The role of ammonia measurement in patients with cirrhosis: an international Delphi consensus on behalf of ISHEN

Background and Aims: Ammonia is a neurotoxin implicated in the pathogenesis ofhepatic encephalopathy (HE). Yet, the clinical utility of blood ammonia measurement inpatients with cirrhosis remains controversial due to methodological variability,inconsistent interpretation, and lack of standardized guidance. The aim of thisconsensus document, developed by the International Society for HepaticEncephalopathy and Nitrogen Metabolism (ISHEN), is to provide evidence-basedrecommendations on the role of ammonia measurement in the diagnosis, monitoring,and treatment of patients with cirrhosis.Methods: A modified Delphi process wasconducted involving a multidisciplinary and international panel of experts in cirrhosisand ammonia metabolism. The writing committee comprised 11-experts and thepanellists 39-members who were chosen by ISHEN, considering their expertise, globalrepresentation and gender balance. 25-PICO questions were generated. Followingliterature review and based on the level of evidence, recommendations and statementswere formulated. The questions, recommendations and statements underwentapproval through 4 Delphi rounds. Results: The panel reached >90% consensus on allthe questions, including the clinical significance of ammonia as a biomarker in bothinpatient and outpatient settings, best practices for sample collection and analysis, andthe role of ammonia in risk-stratification, therapeutic monitoring, and prognostication.Specific research gaps were identified, including the need for point-of-care ammoniatesting, validation of ammonia-based risk models and better characterization of nonhyperammonemicencephalopathy.Conclusions:This ISHEN Consensus is the firststructured international effort to define the role of ammonia measurement in the care ofpatients with cirrhosis. It offers practical recommendations for clinicians, outlinespriorities for future research, and provides a foundation for harmonizing clinical practiceand trial design related to ammonia and HE.