The Value of Ammonia as a Biomarker in Patients with Cirrhosis

Abstract

Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with cirrhosis and plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). Despite being one of the main drivers of brain dysfunction, for many years international societies stated that increased blood ammonia does not add any diagnostic, staging, or prognostic value for HE in patients with cirrhosis. Nonetheless, in the last decades, evidence is emerging that supports the utility of ammonia for risk stratification, but its role in guiding HE diagnosis, staging, and treatment is unclear and there is equipoise in its use in clinical practice. This review provides the latest evidence on the value of ammonia as a biomarker in patients with cirrhosis. Although correct measurement of ammonia requires disciplined sample collection, it provides extremely useful clinical guidance for the diagnosis of HE, offers prognostic information, and it defines a therapeutic target.

Fig. 1

Proposed algorithm for assessment of overt hepatic encephalopathy in hospitalized patients with cirrhosis (adapted from Häussinger et al 9 ). Measurement of ammonia levels in patients with neurological symptoms and normal CT scan is based on the latest EASL guideline. Measurement of ammonia levels in patients hospitalized without neurological symptoms is based on the current evidence for the importance of ammonia as a prognostic biomarker ( Table 2 ). CT, computed tomography; EASL, European Association for the Study of the Liver.

Fig. 2

Summary of the pathophysiological pathways that each therapy targets for the treatment of hepatic encephalopathy.

Fig. 3

Proposed algorithm based on the AMMON-OHE model to stratify the risk of overt hepatic encephalopathy in clinically stable outpatients with cirrhosis and optimize their management.