Predicting disease progression in cirrhotic patients after transjugular intrahepatic portosystemic shunt implantation: A sex-stratified analysis

Table 1 Patient characteristics in the cohorts

Variable	All (n = 186)	Male (n = 142)			Female (n = 42)
		Transplantation-free survival (n = 115)	Progression (n = 27)	P value	Transplantation-free survival (n = 34)	Progression (n = 10)	P value
Age (yr)	51 (44-57)	48.0 (43.0-53.0)	56.0 (45.0-63.0)	0.017	55.0 (47.0-62.0)	64.0 (62.0-66.0)	0.001
BMI (kg/m2)	23.0 (21.4-24.0)	23.0 (21.7-24.3)	23.0 (20.8-23.0)	0.098	22.1 (21.4-23.5)	21.9 (19.4-23.7)	0.73
SMI (cm2/m2)	38.9 (31.2-45.3)	41.9 (36.6-48.1)	37.6 (30.8-44.2)	0.036	29.4 (25.4-33.4)	28.68 (26.49-35.36)	0.901
SATI (cm2/m2)	27.1 (14.1-45.6)	24.8 (13.1-38.6)	20.9 (10.4-36.5)	0.252	43.79 (19.23-55.96)	51.51 (32.58-81.8)	0.128
VATI (cm2/m2)	37.6 (24.5-49.7)	37.3 (22.7-53.1)	39.0 (24.8-48.1)	0.592	32.45 (24.58-41.92)	39.90 (34.25-69.58)	0.075
MELD score	9.0 (6.0-12.0)	8.0 (5.0-11.0)	11.0 (7.0-14.0)	0.070	9.0 (6.0-12.0)	10.0 (9.75-11.25)	0.354
CTP score	7.0 (6.0-9.0)	7.0 (6.0-9.0)	9.0 (7.0-9.0)	0.014	7.5 (6.0-8.0)	7.0 (6.0-8.0)	0.572
CTP classification				0.148			0.513
A (%)	55 (29.6)	38 (33.0)	4 (14.8)		10 (20.4)	3 (30.0)
B (%)	113 (60.8)	67 (58.3)	19 (70.4)		20 (58.8)	7 (70.0)
C (%)	18 (9.7)	10 (8.7)	4 (14.8)		4 (11.8)	0 (0)
Etiology (%)				0.051			0.09
HBV/HCV	104 (55.9)	69 (60.0)	12 (44.4)		20 (58.8)	3 (30.0)
Alcohol	51 (27.4)	40 (34.8)	10 (37.0)		1 (2.9)	0 (0)
Others	31 (16.7)	6 (5.2)	5 (18.6)		13 (38.2)	7 (70.0)
Ascites (%)				0.43			0.993
None	48 (25.8)	28 (24.3)	4 (14.8)		12 (35.3)	4 (40.0)
Mild	51 (27.4)	35 (30.4)	7 (25.9)		7 (20.6)	2 (20.0)
Moderate	45 (24.2)	29 (25.2)	7 (25.9)		7 (20.6)	2 (20.0)
Massive	42 (22.6)	23 (20.0)	9 (33.3)		8 (23.5)	2 (20.0)
Portal vein thrombosis (%)	37 (19.9)	23 (20.0)	6 (22.2)	0.797	8 (23.5)	0 (0)
