Ammonia Measurement in Cirrhosis: Journal of Hepatology| March 2026

Introduction

Ammonia has long been recognized as a central neurotoxin in the pathogenesis of hepatic encephalopathy, but its clinical use in cirrhosis has remained inconsistent because of major variability in sampling, processing, reporting, and interpretation. This international ISHEN Delphi consensus is important because it is the first structured, evidence-based effort to define when ammonia should be measured, how it should be measured, and how clinicians should interpret it in both outpatient and inpatient cirrhosis care. The document moves the field beyond the old debate of whether ammonia is useful at all and instead places ammonia within a practical clinical framework.

Summary

The consensus makes a strong methodological point that ammonia is only clinically useful when measured properly. It recommends a minimum 4-hour fasting period, venous sampling for routine practice, transport on ice, centrifugation within 15 minutes, and measurement within 2 hours. It also advises that ammonia should be reported both as an absolute value and as a multiple of the upper limit of normal to improve comparability across laboratories. In the outpatient setting, ammonia is positioned as a useful biomarker for risk stratification, especially for predicting overt hepatic encephalopathy, liver-related decompensation, and death, with a level greater than 1.4 times the upper limit of normal emerging as an important prognostic threshold. In patients undergoing elective TIPS, pre-procedure ammonia may help predict post-TIPS encephalopathy. In the inpatient setting, ammonia is not considered a standalone diagnostic test for overt hepatic encephalopathy, but a normal value should prompt clinicians to question the diagnosis and search for alternative causes of altered mental status. The consensus also emphasizes that serial ammonia measurement has value during treatment, because falling ammonia levels are associated with better neurological recovery and improved survival, whereas persistent or rising ammonia suggests poor response and worse prognosis.

Conclusion

The major clinical message of this ISHEN consensus is that ammonia should no longer be dismissed as an unreliable biomarker, but neither should it be used in isolation. When measured under standardized conditions and interpreted within the full clinical context, ammonia provides meaningful diagnostic, prognostic, and therapeutic information in cirrhosis. This document is likely to influence day-to-day hepatology practice, future trial design, and global harmonization of care in hepatic encephalopathy.