Ammonia in Liver Disease: Diagnostic Utility, Preanalytical Challenges, Clinical Interpretation, and Therapeutic Implications: A Critical Narrative Review

Ammonia is central to the pathogenesis of hepatic encephalopathy (HE), but blood ammonia is neither a stand-alone diagnostic test nor a reliable measure of HE grade. Its clinical value depends on the population, the question being asked, and strict control of preanalytical and analytical conditions. This critical narrative review evaluates ammonia as a diagnostic and prognostic biomarker in liver disease, with emphasis on standardised measurement, interpretation in altered mental status, selective monitoring, and the distinction between biochemical response and patient-important outcomes. Evidence was updated through 9 October 2026 and prioritised international guidelines, the 2026 International Society for Hepatic Encephalopathy and Nitrogen Metabolism consensus, randomised trials, prospective cohorts, systematic reviews, and verified trial registries. In cirrhosis, an elevated value is nonspecific and does not confirm HE, whereas a methodologically reliable normal value should prompt diagnostic reassessment. Ammonia may add prognostic information in stable and decompensated cirrhosis, but thresholds and risk models require population-specific validation and do not independently mandate treatment. In acute liver failure, arterial ammonia has a distinct role in assessing the risk of cerebral oedema. Fasting before planned testing, avoidance of fist clenching and prolonged tourniquet use, rapid chilled transport, prompt plasma separation, and timely analysis are essential for an interpretable result. Treatment should be guided primarily by clinical course, correction of precipitants, and prevention of recurrence rather than serial ammonia concentrations. Standardisation and clinically anchored diagnostic algorithms are necessary before ammonia-guided management can be adopted broadly.