Establish and validate an artificial neural networks model used for predicting portal vein thrombosis risk in hepatitis B-related cirrhosis patients

Table 1 Basic clinical characteristics of patients with hepatitis B virus-related cirrhosis, n (%)/mean (25^th-75^th percentiles)

Variables	All patients (n = 912)	Training cohort (n = 637)	Validation cohort (n = 275)	P value
Age, years	53.0 (41.0-73.0)	52.8.0 (40.0-74.0)	52.9 (43.0-75.0)	0.436
Male sex	611 (67.0)	439 (69.0)	172 (62.5)	0.320
Smoking	210 (23.0)	149 (23.4)	61 (22.2)	0.846
Alcohol consumption	195(21.4)	123 (19.3)	62 (22.5)	0.579
Diabetes	152 (16.7)	103 (16.2)	49 (17.8)	0.174
Hypertension	129 (14.1)	95 (14.9)	34 (12.4)	0.835
Ascites	197 (21.6)	134 (21.0)	63 (22.9)	0.485
Encephalopathy	41 (4.5)	30 (4.7)	11 (4.0)	0.458
Gastrointestinal varices with bleeding	134 (14.7)	88 (13.8)	46 (16.7)	0.348
HBeAg positivity	365 (40.0)	253 (39.9)	112 (40.7)	0.115
CTP score	7.0 (5.0-10.0)	7.0 (6.0-9.0)	7.0 (5.0-10.0)	0.626
MELD score	10.1 (7.8-12.9)	10.1 (8.0-12.6)	10.1 (7.7-13.6)	0.851
Alanine aminotransferase (U/L)	41.3 (26.5-105.8)	43.6 (27.1-112.4)	37.5 (25.1-95.5)	0.164
Aspartate aminotransferase (U/L)	47.9 (30.8-106.1)	48.6 (32.1-107.9)	46.7 (29.7-98.1)	0.282
Total bilirubin (μmol/L)	22.4 (14.2-39.2)	22.7 (14.1-38.5)	22.3 (14.5-40.7)	0.805
Albumin (g/L)	33.6 (30.3-39.2)	33.8 (30.4-40.1)	33.2 (30.1-38.4)	0.258
Gamma-glutamyl transpeptidase (U/L)	56.3 (37.2-97.8)	55.3 (36.1-99.7)	57.3 (40.4-95.6)	0.497
White blood cell count (× 109/L)	3.9 (2.8-5.3)	3.9 (2.8-5.3)	3.8 (2.7-5.3)	0.451
Neutrophil count (× 109/L)	2.2 (1.5-3.1)	2.2 (1.5-3.2)	2.2 (1.5-3.0)	0.434
Lymphocyte count (× 109/L)	1.1 (0.8-1.6)	1.1 (0.8-1.6)	1.1 (0.7-1.6)	0.921
Neutrophil-lymphocyte ratio	2.0 (1.4-2.7)	2.0 (1.4-2.8)	1.9 (1.4-2.6)	0.598
Platelets (× 109/L)	87.0 (65.8-118.6)	87.0 (65.0-116.0)	89.0 (67.0-121.0)	0.199
Creatinine (μmol/L)	66.0 (56.0-76.0)	66.1 (56.1-76.2)	65.0 (56.0-73.9)	0.602
Blood urea nitrogen (mmol/L)	5.1 (4.0-6.7)	5.1 (4.0-6.7)	5.2 (4.1-6.7)	0.717
Prothrombin time (s)	14.3 (12.7-16.3)	14.3 (12.8-16.1)	14.1 (12.5-16.7)	0.801
Prothrombin activity (%)	67.0 (54.0-80.0)	67.0 (54.0-80.0)	67.0 (53.0-81.0)	0.944
International normalized ratio	1.2 (1.1-1.3)	1.2 (1.1-1.3)	1.2 (1.1-1.4)	0.865
Width of portal vein, mm	7.1 (3.4-30.1)	7.2 (3.4-30.5)	6.7 (3.3-26.0)	0.375
HBV DNA (log 10IU/mL)	2.7(1.2-5.9)	2.7(1.2-5.8)	2.7(1.2-6.0)	0.340
NA(s) ETV/TDF	614/298	421/216	193/82	0.783
3-year PVT	167(18.3)	121(19.0)	46(16.7)	0.202
5-year PVT	217(23.8)	151(23.7)	66(24.0)	0.172

MELD: Model for end-stage liver disease; CTP: Child-Turcotte-Pugh; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; ALB: Albumin; WBC: White blood cells; NLR: Neutrophil–lymphocyte ratio; PLT: Platelet count; Cr: Creatinine; INR: International normalized ratio; NA(s): Nucleos(t)ide analogues; ETV: Entecavir; TDF: Tenofovir.

