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

Figure 1 Study flowchart. MRI: Magnetic resonance imaging; HE: Hepatic encephalopathy; GI: Gastrointestinal; SBP: Subacute bacterial peritonitis; HRS: Hepatorenal syndrome; HCC: Hepatocellular carcinoma; ACLF: Acute-on-chronic liver failure; LOLA: L-ornithine L-aspartate; NSAIDs: Non-steroidal anti-inflammatory drugs; TIPSS: Transjugular intrahepatic portosystemic shunt; PHES: Psychometric hepatic encephalopathy score; MHE: Minimal hepatic encephalopathy; CFF: Critical flicker frequency; MRS: Magnetic resonance spectroscopy; EEG: Electroencephalogram.

Figure 2 Receiver operating characteristic curves of inflammatory markers for predicting minimal hepatic encephalopathy. A: Tumor necrosis factor-alpha [area under the receiver operating characteristic (AUROC): 0.934], interleukin-6 (IL-6) (AUROC: 0.864), IL-18 (AUROC: 0.962), endotoxin (AUROC: 0.976), IL-10 (AUROC: 0.976), IL-12 (AUROC: 0.984), IL-1β (AUROC: 0.993); B: Grade 1 hepatic encephalopathy [tumor necrosis factor-alpha (AUROC: 0.729)], IL-6 (AUROC: 0.751), IL-18 (AUROC: 0.812), endotoxin (AUROC: 0.989), IL-10 (AUROC: 0.833), IL-12 (AUROC: 0.921), IL-1β (AUROC: 0.938). TNF-α: Tumor necrosis factor-alpha; IL: Interleukin.

Figure 3 Receiver operating characteristic curves of Bispectral index, mean dominant frequency, relative powers of electroencephalogram frequencies, and magnetic resonance spectroscopy peak values in predicting minimal hepatic encephalopathy. A: Bispectral index [area under the receiver operating characteristic (AUROC: 0.911)], mean dominant frequency (AUROC: 0.876), beta (AUROC: 0.876), alpha (AUROC: 0.876), delta (AUROC: 0.876), theta (AUROC: 0.886), myoinositol (AUROC: 0.911), choline (AUROC: 0.876), glutamine (AUROC: 0.886); B: Grade 1 hepatic encephalopathy [Bispectral index (AUROC: 0.911)], mean dominant frequency (AUROC: 0.876), beta (AUROC: 0.876), alpha (AUROC: 0.876), delta (AUROC: 0.876), theta (AUROC: 0.886), myoinositol (AUROC: 0.739), choline (AUROC: 0.681), glutamine (AUROC: 0.741). BIS: Bispectral index; MDF: Mean dominant frequency.

Figure 4 Kaplan-Meier curves comparing no hepatic encephalopathy, minimal hepatic encephalopathy, and grade 1 hepatic encephalopathy for overall survival, progression of hepatic encephalopathy (≥ 2) free survival, complications-free survival, and hospitalization-free survival. HE: Hepatic encephalopathy.

Figure 5 Independent risk factors for complications, hepatic encephalopathy progression (≥ grade 2), hospitalization, and mortality on multivariate analysis. HE: Hepatic encephalopathy; MELD: Model for end-stage liver disease; EEG: Electroencephalogram; IL: Interleukin; BIS: Bispectral index; CFF: Critical flicker frequency.