Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

Table 1 Baseline characteristics and outcomes of patients

Characteristic	Derivation cohort (n = 322)	Missing data in derivation cohort (%)	Validation cohort (n = 155)	Missing data in validation cohort (%)	P value
Demographics
Age (year)	58.38 ± 11.86	0	57.7 ± 13.37	0	0.57
Sex, n (%)		0		0	0.36
Female	132 (40.99)		56 (36.13)
Male	190 (59.01)		99 (63.87)
Smoking history, n (%)	52 (16.25)	0.6	26 (16.77)	0	0.99
Drinking history, n (%)	74 (23.12)	0.6	30 (19.35)	0	0.42
Surroundings, n (%)		0		0	0.67
Rural	93 (28.88)		50 (32.26)
Suburban	58 (18.01)		24 (15.48)
Urban	171 (53.11)		81 (52.26)
Symptom, n (%)		0		0	0.44
Melena or hematochezia	115 (35.71)		49 (31.61)
Hematemesis	207 (64.29)		106 (68.39)
Etiology, n (%)		0		0	0.8
Chronic HBV infection	156 (48.45)		69 (44.52)
Autoimmune liver disease	55 (17.08)		31 (20.00)
Alcohol-related	50 (15.53)		23 (14.84)
Other	61 (18.94)		32 (20.65)
Course of cirrhosis (year)	2 (0.5-6)	3.7	2 (0.2-6)	0	0.46
Family history of cirrhosis, n (%)	52 (16.20)	0.3	7 (4.52)	0	< 0.01
Endoscopic treatment and presentation
Received emergency endoscopic hemostasis, n (%)	28 (8.70)	0	10 (6.45)	0	0.5
Types of varices, n (%)		0		0	< 0.01
EV	177 (54.97)		28 (18.06)
EV combined with GV	145 (45.03)		127 (81.94)
Red color sign, n (%)	302 (93.79)	0	150 (96.77)	0	0.25
Bleeding signs, n (%)	49 (15.22)	0	29 (18.71)	0	0.4
Form of varices, n (%)		0		0	0.57
F1	56 (17.39)		23 (14.84)
F2-F3	266 (82.61)		132 (85.16)
Location of varices, n (%)		0.3		0	< 0.01
Low to middle	252 (78.50)		146 (94.19)
High	69 (21.50)		9 (5.81)
Numbers of varices	4 (4-4)		4 (4-4)		0.73
Diameter of varices (cm)	0.9 (0.8-1)	0.6	1 (0.8-1)	0	0.53
Number of EVL (times)	2 (1-3)	0	2 (1.5-3)	0	0.05
Received sclerotherapy injections, n (%)	139 (43.17)	0	74 (47.74)	0	0.4
Received tissue glue injections, n (%)	125 (38.82)	0	65 (41.94)	0	0.58
Comorbidities and complications
Ascites, n (%)	220 (68.32)	0	95 (61.29)	0	0.16
Bacterial infection, n (%)	48 (14.91)	0	12 (7.74)	0	0.04
Encephalopathy, n (%)	13 (4.04)	0	3 (1.94)	0	0.36
Diabetes, n (%)	67 (20.87)	0.3	31 (20.00)	0	0.92
Hypertension, n (%)	78 (24.30)	0.3	20 (12.90)	0	0.01
Hemorrhagic shock, n (%)	10 (3.12)	0.3	2 (1.29)	0	0.38
Heart disease, n (%)	16 (4.98)	0.3	7 (4.52)	0	1.00
Laboratory tests
Total bilirubin (μmol/L)	21.3 (15-32.02)	3.1	15.8 (10.85-20.85)	0	< 0.01
Alanine aminotransferase (U/L)	25 (17-36)	4.3	21 (15-30)	0	0.01
Aspartate aminotransferase (U/L)	35 (26-47)	4.3	28 (21-38.5)	0	< 0.01
Alkaline phosphatase (U/L)	87 (68-130)	5	83 (63.25-107)	0.6	0.05
Total protein (g/L)	62.45 ± 8.92	3.8	62.9 ± 9.16	0	0.62
Albumin (g/L)	31.89 ± 6.07	3.1	35.3 ± 5.94	0	< 0.01
Globulin (g/L)	29.55 (25.9-34.42)	5.6	27 (23-32)	0	< 0.01
A/G	1.05 (0.87-1.3)	5.6	1.33 (1.08-1.59)	0	< 0.01
Blood urea nitrogen (mmol/L)	5.72 (4.2-7.72)	6.8	5.2 (4.1-6.18)	0.6	< 0.01
Creatinine (μmoI/L)	65.4 (55-79)	4.7	69 (57.25-80.5)	0.6	0.14
Uric acid (μmoI/L)	298 (238-372)	4.7	288 (239-357)	0	0.26
Total cholesterol (mmol/L)	3.17 (2.61-3.94)	7.5	3.17 (2.6-3.94)	25.8	0.94
White blood cell (× 109/L)	3.1 (2.09-4.75)	5.6	2.66 (1.92-4.47)	0	0.07
Neutrophil (× 109/L)	1.96 (1.25-3.52)	5.3	1.6 (1.1-2.77)	0.6	< 0.01
Lymphocyte (× 109/L)	0.7 (0.5-1.03)	5.9	0.7 (0.5-1)	1.9	0.69
Red blood cell (× 109/L)	3.05 ± 0.74	3.4	3.19 ± 0.77	0	0.08
Hemoglobin (g/L)	88.37 ± 24.42	1.9	89.1 ± 22.33	0	0.76
Platelet count (× 109/L)	68 (45.75-91.25)	3.1	68 (45.5-103)	0	0.68
Prothrombin time (second)	14.8 (13.6-16.25)	3.4	14.4 (13.7-15.6)	0	0.07
INR (unit)	1.27 (1.15-1.4)	4	1.26 (1.17-1.37)	0	0.48
D-dipolymer (μg/mL)	1.45 (0.56-3.34)	7.1	1.1 (0.45-2.37)	1.9	0.12
Thrombin time (second)	17.8 (16.9-19.1)	6.5	17.8 (16.67-18.72)	1.9	0.34
Fibrinogen (g/L)	200.26 ± 80.04	5.6	185.67 ± 69.84	1.9	0.06
CTP (points)	7 (6-8)	0	6 (6-7)	0	< 0.01
CTP class, n (%)		0		0	< 0.01
A (5-6)	101 (31.37)		83 (53.55)
B (7-9)	190 (59.01)		69 (44.52)
C (10-13)	31 (9.63)		3 (1.94)
MELD (points)	11 (9-13)	0	9 (8-11)	0	< 0.01
Radiological features
Portal vein thrombosis, n (%)	68 (21.12)	1.2	49 (31.61)	0	0.02
Splenic vein diameter (mm)	9.6 ± 3.45	6.8	9.08 ± 3.94	4.5	0.16
Inner diameter of portal vein trunk (mm)	13.17 ± 2.34	6.5	12.7 ± 2.97	4.5	0.07
Use of medication
Use of NSBB, n (%)	314 (65.83)	0	204 (63.35)	0	0.12
Use of PPI, n (%)	450 (94.34)	0	306 (95.03)	0	0.47
Use of antibiotics, n (%)	335 (70.23)	0	219 (68.01)	0	0.16
Outcomes
Rebleeding within 6 weeks, n (%)	26 (8.07)	0	7 (4.52)	0	0.21
Rebleeding within 6 months, n (%)	60 (18.63)	0	22 (14.19)	0	0.28
Rebleeding within 1 year, n (%)	83 (25.78)	0	36 (23.23)	0	0.62
Rebleeding within 2 years, n (%)	111 (34.47)	0	51 (32.90)	0	0.81
Follow-up time (day)	408.5 (322-885)	0	447 (366-1108)	0	0.06

