Zhang Jie-Wen, Zhang Nan, Lyu Yi, Zhang Xu-Feng
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Semin Liver Dis. 2025 Mar;45(1):15-32. doi: 10.1055/a-2516-0261. Epub 2025 Jan 14.
The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis, and treatment prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus female patients has not been fully elucidated. Biological sex differences in normal physiology and disease arise principally from sex hormones and/or sex chromosomes. Sex hormones contribute to the development and progression of most liver diseases, with estrogen- and androgen-mediated signaling pathways mechanistically involved. In addition, genetic factors in sex chromosomes have recently been found to contribute to the sex disparity of many liver diseases, which might explain, to some extent, the difference in gene expression pattern, immune response, and xenobiotic metabolism between men and women. Although increasing evidence suggests that sex is one of the most important modulators of disease prevalence and outcomes, at present, basic and clinical studies have long been sex unbalanced, with female subjects underestimated. As such, this review focuses on sex disparities of liver diseases and summarizes the current understanding of sex-specific mechanisms, including sex hormones, sex chromosomes, etc. We anticipate that understanding sex-specific pathogenesis will aid in promoting personalized therapies for liver disease among male versus female patients.
肝脏是一个具有性别二态性的器官。在大多数肝脏疾病中，患病率、进展、预后和治疗方面的性别差异普遍存在，而肝脏疾病在男性和女性患者中表现不同的机制尚未完全阐明。正常生理和疾病中的生物性别差异主要源于性激素和/或性染色体。性激素促成了大多数肝脏疾病的发生和发展，雌激素和雄激素介导的信号通路在其中发挥了机制性作用。此外，最近发现性染色体中的遗传因素也导致了许多肝脏疾病的性别差异，这在一定程度上可能解释了男性和女性在基因表达模式、免疫反应和外源性物质代谢方面的差异。尽管越来越多的证据表明性别是疾病患病率和转归的最重要调节因素之一，但目前基础和临床研究长期存在性别失衡，女性受试者未得到充分重视。因此，本综述聚焦于肝脏疾病的性别差异，并总结了目前对性别特异性机制的认识，包括性激素、性染色体等。我们预计，了解性别特异性发病机制将有助于推动针对男性和女性患者的肝脏疾病个性化治疗。
