The liver is often thought of as a single functional unit, but both its structural and functional architecture make it highly multivalent and adaptable. In any given physiological situation, the liver can maintain metabolic homeostasis, conduct appropriate inflammatory responses, carry out endobiotic and xenobiotic transformation and synthesis reactions, as well as store and release multiple bioactive molecules. Moreover, the liver is a very resilient organ. This resilience means that chronic liver diseases can go unnoticed for decades, yet culminate in life-threatening clinical complications once the adaptive capacity of the liver is overwhelmed. Non-alcoholic fatty liver disease (NAFLD) predisposes individuals to cirrhosis and increases liver-related and cardiovascular disease-related mortality. This Review discusses the accumulating evidence of sexual dimorphism in NAFLD, which is currently rarely considered in preclinical and clinical studies. Increased awareness of the mechanistic causes of hepatic sexual dimorphism could lead to improved understanding of the biological processes that are dysregulated in NAFLD, to the identification of relevant therapeutic targets and to improved risk stratification of patients with NAFLD undergoing therapeutic intervention.

肝脏通常被认为是一个单一的功能单元，但其结构和功能结构都使其具有高度的多价性和适应性。在任何给定的生理情况下，肝脏都可以维持代谢稳态，进行适当的炎症反应，进行内生和外生转化和合成反应，以及储存和释放多种生物活性分子。此外，肝脏是一个非常有弹性的器官。这种复原力意味着慢性肝病可能会被忽视数十年，但一旦肝脏的适应能力不堪重负，就会导致危及生命的临床并发症。非酒精性脂肪性肝病 (NAFLD) 使个体易患肝硬化并增加肝脏相关和心血管疾病相关的死亡率。本综述讨论了 NAFLD 中性二态性的累积证据，目前在临床前和临床研究中很少考虑这一点。提高对肝脏两性异形性机制原因的认识可能会提高对 NAFLD 中失调的生物学过程的理解，确定相关的治疗靶点，并改善接受治疗干预的 NAFLD 患者的风险分层。