Serum Ammonia in Cirrhosis: Clinical Impact of Hyperammonemia, Utility of Testing, and National Testing Trends

Ammonia is central to the pathophysiology of hepatic encephalopathy (HE) in cirrhosis. Serum ammonia levels have prognostic value and have been implicated in sarcopenia, hepatotoxicity, and immune dysfunction. Studies indicate that clinicians frequently order serum ammonia levels in decompensated cirrhosis; however, the clinical utility of serum ammonia levels has been questioned, citing challenges in accurate measurement and interpretation. This article involves a primary review of the literature to evaluate the importance of serum ammonia in cirrhosis and examines the clinical utility of serum ammonia levels in the management of HE. In addition to the review, we conducted primary research using national claims data to investigate national trends in practitioner use of serum ammonia. We identified all hospitalizations in a national commercial claims database with and without ammonia testing among adults with noncirrhotic chronic liver disease and cirrhosis from January 1, 2007, to September 31, 2015. We calculated the proportion of hospitalizations with ammonia testing and the number of ammonia tests per 1000 hospital-days. Proportion of hospitalizations with ammonia testing and ammonia tests per 1000 inpatient-days increased significantly from 2007 to 2015, and particularly in 2014 and 2015, for all groups. A review of the literature indicated that elevated serum ammonia contributes to neurotoxicity, sarcopenia, and immune dysfunction in cirrhosis. However, serum ammonia testing has not had consistent benefit in clinical diagnosis or management of HE in cirrhosis. Claims data indicated that ammonia testing increased substantially during the study period, particularly after the advent of electronic medical record systems. The rapid increase in testing may suggest that electronic health records play a crucial role in test volume by facilitating easy ordering and could be leveraged to improved value-based serum ammonia ordering. Serum ammonia levels may also benefit from standardized guidelines on collection, laboratory analysis, and interpretation.