Despite tremendous research advancements in nonalcoholic fatty liver disease (NAFLD), our understanding of sex differences in NAFLD remains insufficient. This review summarizes the current knowledge on sex differences in NAFLD, identifies gaps, and discusses important considerations for future research. The prevalence and severity of NAFLD are higher in men than in women during the reproductive age. However, after menopause, NAFLD occurs at a higher rate in women, suggesting that estrogen is protective. Sex differences also exist for the major risk factors of NAFLD. In general, animal models of NAFLD recapitulate the sex differences observed in patients, with more severe steatosis and steatohepatitis, more proinflammatory/profibrotic cytokines, and a higher incidence of hepatic tumors in male than female subjects. Based on computer modeling, female and male livers are metabolically distinct with unique regulators modulating sex‐specific metabolic outcomes. Analysis of the literature reveals that most published clinical and epidemiological studies fail to examine sex differences appropriately. Considering the paucity of data on sex differences and the knowledge that regulators of pathways relevant to current therapeutic targets for NAFLD differ by sex, clinical trials should be designed to test drug efficacy and safety according to sex, age, reproductive stage (i.e., menopause), and synthetic hormone use. Conclusion: Sex differences do exist in the prevalence, risk factors, fibrosis, and clinical outcomes of NAFLD, suggesting that, while not yet incorporated, sex will probably be considered in future practice guidelines; adequate consideration of sex differences, sex hormones/menopausal status, age, and other reproductive information in clinical investigation and gene association studies of NAFLD are needed to fill current gaps and implement precision medicine for patients with NAFLD.

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NAFLD 的性别差异：最新技术和研究差距的识别

尽管非酒精性脂肪性肝病 (NAFLD) 的研究取得了巨大进展，但我们对 NAFLD 性别差异的理解仍然不足。本综述总结了当前关于 NAFLD 性别差异的知识，确定了差距，并讨论了未来研究的重要考虑因素。在育龄期间，男性 NAFLD 的患病率和严重程度高于女性。然而，绝经后，女性 NAFLD 的发生率更高，这表明雌激素具有保护作用。NAFLD 的主要危险因素也存在性别差异。一般来说，NAFLD 的动物模型概括了在患者中观察到的性别差异，男性比女性受试者具有更严重的脂肪变性和脂肪性肝炎、更多的促炎/促纤维化细胞因子以及更高的肝脏肿瘤发生率。基于计算机建模，雌性和雄性肝脏在代谢上是不同的，具有独特的调节器调节性别特异性代谢结果。文献分析表明，大多数已发表的临床和流行病学研究未能适当地检查性别差异。考虑到性别差异数据的缺乏以及与当前 NAFLD 治疗靶点相关的通路调节剂因性别而异的知识，临床试验应设计为根据性别、年龄、生殖阶段（即更年期）测试药物疗效和安全性和合成激素的使用。结论：NAFLD 的患病率、危险因素、纤维化和临床结果确实存在性别差异，这表明虽然尚未纳入，但在未来的实践指南中可能会考虑性别；充分考虑性别差异，