Ammonia measurement in cirrhosis: International Delphi consensus recommendations from ISHEN

Autores de IIS La Fe

• 

  Marina Berenguer Haym

  Autor

Participantes ajenos a IIS La Fe

• Ballester M.P.
• Gallego-Durán R.
• Shalimar
• Thomsen K.L.
• Karvellas C.J.
• Dasarathy S.
• Shawcross D.L.
• Thabut D.
• Chen J.
• Rose C.F.
• Jalan R.
• Montano-Loza A.J.
• Torre A.
• Berzigotti A.
• Kerbert A.
• Rabiee A.
• Agarwal B.
• Minguez B.
• Labenz C.
• Bureau C.
• Engelmann C.
• Ripoll C.
• Lee E.
• Williams F.
• Vilstrup H.
• Towey J.
• Carbonell-Asins J.A.
• Gananandan K.
• Weissenborn K.
• Kjaergaard K.
• Ridola L.
• Romero M.
• Merli M.
• Rudler M.
• Swain M.
• Mandorfer M.
• Lauridsen M.
• Coenraad M.
• Weiss N.
• Andrenacci P.
• Bloom P.
• Ott P.
• Maiwall R.
• Hernaez R.
• Montagnese S.
• Asrani S.
• Reiberger T.
• Frederick R.T.
• Bernal W.

Grupos

• Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

Abstract

Background & Aims Ammonia is a neurotoxin implicated in the pathogenesis of hepatic encephalopathy (HE). Yet, the clinical utility of blood ammonia measurement in patients with cirrhosis remains controversial due to methodological variability, inconsistent interpretation, and lack of standardised guidance. The aim of this consensus document, developed by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), is to provide evidence-based recommendations on the role of ammonia measurement in the diagnosis, monitoring, and treatment of patients with cirrhosis. Methods A modified Delphi process was conducted involving a multidisciplinary and international panel of experts in cirrhosis and ammonia metabolism. The writing committee comprised 11 experts, and the panel included 39 members selected by ISHEN based on expertise, global representation, and gender balance. Twenty-five PICO questions were generated. Following literature review and based on the level of evidence, recommendations and statements were formulated. The questions, recommendations, and statements underwent approval across four Delphi rounds. Results The panel reached =90% consensus on all the questions, including the clinical significance of ammonia as a biomarker in both inpatient and outpatient settings, best practices for sample collection and analysis, and the role of ammonia in risk stratification, therapeutic monitoring, and prognostication. Specific research gaps were identified, including the need for point-of-care ammonia testing, validation of ammonia-based risk models and better characterisation of non-hyperammonemic encephalopathy. Conclusions This ISHEN consensus is the first structured international effort to define the role of ammonia measurement in the care of patients with cirrhosis. It offers practical recommendations for clinicians, outlines priorities for future research, and provides a foundation for harmonizing clinical practice and trial design related to ammonia and HE. Impact and implications This is the first international, evidence-based consensus describing the role of ammonia measurement in patients with cirrhosis. The consensus details guidance on how to measure ammonia, the role of ammonia measurement in predicting development of overt hepatic encephalopathy and other liver-related complications, and its role in the diagnosis and prognosis of patients with overt hepatic encephalopathy. This document will help harmonise practices across the world in the way ammonia should be measured and reported, impacting significantly on patient outcomes, research and drug development efforts. © 2026 The Author(s).

Keywords

• Ammonia; Biomarkers; Delphi Technique; Hepatic Encephalopathy; Humans; Liver Cirrhosis; ammonia; biological marker; ammonia; biological marker; acute on chronic liver failure; ammonia blood level; arterial blood; Article; brain disease; Child Pugh score; decompensated liver cirrhosis; Delphi study; disease severity; elective surgery; end stage liver disease; environmental temperature; fasting; gender; hospital patient; human; hyperammonemia; laboratory test; liver cell carcinoma; liver cirrhosis; measurement accuracy; mortality risk; nonhyperammonemic encephalopathy; outpatient; point of care testing; prophylaxis; psychometry; recurrent disease; reproducibility; risk model; spontaneous portosystemic shunt; transjugular intrahepatic portosystemic shunt; treatment outcome; validation study; venous blood; blood; complication; diagnosis; etiology; hepatic encephalopathy; liver cirrhosis