Portal vein pressure (mm Hg)	32.0 (28.0-36.8)	32.3 (28.4-36.9)	33.8 (30.1-38.4)	0.141	30.5 (24.4-33.1)	30.5 (27.0-32.3)	0.553
Albumin (g/L)	30.45 (26.80-33.90)	30.85 (26.95-33.93)	28.60 (24.90-30.80)	0.041	31.05 (27.33-34.68)	29.90 (23.43-33.45)	0.464
International normalized ratio	1.28 (1.16-1.38)	1.29 (1.18-1.37)	1.34 (1.15-1.50)	0.295	1.23 (1.07-1.37)	1.18 (1.13-1.38)	0.61
Total bilirubin (mol/L)	22.60 (14.90-31.65)	20.7 (13.6-29.9)	28.3 (12.6-43.6)	0.236	24.15 (17.88-37.18)	28.35 (22.20-32.68)	0.649
Creatinine (mol/L)	70.5 (59.0-82.3)	72.55 (62.38-83.18)	79.60 (64.80-114.10)	0.069	57.05 (49.75-65.88)	58.50 (51.50-80.00)	0.499
Sodium (mmol/l)	138.45 (136.0-140.8)	138.25 (136.00-140.48)	138.20 (135.00-141.00)	0.985	139.00 (135.75-140.85)	139.00 (133.90-140.80)	0.585
Alanine aminotransferase (U/L)	21.0 (15.0-32.3)	21.0 (15.0-30.0)	24.0 (14.0-45.0)	0.274	19.5 (15.8-32.8)	28.4 (22.2-32.7)	0.989
Plasma ammonia (mol/L)	47.8 (34.7-54.6)	44.84 (33.80-49.20)	50.56 (44.40-69.07)	0.005	47.80 (34.46-54.84)	48.18 (46.20-62.12)	0.354
White blood cells (× 109/L)	3.76 (2.60-5.66)	3.71 (2.60-5.50)	4.78 (3.20-8.44)	0.108	3.32 (2.17-5.55)	3.79 (3.07-6.22)	0.312
Platelets (× 109/L)	64.5 (46.0-91.3)	65.0 (47.0-92.0)	70.0 (49.0-92.0)	0.888	66.0 (46.5-83.5)	51.5 (39.0-80.8)	0.354
Neutrophils (× 109/L)	2.60 (1.58-4.23)	2.49 (1.61-3.99)	3.93 (2.12-6.79)	0.048	2.11 (1.34-4.00)	2.66 (2.28-5.03)	0.273
Lymphocytes (× 109/L)	0.67 (0.49-0.97)	0.68 (0.49-0.96)	0.65 (0.46-1.08)	0.944	0.64 (0.54-1.09)	0.52 (0.40-0.78)	0.108
NLR	3.45 (2.52-5.79)	3.38 (2.41-5.64)	5.22 (3.16-7.28)	0.046	2.70 (1.99-4.50)	6.38 (3.97-8.59)	0.001
PLR	94.25 (67.80-133.51)	95.39 (68.91-133.33)	86.36 (64.12-153.33)	0.670	100.00 (67.18-127.60)	101.80 (78.06-149.53)	0.591
Alpha-fetoprotein, mmol/L	4.10 (2.19-5.36)	4.09 (2.10-5.36)	3.92 (2.40-5.36)	0.796	3.48 (2.07-5.36)	5.36 (5.36-5.53)	0.016

