Clinical question: Do serum ammonia levels correlate with the severity of overt hepatic encephalopathy (OHE) in hospitalized patients with cirrhosis?
Background: Guidelines recommend diagnosing OHE clinically rather than relying on ammonia levels. Nonetheless, clinicians frequently use serum ammonia levels as a marker of OHE severity in hospitalized patients with cirrhosis to guide treatment decisions. This practice leads to an estimated annual expenditure of more than $1 million in the U.S. Thus, there remains significant opportunity to integrate evidence-based medicine and high-value care into clinical practice.
Study design: Secondary review of randomized, double-blinded, placebo-controlled trial
Setting: Multiple hospitals in the U.S. between September 2018 and March 2020
Synopsis: The study investigates the relationship between serum ammonia levels and the severity of OHE in 44 hospitalized patients with cirrhosis who were receiving lactulose therapy. The study found no significant correlation between serum ammonia levels and the severity of OHE. Of note, only 60% of patients clinically diagnosed with OHE had elevated ammonia levels (>72 μmol/L), while patients with elevated ammonia levels did not have correspondingly more severe OHE. There was also no correlation between ammonia level and time to resolution of OHE. Further reducing the utility of serum ammonia levels to guide clinical decision-making, the study also noted substantial interlaboratory variability in ammonia measurements. This study ultimately puts any debate to rest regarding reliance on ammonia levels for guiding diagnosis and treatment decisions in patients with cirrhosis regarding OHE.
Bottom line: While ammonia plays a role in the pathophysiology of hepatic encephalopathy, it lacks clinical utility as a severity marker due to the absence of correlation with OHE in cirrhosis.
Citation: Bajaj JS, et al. Serum ammonia levels do not correlate with overt hepatic encephalopathy severity in hospitalized patients with cirrhosis. Clin Gastroenterol Hepatol. 2024;22(9):1950-1952.e1. doi:10.1016/j.cgh.2024.02.015.

Dr. Signoff
Dr. Signoff is an academic hospitalist in the department of internal medicine and an associate professor at the University of California Davis Medical School in Sacramento, Calif.