Influence of sex in the development of liver diseases

The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis and treatment do prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus female patients have 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 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 contributing 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 has long been sex unbalanced, with female subjects underestimated. As such, this review focus on sex disparities of liver diseases and summarizes current understanding of sex specific mechanisms, including sex hormones, sex chromosome, etc. We anticipate that understanding sex-specific pathogenesis will aid in promoting personalized therapies of liver disease among male versus female patients.

Publication History

Received: 18 October 2024

Accepted after revision: 13 January 2025

Accepted Manuscript online:
14 January 2025