EV: Esophageal varices; GV: Gastric varices; EVL: Endoscopic variceal ligation; INR: International normalized ratio; A/G: Albumin/globulin; CTP: Child-Turcotte-Pugh score; MELD: Model for end-stage liver disease score; NSBB: Non-selective beta-blockers; PPI: Proton pump inhibitor.

Table 2 Predictive performance of the rebleeding event prediction following endoscopic treatment model

	C-index	AUC (95%CI)	Brier (95%CI)
The derivation cohort
6 weeks	85.7	0.856 (0.794-0.918)	0.062 (0.042-0.083)
1 year	77.5	0.796 (0.737-0.855)	0.143 (0.121-0.165)
2 years	74.1	0.790 (0.727-0.853)	0.177 (0.149-0.205)
Internal validation
6 weeks	84.2	0.841 (0.755-0.925)	0.066 (0.036-0.102)
1 year	75.9	0.783 (0.712-0.842)	0.153 (0.127-0.185)
2 years	73.5	0.779 (0.685-0.867)	0.184 (0.146-0.233)
External validation
6 weeks	88.5	0.803 (0.647-0.959)	0.04 (0.014-0.066)
1 year	86.2	0.868 (0.808-0.928)	0.127 (0.096-0.159)
2 years	76.8	0.733 (0.634-0.832)	0.194 (0.151-0.237)

C-index: Concordance index; AUC: Area under the receiver operating curve; CI: Confidence interval.