Table 2 Factors associated with prediction incidence of portal vein thrombosis

Variables	Univariate analysis		P value
	β	HR (95%CI)
Age (year)	0.044	1.045 (1.029-1.061)	< 0.001
Sex (male)	0.267	1.306 (0.873-1.954)	0.194
Smoking	0.081	0.922 (0.605-1.405)	0.706
Alcohol consumption	0.161	1,175 (0.767-1.800)	0.458
Diabetes	0.255	1.291 (0.807-2.064)	0.287
Ascites	0.660	1.935 (1.354-2.766)	< 0.001
Hepatic encephalopathy	0.255	1.291 (0.807-2.064)	0.287
Gastrointestinal varices with bleeding	0.767	2.153 (1.420-3.265)	< 0.001
Alanine aminotransferase (U/L)	-0.002	0.998 (0.996-0.999)	0.004
Aspartate aminotransferase (U/L)	-0.002	0.998 (0.996-0.999)	0.323
Total bilirubin (mg/dL)	-0.003	0.997 (0.992-1.001)	0.114
Albumin (g/L)	-0.029	0.972 (0.947-0.997)	0.028
gamma-glutamyl transpeptidase (U/L)	0.001	1.001 (0.998-1.003)	0.637
White blood cell count (× 109/L)	-0.007	0.993 (0.913-1.079)	0.861
NLR	0.286	1.331 (1.262-1.403)	< 0.001
Platelets (× 109/L)	-0.022	0.979 (0.972-0.985)	< 0.001
Creatinine (μmol/L)	0.001	1.001 (0.995-1.007)	0.758
International normalized ratio	0.559	1.749 (0.936-3.268)	0.080
Width of portal vein	-0.002	0.998 (0.996-1.000)	0.063
HBeAg positivity	0.726	1.242 (0.681–2.267)	0.487
HBV DNA (log 10IU/mL)	0.828	1.237 (0.677–2.244)	0.567
NA(s) ETV/TDF	0.925	1.245 (0.755–1.956)	0.789

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; ALB: Albumin; WBC: White blood cells; HBeAg: Hepatitis B e-antigen; NLR: Neutrophil–lymphocyte ratio; PLT: Platelet count; Cr: Creatinine; INR: International normalized ratio; NA(s): Nucleos(t)ide analogues; ETV: Entecavir; TDF: Tenofovir.

Table 3 Positive predictive and negative predictive values, 95%CI

Cohort	Models	3-year risk of PVT		5-year risk of PVT
		Positive (%)	Negative (%)	Positive (%)	Negative (%)
Training cohort	ANN (low risk)	26.2 (25.0-27.4)	98.7 (95.2-99.7)	23.2 (21.0-28.4)	97.7 (95.2-99.7)
	ANN (high risk)	54.7 (48.6-60.7)	98.6 (89.4-99.4)	52.7 (49.6-60.7)	98.6 (88.4-99.5)
Validation cohort	ANN (low risk)	20.9 (19.6-22.2)	100 (-)	19.9 (19.6-24.2)	97.9 (89.6-98.3)
	ANN (high risk)	41.5 (32.8-50.8)	91.9 (88.6-94.3)	31.5 (28.8-51.8)	98.9 (88.6-99.3)

PVT: Portal vein thrombosis; ANN: Artificial neural network.

Table 4 Comparison of performance and discriminative ability among the current model and other models, 95%CI

Cohort	Models	3-year risk of PVT			5-year risk of PVT
		AUROC	C-index	P value	AUROC	C-index	P value
Training cohort	ANN	0.967 (0.960-0.974)	0.954		0.975 (0.955–0.992)	0.958
	CTP	0.593 (0.568-0.618)	0.591	< 0.001	0.602 (0.579-0.625)	0.592	< 0.001
	MELD	0.530 (0.550-0.560)	0.535	< 0.001	0.555 (0.528-0.581)	0.544	< 0.001
Validation cohort	ANN	0.958 (0.944–0.973)	0.941		0.973 (0.958–0.987)
	CTP	0.541 (0.497-0.585)	0.552	< 0.001	0.547 (0.508-0.585)	0.541	< 0.001
	MELD	0.539 (0.492-0.586)	0.544	< 0.001	0.553 (0.512-0.594)	0.546	< 0.001

PVT: Portal vein thrombosis; AUROC: Area under the receiver operating characteristic curve; CTP: Child-Pugh-Turcotte; MELD: Model for end-stage liver disease; ANN: Artificial neural network.