Rocío Gallego-Durán, Anna Hadjihambi, Javier Ampuero, Christopher F. Rose, Rajiv Jalan, Manuel Romero-Gómez
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引用次数: 0
Abstract
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. This Review describes inter-organ ammonia metabolism in liver disease and mechanisms underlying the pathogenic effect of hyperammonaemia in hepatic encephalopathy, liver disease progression in metabolic dysfunction-associated steatotic liver disease, immune dysfunction and hepatocellular carcinoma. It also addresses the principles of treating hyperammonaemia.
期刊介绍:
Nature Reviews Gastroenterology & Hepatology aims to serve as the leading resource for Reviews and commentaries within the scientific and medical communities it caters to. The journal strives to maintain authority, accessibility, and clarity in its published articles, which are complemented by easily understandable figures, tables, and other display items. Dedicated to providing exceptional service to authors, referees, and readers, the editorial team works diligently to maximize the usefulness and impact of each publication.
The journal encompasses a wide range of content types, including Research Highlights, News & Views, Comments, Reviews, Perspectives, and Consensus Statements, all pertinent to gastroenterologists and hepatologists. With its broad scope, Nature Reviews Gastroenterology & Hepatology ensures that its articles reach a diverse audience, aiming for the widest possible dissemination of valuable information.
Nature Reviews Gastroenterology & Hepatology is part of the Nature Reviews portfolio of journals.