Nitric oxide, ammonia, and CRP levels in cirrhotic patients with hepatic encephalopathy: is there a connection?

Goals: Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice.

Background: HE is a neuropsychiatric complication of cirrhosis. The exact pathogenetic mechanisms underlying the presence of HE are not known. However, dysfunction of the NO pathway and ammonia detoxification are thought to play a major role.

Study: Sixty-seven cirrhotic patients, 36 (53.7%) without HE, and 31 (46.3%) with HE were included in the study. Eighteen healthy individuals were used as control group. Clinical and laboratory data, including ammonia and stable end products of NO using Griess reaction, were collected.

Results: NOx levels were statistically significantly higher in cirrhotic patients (225.5 μmol/L) than in control group [(67.94 μmol/L) (P=0.000)]. NOx levels were, also, statistically significantly higher in patients with HE compared with patients without HE (324.67 μmol/L vs. 141.96 μmol/L, P=0.000). Significant correlation between the presence of HE and NOx, ammonia, C-reactive protein, albumin, Model for End-Stage Liver Disease score, and Child-Pugh classification revealed. NOx levels also correlated with severity of HE. NOx and ammonia are independent factors predicting HE according to regression analysis. Diagnostic accuracy for the diagnosis of HE using a combination of NOx and ammonia was superior compared with standalone NOx or ammonia utilization.

Conclusions: NOx levels are correlated with the presence and severity of HE. NOx levels determination, in addition to ammonia levels, could contribute in diagnosis of HE.