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

Table 1 Baseline characteristics, n (%)/mean ± SD

Characteristic	No HE (n = 50)	Minimal HE (n = 50)	Grade 1 HE (n = 50)	P value
Age, years	44.28 ± 9.15	46.7 ± 11.02	44.18 ± 11.29	0.401
Gender, male	41 (82)	42 (84)	45 (90)
Etiology
Alcohol	18 (36)	17 (34)	26 (52)	0.264
MASLD	9 (18)	10 (20)	5 (10)
HBV	3 (6)	10 (20)	4 (8)
Idiopathic	5 (10)	3 (6)	4 (8)
HCV	4 (8)	2 (4)	4 (8)
Others	11 (22)	8 (16)	7 (14)
Baseline investigations
Hemoglobin (g/dL)	9.32 ± 2.17	8.81 ± 1.62	8.91 ± 1.86	0.363
TLC (cells/μL)	5612.6 ± 2970	6606 ± 4144	7804 ± 6057	0.582
Platelet count (cells/μL)	97180 ± 67191	100240 ± 47215	100200 ± 53333	0.549
Blood urea (mg/dL)	31.58 ± 11.15	37.24 ± 12.95	38.26 ± 12.63	0.015
Serum creatinine (mg/dL)	0.89 ± 0.23	1.02 ± 0.25	1.03 ± 0.3	0.013
Total protein (g/dL)	7.4 ± 0.66	6.82 ± 0.67	6.65 ± 0.91	< 0.001
Serum albumin (g/dL)	3.3 ± 0.57	2.86 ± 0.49	2.79 ± 0.51	< 0.001
Total bilirubin (mg/dL)	2.14 ± 2.26	4.1 ± 3.74	4.42 ± 3.89	< 0.001
AST (U/L)	86.14 ± 82.93	89.64 ± 40.5	110.8 ± 76.02	0.005
ALT (U/L)	46.3 ± 54.15	43.54 ± 18.73	49.84 ± 31.1	0.188
ALP (U/L)	157.96 ± 56.93	161.82 ± 86.38	160.52 ± 62.11	0.943
Sodium (mEq/L)	134.66 ± 5.02	133.54 ± 5.09	131.9 ± 4.59	0.02
Potassium (mEq/L)	4.15 ± 0.42	4.16 ± 0.62	4.15 ± 0.62	0.997
INR	1.23 ± 0.21	1.48 ± 0.37	1.65 ± 0.55	< 0.001
Serum ammonia (μg/dL)	87.18 ± 19.12	123.42 ± 19.97	164.08 ± 30.12	< 0.001
Baseline prognostic scores, PHES and CFF
MELD	11.28 ± 3.17	15.8 ± 4.36	17.58 ± 5.8	0.001
CTP score	7.9 ± 1.09	10.3 ± 1.56	11.16 ± 1.5	0.001
CTP grade (A/B/C), n	1/44/5	0/12/38	0/7/43	0.001
PHES, median (interquartile range)	-1 (-2 to 1)	-5 (-6 to -5)	-8 (-9 to -7)	< 0.001
CFF (Hz)	42.82 ± 2.99	37.52 ± 2.07	34 ± 3.55	< 0.001
Inflammatory markers
TNF-α (pg/mL)	25.33 ± 10.81	47.08 ± 13.99	64.31 ± 28,39	< 0.001
IL-6 (pg/mL)	22.68 ± 16.79	69.92 ± 42.23	113.92 ± 46.13	< 0.001
IL-18 (pg/mL)	171.53 ± 61.58	348.01 ± 86.26	519.41 ± 178.71	< 0.001
Endotoxin (EU/mL)	0.37 ± 0.05	0.47 ± 0.04	0.6 ± 0.05	< 0.001
IL-10 (pg/mL)	8.19 ± 2.19	13.72 ±2	16.43 ± 1.86	< 0.001
IL-12 (pg/mL)	6.9 ± 2.23	12.97 ± 2.11	17.77 ± 2.74	< 0.001
IL-1β (pg/mL)	5.1 ± 15.6	10.62 ± 1.81	14.95 ± 2.27	< 0.001
MRS peaks
Myoinositol (mmol/L), median (interquartile range)	0.1 (0.02-0.2)	-0.11 (-0.2 to -0.08)	-0.2 (-0.3 to -0.16)	< 0.001
Choline (mmol/L)	0.71 ± 0.18	0.42 ± 0.18	0.38 ± 0.33	< 0.001
Glutamine (mmol/L)	0.41 ± 0.15	0.73 ± 0.23	1.01 ± 0.38	< 0.001
Bispectral index
Bispectral index value	91.18 ± 3.43	81.48 ± 3.9	72.9 ± 5.49	< 0.001
Spectral EEG analysis
MDF (Hz)	12.9 ± 4.66	7.89 ±1.19	5.13 ± 1.57	< 0.001
Relative power of frequency bands
Beta (%)	24.54 ± 8.73	12.76 ± 5.97	10.3 ± 5.91	< 0.001
Alpha (%)	48.5 ± 13.16	24 ± 10.6	16 ± 8.15	< 0.001
Theta (%)	11.6 ± 4.34	30.08 ± 12.98	24.7 ±12.9	< 0.001
Delta (%)	13.74 ± 6.73	31.42 ± 14.23	46.96 ± 17.56	< 0.001
Grade of EEG alteration
Grade 0	50 (100)	23 (46)	3 (6)	< 0.001
Grade 1	0 (0)	11 (22)	0 (0)
Grade 2	0 (0)	12 (24)	17 (34)
Grade 3	0 (0)	4 (8)	30 (60)

HE: Hepatic encephalopathy; MASLD: Metabolic dysfunction-associated steatotic liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; TLC: Total leukocyte count; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; MELD: Model for end-stage liver disease; CTP: Child Turcotte Pugh; PHES: Psychometric hepatic encephalopathy score; CFF: Critical flicker frequency; TNF: Tumor necrosis factor; IL: Interleukin; MRS: Magnetic resonance spectroscopy; EEG: Electroencephalogram; MDF: Mean dominant frequency.