Decision: 10 Feb 2025 Revised: 24 Feb 2025 Accepted: 28 Feb 2025 Published: 2 Apr 2025

Academic Editor: Ralf Weiskirchen Copy Editor: Ting-Ting Hu Production Editor: Ting-Ting Hu

Abstract
The discovery of the one-carbon metabolism-homocysteine-metabolic dysfunction-associated steatotic liver
disease (OCM-Hcy-MASLD) axis has renewed our understanding of MASLD-related primary liver cancer (PLC).
Based on Suzuki et al.’s mathematical modeling findings of diminished cystathionine β-synthase (CBS) and
phosphatidylethanolamine N-methyltransferase (PEMT) expression in MASLD, this commentary analyzes recent
findings regarding sex-specific variations in this axis and their implications for surgical management. We highlight
how the integration of OCM-Hcy pathway modulation with precise surgical interventions could enhance
perioperative outcomes and long-term prognosis. The emerging evidence suggests that targeted metabolic
interventions, particularly those accounting for sex differences, may complement traditional surgical approaches by
addressing the systemic nature of MASLD-related PLC. This paradigm shift from purely surgical resection toward
comprehensive metabolic regulation marks a significant advance in precision medicine for hepatobiliary surgery,
potentially improving both perioperative safety and oncological outcomes.

Keywords: MASLD, OCM, primary liver cancer, sex differences, precision medicine

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0
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