Differentiation of minimal and grade 1 hepatic encephalopathy using neurophysiological, neuropsychological, magnetic resonance spectroscopic, and systemic inflammatory parameters

BACKGROUND Hepatic encephalopathy (HE) is traditionally classified as overt and minimal HE (MHE). The International Society for HE and Nitrogen Metabolism clubbed MHE and grade 1 HE as “covert” HE. However, these appear to be distinct entities. AIM To compare inflammatory markers, magnetic resonance spectroscopy (MRS), Bispectral index (BIS), spectral electroencephalography (EEG), and natural history of MHE and grade 1 HE. METHODS In this prospective study, 150 patients with cirrhosis were categorized into three groups: No HE (n = 50), MHE (n = 50), and grade 1 HE (n = 50). Patients were assessed using the West Haven criteria, the psychometric HE score, critical flicker frequency, MRS, inflammatory markers (cytokines and endotoxins), BIS, and spectral EEG. All patients were followed up for HE progression, complications, hospitalizations, and mortality over 12 months. RESULTS Patients with grade 1 HE showed significantly higher levels of ammonia (164.08 ± 30.12 vs 123.42 ± 19.97, P < 0.001), endotoxins (0.60 ± 0.05 vs 0.47 ± 0.04, P < 0.001), and cytokines than those with MHE. MRS in grade 1 HE revealed reduced myoinositol (-0.2 vs -0.11, P < 0.001) and choline levels (0.38 ± 0.33 vs 0.42 ± 0.18, P < 0.001) and elevated glutamine levels (1.01 ± 0.38 vs 0.73 ± 0.23, P < 0.001) compared to MHE. BIS values were lower in grade 1 HE compared to MHE (72.9 ± 5.49 vs 81.48 ± 3.9, P < 0.001). Spectral EEG metrics effectively distinguished MHE from grade 1 HE with high diagnostic accuracies. Model for end-stage liver disease, interleukin-12, BIS, and spectral EEG changes were independent predictors of survival. CONCLUSION MHE and grade 1 HE exhibit distinct inflammatory, neuropsychological, and neurophysiological profiles, as well as differences in their survival.