Chronic liver disease is a major cause of morbidity and mortality worldwide. Epidemiology, clinical phenotype and response to therapies for gastrointestinal and liver diseases are commonly different between women and men due to sex-specific hormonal, genetic and immune-related factors. The hepatic immune system has unique regulatory functions that promote the induction of intrahepatic tolerance, which is key for maintaining liver health and homeostasis. In liver diseases, hepatic immune alterations are increasingly recognized as a main cofactor responsible for the development and progression of chronic liver injury and fibrosis. In this Review, we discuss the basic mechanisms of sex disparity in hepatic immune regulation and how these mechanisms influence and modify the development of autoimmune liver diseases, genetic liver diseases, portal hypertension and inflammation in chronic liver disease. Alterations in gut microbiota and their crosstalk with the hepatic immune system might affect the progression of liver disease in a sex-specific manner, creating potential opportunities for novel diagnostic and therapeutic approaches to be evaluated in clinical trials. Finally, we identify and propose areas for future basic, translational and clinical research that will advance our understanding of sex disparities in hepatic immunity and liver disease.

慢性肝病是全世界发病率和死亡率的主要原因。由于性别特异性的激素、遗传和免疫相关因素，女性和男性的流行病学、临床表型和对治疗的反应通常不同。肝脏免疫系统具有独特的调节功能，可促进肝内耐受的诱导，这是维持肝脏健康和体内平衡的关键。在肝脏疾病中，肝脏免疫改变越来越被认为是导致慢性肝损伤和纤维化发展和进展的主要辅助因子。在本综述中，我们讨论了肝脏免疫调节中性别差异的基本机制，以及这些机制如何影响和改变自身免疫性肝病、遗传性肝病、门静脉高压症和慢性肝病炎症的发展。肠道微生物群的改变及其与肝脏免疫系统的串扰可能会以性别特异性的方式影响肝病的进展，从而为在临床试验中评估新的诊断和治疗方法创造潜在机会。最后，我们确定并提出了未来基础、转化和临床研究的领域，这将促进我们对肝脏免疫和肝病性别差异的理解。