Continuous variables are presented as median in the absence of normal distribution. Categorical variables are presented as absolute value and relative frequency [n (%)]. Differences in continuous variables were calculated using Mann-Whitney U test and differences in categorical variables were assessed using the chi-square test. BMI: Body mass index; SMI: Skeletal muscle index; SATI: Subcutaneous adipose tissue index; VATI: Visceral adipose tissue index; MELD: Model of end-stage liver disease; CTP: Child-Turcotte-Pugh; HBV: Hepatitis B virus; HCV: Hepatitis C virus; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio.

Table 2 Univariable and multivariable Cox regression analyses for prognostic factors in patients with transjugular intrahepatic portosystemic shunt implantation

Death or liver transplantation	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
All (n = 186)
Age (yr)	1.073 (1.039-1.108)	< 0.001
BMI	0.914 (0.814-1.026)	0.128
CTP score	1.212 (1.012-1.451)	0.037
Etiology (%)
HBV/HCV	Reference		Reference
Alcohol	1.421 (0.638-3.165)	0.39	1.205 (0.503-2.888)	0.675
Others	2.862 (1.337-6.125)	0.007	3.807 (1.680-8.623)	0.001
Creatinine (mol/L)	1.008 (1.005-1.012)	< 0.001	1.006 (1.002-1.011)	0.005
Plasma ammonia (mol/L)	1.027 (1.013-1.041)	< 0.001	1.025 (1.009-1.041)	0.003
Alpha-fetoprotein (mmol/L)	1.030 (1.017-1.044)	< 0.001	1.021 (1.005-1.036)	0.009
NLR	1.088 (1.036-1.142)	0.001
SMI < 32.8	2.250 (1.179-4.291)	0.014	2.192 (1.008-4.769)	0.048
Postoperative ACLF	2.927 (1.218-7.037)	0.016
Postoperative HE	10.115 (4.851-21.091)	< 0.001	8.721 (4.065-18.710)	< 0.001
Male (n = 142)
Age (yr)	1.062 (1.024-1.100)	0.001
BMI	0.897 (0.781-1.030)	0.897
CTP score	1.294 (1.069-1.566)	0.008
MELD score	1.122 (1.034-1.217)	0.006
Etiology (%)
HBV/HCV	Reference
Alcohol	1.453 (0.627-3.367)	0.384
Others	3.396 (1.193-9.670)	0.022
Creatinine (mol/L)	1.009 (1.005-1.013)	< 0.001	1.008 (1.004-1.013)	0.001
Plasma ammonia (mol/L)	1.028 (1.012-1.044)	< 0.001	1.028 (1.011-1.046)	0.001
Alpha-fetoprotein (mmol/L)	1.032 (1.015-1.049)	< 0.001
NLR	1.080 (1.018-1.146)	0.011
SMI < 32.8	3.275 (1.516-7.073)	0.003	3.277 (1.306-8.226)	0.011
Postoperative ACLF	10.066 (3.249-31.187)	< 0.001	5.621 (1.685-18.752)	0.005
Postoperative HE	6.697 (3.015-14.876)	< 0.001	5.110 (2.153-12.126)	< 0.001

Variable selection for the multivariable Cox regression model was performed using stepwise forward selection. CI: Confidence interval; HR: Hazard ratio; BMI: Body mass index; CTP: Child-Turcotte-Pugh; HBV: Hepatitis B virus; HCV: Hepatitis C virus; NLR: Neutrophil-to-lymphocyte ratio; SMI: Skeletal muscle index; ACLF: Acute-on-chronic liver failure; HE: Hepatic encephalopathy.

Table 3 Predictive performance of different models in the training set and test set

Model	Variable	Training set AUC (95%CI)	Sensitivity	Specificity	Test set AUC (95%CI)	Sensitivity	Specificity
Model 1	Creatinine, plasma ammonia, SMI, ACLF, HE	0.842 (0.763-0.921)	0.957	0.652	0.875 (0.672-1.000)	0.75	0.962
Model 2	Creatinine, plasma ammonia, SMI, ACLF, HE	0.864 (0.785-0.942)	0.864	0.707	0.809 (0.631-0.986)	1.000	0.609
Model 3	Creatinine, SMI, HE	0.804 (0.689-0.918)	0.857	0.674	0.768 (0.581-0.955)	0.833	0.696
Model 4	Creatinine, plasma ammonia, SMI, ACLF, HE	0.842 (0.761-0.923)	0.783	0.813	0.948 (0.844-1.00)	1.000	0.792
Model 5	Creatinine, plasma ammonia, SMI, HE	0.840 (0.760-0.921)	0.957	0.636	0.823 (0.659-0.987)	1.000	0.667

We used 5-fold cross-validation to classify male patients into five parts, among which four parts were used as the training set and one part as the validation set. AUC: Area under the receiver operating characteristic curve; CI: Confidence interval; SMI: Skeletal muscle index; ACLF: Acute-on-chronic liver failure; HE: Hepatic encephalopathy.