Ammonia levels are orchestrated by a series of complex interrelated pathways in which the urea cycle has a central role. Liver dysfunction leads to an accumulation of ammonia, which is toxic and is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, hypoxaemia and dysregulation of neurotransmission. Hyperammonaemia is a hallmark of hepatic encephalopathy and has been strongly associated with liver-related outcomes in patients with cirrhosis and liver failure. In addition to the established role of ammonia as a neurotoxin in the pathogenesis of hepatic encephalopathy, an increasing number of studies suggest that it can lead to hepatic fibrosis progression, sarcopenia, immune dysfunction and cancer. However, elevated systemic ammonia levels are uncommon in patients with metabolic dysfunction-associated steatotic liver disease. A clear causal relationship between ammonia-induced immune dysfunction and risk of infection has not yet been definitively proven. In this Review, we discuss the mechanisms by which ammonia produces its diverse deleterious effects and their clinical relevance in liver diseases, the importance of measuring ammonia levels for the diagnosis of hepatic encephalopathy, the prognosis of patients with cirrhosis and liver failure, and how our knowledge of inter-organ ammonia metabolism is leading to the development of novel therapeutic approaches.

氨水平由一系列复杂的相互关联的途径精心编排，其中尿素循环起着核心作用。肝功能障碍导致氨的积累，氨是有毒的，与钾稳态破坏、线粒体功能障碍、氧化应激、炎症、低氧血症和神经传递失调密切相关。高氨血症是肝性脑病的标志，与肝硬化和肝衰竭患者的肝脏相关结局密切相关。除了氨作为神经毒素在肝性脑病发病机制中的作用外，越来越多的研究表明，它可导致肝纤维化进展、肌肉减少症、免疫功能障碍和癌症。然而，全身氨水平升高在代谢功能障碍相关脂肪性肝病患者中并不常见。氨诱导的免疫功能障碍与感染风险之间的明确因果关系尚未得到明确证实。在本综述中，我们讨论了氨产生各种有害作用的机制及其在肝病中的临床相关性，测量氨水平对诊断肝性脑病的重要性，肝硬化和肝功能衰竭患者的预后，以及我们对器官间氨代谢的了解如何导致新治疗方法的发展。