Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study

Purpose: We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction.Methods: In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. H-1-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann-Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses.Results: Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 +/- 0.07 vs. 0.74 +/- 0.19, P = 0.025) and increased Glx/tCr (1.79 +/- 0.17 vs. 2.07 +/- 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = -0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = -0.379, P = 0.033).Conclusion: Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.