Table 3 Model performance in sensitivity analysis and subgroup analyses

	C-index	AUC (95%CI)	Brier score (95%CI)
Sensitivity analysis
Exclude patients underwent emergency endoscopy
6 weeks	0.847	0.847 (0.781-0.913)	0.053 (0.036-0.07)
1 year	0.78	0.8 (0.749-0.85)	0.136 (0.117-0.156)
2 years	0.724	0.75 (0.691-0.81)	0.188 (0.163-0.213)
Subgroup analysis
Etiology of cirrhosis
Chronic HBV infection
6 weeks	0.9	0.915 (0.858-0.973)	0.04 (0.021-0.059)
1 year	0.779	0.793 (0.718-0.867)	0.137 (0.11-0.164)
2 years	0.717	0.731 (0.646-0.816)	0.195 (0.158-0.232)
Autoimmune liver disease
6 weeks	0.913	0.884 (0.761-1)	0.048 (0.011-0.085)
1 year	0.84	0.892 (0.814-0.97)	0.122 (0.083-0.162)
2 years	0.798	0.821 (0.69-0.953)	0.154 (0.103-0.206)
Alcohol-related
6 weeks	0.803	0.817 (0.705-0.929)	0.093 (0.04-0.147)
1 year	0.786	0.828 (0.723-0.934)	0.138 (0.094-0.183)
2 years	0.757	0.783 (0.66-0.907)	0.174 (0.126-0.222)
Other
6 weeks	0.745	0.718 (0.532-0.903)	0.067 (0.025-0.109)
1 year	0.812	0.793 (0.695-0.892)	0.153 (0.11-0.196)
2 years	0.743	0.777 (0.658-0.897)	0.2 (0.141-0.259)
Types of varices
EV
6 weeks	0.862	0.868 (0.796-0.94)	0.061 (0.036-0.087)
1 year	0.836	0.854 (0.799-0.909)	0.129 (0.103-0.155)
2 years	0.776	0.822 (0.747-0.896)	0.164 (0.131-0.197)
EV combined with GV
6 weeks	0.845	0.823 (0.727-0.919)	0.05 (0.029-0.071)
1 year	0.768	0.791 (0.726-0.857)	0.144 (0.119-0.17)
2 years	0.715	0.726 (0.65-0.802)	0.203 (0.169-0.237)
Sex
Male
6 weeks	0.872	0.894 (0.845-0.943)	0.062 (0.04-0.084)
1 year	0.796	0.809 (0.75-0.869)	0.139 (0.115-0.163)
2 years	0.719	0.724 (0.651-0.798)	0.2 (0.167-0.234)
Female
6 weeks	0.703	0.71 (0.539-0.882)	0.044 (0.02-0.067)
1 year	0.781	0.831 (0.764-0.899)	0.136 (0.108-0.164)
2 years	0.772	0.831 (0.756-0.907)	0.164 (0.13-0.197)
Age
< 60
6 weeks	0.889	0.862 (0.77-0.954)	0.046 (0.025-0.067)
1 year	0.771	0.783 (0.711-0.854)	0.134 (0.107-0.161)
2 years	0.706	0.731 (0.649-0.812)	0.191 (0.155-0.227)
≥ 60
6 weeks	0.814	0.826 (0.742-0.909)	0.064 (0.039-0.089)
1 year	0.801	0.848 (0.792-0.904)	0.142 (0.117-0.166)
2 years	0.761	0.796 (0.723-0.87)	0.181 (0.150-0.213)
Use of NSBB
Non-NSBB group
6 weeks	0.846	0.837 (0.753-0.921)	0.079 (0.046-0.113)
1 year	0.802	0.835 (0.762-0.908)	0.146 (0.114-0.178)
2 years	0.794	0.871 (0.805-0.937)	0.141 (0.11-0.171)
NSBB group
6 weeks	0.85	0.846 (0.754-0.939)	0.042 (0.025-0.06)
1 year	0.79	0.806 (0.75-0.862)	0.134 (0.112-0.156)
2 years	0.708	0.705 (0.631-0.78)	0.21 (0.177-0.242)

C-index: Concordance index; AUC: Area under the receiver operating curve; CI: Confidence interval; HBV: Hepatitis B virus; EV: Esophageal varices; GV: Gastric varices; NSBB: Nonselective beta-blocker.