Modified model incorporating sarcopenia and myosteatosis for predicting severe hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: Multicenter study

Table 1 Demographic data, relevant clinical characteristics, and nutritional-muscular profiles of patients with cirrhosis in the training cohort and two validation cohorts, n (%)/median (interquartile range)/mean ± SD

Characteristics	All patients (n = 590)	Center I (n = 419)		Centers II, III, IV (n = 171)	P value
		Training cohort (n = 295)	Internal validation cohort (n = 124)	External validation cohort (n = 171)
Severe hepatic encephalopathy	108 (18.3)	57 (19.3)	21 (16.9)	30 (17.5)	0.808
Age (years)	54.00 (47.00, 62.00)	53.00 (47.00, 60.50)	55.00 (49.00, 65.00)	57.00 (51.00, 65.00)	0.230
Gender
Male	414 (70.2)	202 (68.5)	100 (80.6)	112 (65.5)	0.013
Female	176 (29.8)	93 (31.5)	24 (19.4)	59 (34.5)
Sarcopenia
No	410 (69.5)	208 (70.5)	89 (71.8)	113 (66.1)	0.500
Yes	180 (30.5)	87 (29.5)	35 (28.2)	58 (33.9)
Myosteatosis
No	348 (59.0)	162 (54.9)	65 (52.4)	121 (70.8)	< 0.001
Yes	242 (41.0)	133 (45.1)	59 (47.6)	50 (29.2)
Etiology
Viral hepatitis	338 (57.3)	171 (58.0)	71 (57.3)	96 (56.1)	0.929
Other	252 (42.7)	124 (42.0)	53 (42.7)	75 (43.9)
Ascites
No	187 (31.7)	88 (29.8)	41 (33.1)	58 (33.9)	0.615
Yes	403 (68.3)	207 (70.2)	83 (66.9)	113 (66.1)
Diabetes
No	490 (83.1)	242 (82.0)	109 (87.9)	139 (81.3)	0.263
Yes	100 (16.9)	53 (18.0)	15 (12.1)	32 (18.7)
Child-Pugh score	7.00 (6.00, 9.00)	7.00 (6.00, 9.00)	7.00 (6.00, 8.00)	7.00 (6.00, 8.00)	0.033
Meld score	10.00 (7.00, 12.00)	10.00 (7.00, 13.00)	10.00 (7.00, 12.00)	9.19 (7.26, 11.47)	0.796
Meld-Na score	10.20 (8.00, 14.00)	10.60 (8.00, 14.00)	10.00 (7.00, 13.00)	7.98 (4.00, 11.39)	< 0.001
Freiburg index of post-transjugular intrahepatic portosystemic shunt survival score	-1.04 (-1.65 to -0.47)	-1.07 (-1.65 to -0.48)	-0.96 (-1.63 to -0.44)	-0.90 (-1.50 to -0.01)
Prothrombin time (seconds)	15.00 (13.50, 16.80)	15.10 (13.55, 16.90)	14.90 (13.40, 16.42)	14.40 (12.93, 15.97)	0.058
Blood urea nitrogen (mmol/L)	5.85 (4.33, 8.10)	5.85 (4.33, 8.20)	5.85 (4.24, 7.84)	6.74 (4.73, 8.66)	0.040
Platelets (× 109)	67.00 (46.00, 106.00)	68.00 (48.00, 106.00)	65.50 (43.28, 103.25)	72.00 (51.00, 106.00)	0.195
Lymphocytes (× 109)	0.70 (0.45, 1.10)	0.70 (0.46, 1.18)	0.70 (0.44, 0.99)	0.70 (0.46, 1.00)	0.742
Hemoglobin (g/L)	80.00 (65.00, 99.50)	80.00 (65.00, 99.50)	80.50 (65.75, 98.50)	78.00 (65.00, 89.00)	0.062
Albumin (g/L)	32.60 (29.28, 36.20)	32.50 (29.00, 36.40)	32.65 (29.52, 35.52)	32.60 (29.50, 36.30)	0.876
Alanine aminotransferase (U/L)	22.00 (15.00, 33.00)	22.00 (15.00, 32.45)	23.00 (15.75, 35.70)	19.70 (14.00, 32.00)	0.431
Aspartate aminotransferase (U/L)	30.20 (22.50, 42.45)	30.00 (21.60, 42.45)	31.50 (24.00, 42.25)	27.60 (20.88, 42.91)	0.100
Creatinine (μmol/L)	63.00 (52.00, 78.00)	62.00 (52.00, 80.00)	66.00 (53.00, 75.00)	62.00 (51.50, 73.30)	0.388
Total bilirubin (μmol/L)	21.10 (14.10, 31.05)	21.10 (14.30, 31.95)	21.10 (13.88, 26.75)	18.04 (13.60, 25.79)	0.113
Maximal transverse diameter of the right psoas muscle at the L3 level (cm)	1.90 (1.52, 2.37)	1.89 (1.52, 2.33)	1.91 (1.54, 2.39)	1.87 (1.49, 2.47)	0.099
Cross-sectional area of the right psoas muscle at the L3 level (cm2)	5.49 (3.83, 7.02)	5.57 (3.78, 7.02)	5.39 (3.92, 7.00)	5.06 (3.50, 6.64)	0.012
Mean muscle attenuation in HU of the right psoas muscle at the L3 level (HU)	45.60 ± 10.17	44.14 ± 9.35	43.65 ± 10.47	49.54 ± 10.29	< 0.001
L3_transversal psoas muscle thickness-to-height (mm/m)	11.30 (9.41, 13.95)	11.30 (9.36, 13.85)	11.30 (9.56, 14.60)	11.33 (9.00, 14.11)	0.217
Time (months)	27.50 (14.00, 47.40)	26.53 (14.00, 47.70)	29.75 (14.50, 47.00)	21.50 (12.10, 24.30)	< 0.001

