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

Table 4 Univariate and multivariate regression analysis to identify significant risk factors of progression of hepatic encephalopathy (hepatic encephalopathy ≥ grade 2)

Parameters	Univariate hazard ratio by the Cox regression model		Multivariate hazard ratio
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.009 (0.986-1.032)	0.441
Hemoglobin	1.005 (0.888-1.138)	0.937
TLC	1.000 (1.000-1.000)	0.055
Platelets	1.000 (1.000-1.000)	0.163
Blood urea	1.019 (1.000-1.038)	0.056
Creatinine	3.800 (1.760-8.208)	0.0007	1.293 (0.431-3.880)	0.646
Total protein	0.634 (0.475-0.845)	0.002	0.951 (0.647-1.399)	0.800
Serum albumin	0.497 (0.315-0.784)	0.003	1.123 (0.590-2.139)	0.724
Total bilirubin	1.092 (1.043-1.144)	0.0002	0.924 (0.825-1.034)	0.169
AST	1.006 (1.003-1.008)	0.0002	1.004 (0.999-1.008)	0.523
ALT	1.003 (0.998-1.009)	0.221
ALP	1.002 (0.99-1.005)	0.279
Na	0.945 (0.901-0.992)	0.022	0.969 (0.914-1.028)	0.294
K	0.981 (0.625-1.540)	0.934
INR	1.925 (1.390-2.664)	0.0001	0.443 (0.202-0.969)	0.041
Serum ammonia	1.010 (1.004-1.017)	0.001	0.996 (0.985-1.008)	0.523
CFF	0.909 (0.862-0.959)	0.0004	0.942 (0.855-1.039)	0.232
MELD	1.122 (1.083-1.161)	< 0.0001	1.211	< 0.0001
Myoinositol peak	0.059 (0.015-0.234)	0.0001	0.284 (0.023-3.549)	0.329
Choline peak	0.211 (0.069-0.645)	0.006	0.687 (0.165-2.858)	0.606
Glutamine peak	2.227 (1.244-3.986)	0.007	0.740 (0.287-1.904)	0.532
TNF-α	1.012 (1.005-1.020)	0.002	0.997 (0.981-1.012)	0.668
IL-6	1.005 (1.001-1.010)	0.012	0.998 (0.991-1.004)	0.521
IL-18	1.001 (1.000-1.003)	0.014	1.000 (0.997-1.003)	0.972
Endotoxin	58.094 (6.844-493.151)	0.0002	0.731 (0.000-1717.320)	0.937
IL-10	1.149 (1.075-1.229)	< 0.0001	1.122 (0.906-1.388)	0.291
IL-12	1.089 (1.038-1.142)	0.0004	0.786 (0.623-0.990)	0.041
IL-1β	1.116 (1.057-1.179)	0.0001	1.142 (0.926-1.410)	0.215
Gender
Female	1
Male	1.357 (0.647-2.844)	00.419
CTP grade
A	1
B	1.46E+03 (0.000-1.20E+71)	0.927
C	5.57E+03 (0.000-4.57E+71)	0.914
Grade of HE
No HE	1
Minimal HE	2.783 (1.330-5.822)	0.007	1.499 (0.327-6.878)	0.603
Grade 1 HE	4.200 (2.056-8.580)	0.0001	2.23	00.02

HR: Hazard ratio; CI: Confidence interval; TLC: Total leukocyte count; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; CFF: Critical flicker frequency; MELD: Model for end-stage liver disease; TNF: Tumor necrosis factor; IL: Interleukin; CTP: Child Turcotte Pugh; HE: Hepatic encephalopathy.