Growing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) is significantly higher in men versus women. Increased prevalence is observed in postmenopausal women, suggesting that age and sex (hormones) influence MASLD development and progression. Molecular data further reveal that sex regulates the innate immune responses with an essential role in MASLD progression. To date, there has been limited focus on the role of innate immune sexual dimorphism in MASLD, and differences between men and women are not considered in the current drug discovery landscape. In this review, we summarize the sex disparities and innate immune sexual dimorphism in MASLD pathogenesis. We further highlight the importance of harnessing sexual dimorphism in identifying therapeutic targets, developing pharmacological therapies, and designing (pre-) clinical studies for the personalized treatment for MASLD.

越来越多的证据表明，男性与女性相比，代谢功能障碍相关的脂肪肝病 (MASLD) 发病率明显更高。在绝经后女性中观察到患病率增加，表明年龄和性别（激素）影响 MASLD 的发生和进展。分子数据进一步表明，性别调节先天免疫反应，在 MASLD 进展中发挥重要作用。迄今为止，人们对先天免疫性二态性在 MASLD 中的作用的关注有限，并且在当前的药物发现领域没有考虑男性和女性之间的差异。在这篇综述中，我们总结了 MASLD 发病机制中的性别差异和先天免疫性别二态性。我们进一步强调了利用性别二态性在确定治疗靶点、开发药物疗法和设计 MASLD 个性化治疗的（预）临床研究方面的重要性。