HU: Hounsfield units; L3: Third lumbar vertebra.

Table 2 Univariate and multivariate Cox regression analyses of severe hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis

Characteristics	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age (years)	1.042 (1.018-1.067)	< 0.001	-	-
Gender (female/male)	0.609 (0.328-1.131)	0.116	-	-
Sarcopenia (yes/no)	2.598 (1.545-4.370)	< 0.001	2.722 (1.596-4.641)	< 0.001a
Freiburg index of post-transjugular intrahepatic portosystemic shunt survival score	1.801 (1.349-2.405)	< 0.001	1.753 (1.266-2.428)	0.001a
Prothrombin time (seconds)	1.023 (0.930-1.124)	0.644	-	-
Blood urea nitrogen (mmol/L)	1.050 (1.013-1.089)	0.008	1.002 (0.957-1.049)	0.932
White blood cell (109/L)	0.941 (0.851-1.041)	0.237	-	-
Platelets (109/L)	0.997 (0.992-1.001)	0.156	-	-
Lymphocyte (109/L)	0.687 (0.424-1.112)	0.127	-	-
Hemoglobin (g/L)	1.003 (0.993-1.013)	0.542	-	-
Albumin (g/L)	0.968 (0.921-1.017)	0.2	-	-
Alanine aminotransferase (U/L)	1.004 (1.001-1.008)	0.022	1.004 (1.000-1.008)	0.085
Creatinine (μmol/L)	1.008 (1.003-1.013)	0.002	-	-
Total bilirubin (μmol/L)	1.015 (1.003-1.026)	0.013	-	-
Maximal transverse diameter of the right psoas muscle at the L3 level (cm)	0.594 (0.363-0.973)	0.038	-	-
Cross-sectional area of the right psoas muscle at the L3 level (cm2)	0.909 (0.802-1.031)	0.137	-	-
Mean muscle attenuation in HU of the right psoas muscle at the L3 level (HU)	0.964 (0.938-0.990)	0.007	-	-
Myosteatosis	2.245 (1.316-3.830)	0.003	1.921 (1.114-3.312)	0.019a
L3_transversal psoas muscle thickness-to-height (mm/m)	0.907 (0.832-0.988)	0.025	-	-

^aP < 0.05 in the multivariable analysis.

Full candidate variables before stepwise selection included: Freiburg index of post-transjugular intrahepatic portosystemic shunt survival score, sarcopenia, blood urea nitrogen, alanine aminotransferase, and myosteatosis. HR: Hazard ratio; L3: Third lumbar vertebra.

Table 3 Integrated discrimination improvement for the overall cohort and individual cohorts

Dataset	Integrated discrimination improvement	95%CI	P value
All cohorts	0.044	0.019-0.070	0.001
Training cohort	0.071	0.037-0.105	< 0.001
Internal validation cohort	0.047	-0.005 to 0.099	0.074
External validation cohort	0.093	0.034-0.152	0.002