Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization

Table 1 Baseline characteristic for the cohort, n = 792

Characteristics	Values
Age at start, yr, mean ± SD	56.4 ± 11.6
Gender, men/women, n (%)	663 (83.7)/129 (16.3)
Etiology, HBV/non-HBV, n (%)	681 (86.0)/111 (14.0)
Child-Pugh class, A/B, n (%)	742 (93.7)/50 (6.3)
ALBI grade, 1/2/3, n (%)	323 (40.8)/458 (57.8)/11 (1.4)
Tumor size, cm, mean ± SD/median (IQR)	8.6 ± 4.1/8.2 (5.2-11.5)
Tumor number, mean ± SD/median (IQR)	2.4 ± 2.2/1 (1-3)
AFP, ≤ 400/> 400 ng/mL/NA, n (%)	431 (54.4)/337 (42.6)/24 (3.0)
White blood cell, 109/L, mean ± SD	5.8 ± 2.6
Red blood cell, 106/L, mean ± SD	4.4 ± 0.7
Platelets, 109/L, mean ± SD	158.4 ± 88.9
International normalized ratio, mean ± SD	1.08 ± 0.12
Alanine aminotransferase, U/L, mean ± SD	53.0 ± 47.3
Aspartate aminotransferase, U/L, mean ± SD	67.5 ± 59.6
Albumin, g/L, mean ± SD	38.7 ± 7.0
Total bilirubin, μmol/L, mean ± SD	18.1 ± 8.5
Urea nitrogen, mmol/L, mean ± SD	5.5 ± 3.1
Serum creatinine, μmol/L, mean ± SD	71.9 ± 20.7
Sessions of TACE, mean ± SD/ median (IQR)	2.9 ± 2.0/2 (1-4)

SD: Standard deviation; IQR: Interquartile range; HBV: Hepatitis B virus; ALBI: Albumin-bilirubin; AFP: Alpha-fetoprotein; TACE: Transarterial chemoembolization.

Table 2 Univariate analyses for overall survival

Characteristics	HR (95%CI)	P value
Gender, male (Ref: Female)	0.84 (0.66-1.08)	0.167
Age, per yr increase	1.00 (0.99-1.01)	0.429
Etiology Others (Ref: HBV)	0.79 (0.61-1.04)	0.092
Tumor size, per 1 cm increase	1.10 (1.08-1.13)	< 0.001
Tumor number, per 1 lesion increase	1.11 (1.07-1.15)	< 0.001
Child-Pugh class B (Ref: A)	1.41 (1.00-1.98)	0.047
ALBI grade 2 (Ref: 1)	1.35 (1.14-1.61)	0.001
AFP > 400 ng/mL (Ref: ≤ 400 ng/mL)	1.51 (1.26-1.81)	< 0.001
White blood cell, per 1 109/L increase	1.07 (1.04-1.10)	< 0.001
Red blood cell, per 1 106/L increase	0.87 (0.74-1.03)	0.098
Platelets, per 1 109/L increase	1.00 (1.00-1.00)	< 0.001
International normalized ratio, per 1% increase	0.96 (0.46-1.99)	0.903
Alanine aminotransferase, per 1 U/L increase	1.00 (1.00-1.00)	0.606
Aspartate aminotransferase, per 1 U/L increase	1.00 (1.00-1.01)	0.011
Total bilirubin, per 1 μmol/L increase	1.02 (1.01-1.03)	0.004
Albumin, per 1 g/L increase	0.99 (0.98-1.01)	0.200
ALBI score, per 1 score increase	1.18 (0.99-1.40)	0.062
Blood urea nitrogen, per 1 mmol/L increase	0.98 (0.94-1.02)	< 0.315
Creatinine, per 1 μmol/L increase	1.01 (1.00-1.01)	0.881

HR: Hazard ratio; Ref: Reference; HBV: Hepatitis B virus; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin.

Table 3 Multivariate analyses for overall survival

Characteristics	Model 1		Model 2		Model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Tumor size, per 1 cm increase	1.10 (1.08-1.12)	< 0.001	1.10 (1.08-1.12)	< 0.001	1.10 (1.07-1.12)	< 0.001
Tumor number, per 1 lesion increase	1.10 (1.07-1.14)	< 0.001	1.10 (1.06-1.64)	< 0.001	1.11 (1.07-1.15)	< 0.001
AFP > 400 ng/mL (Ref: ≤ 400 ng/mL)	1.31 (1.09-1.98)	0.047	1.36 (1.13-1.63)	0.001	1.28 (1.06-1.53)	0.010
Child-Pugh class B (Ref: A)
ALBI grade 2 (Ref: 1)			1.44 (1.20-1.72)	< 0.001
Total bilirubin, per 1 μmol/L increase					1.01 (1.00-1.02)	0.025

Significant characteristics (P < 0.05) in univariate analysis were included in cox regression models, and these variables related to liver function (Child-Pugh grade, ALBI grade and total bilirubin) were respectively included in the multivariate Model 1, Model 2 and Model 3. HR: Hazard ratio; Ref: Reference; AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin.

Table 4 Comparison of the performance and discriminating abilities of the proposed models and six-and-twelve criteria

Prognostic models	AUROC (95%CI)			LR χ2	df	C-index (95%CI)	R2
	1-yr	2-yr	3-yr
Model 1	0.72 (0.68-0.76)	0.69 (0.65-0.74)	0.66 (0.60-0.71)	98.4	3	0.65 (0.63-0.68)	0.117
LP = TS + TN + 2.9 × AFP
Model 2	0.72 (0.68-0.76)	0.69 (0.56-0.73)	0.67 (0.61-0.72)	101.4	4	0.66 (0.64-0.69)	0.120
LP = TS + TN + 3.2 × AFP + 3.8 × ALBI
Model 3	0.74 (0.71-0.78)	0.72 (0.68-0.76)	0.68 (0.63-0.74)	124.3	4	0.67 (0.65-0.70)	0.149
LP = TS + 1.1 × TN + 2.7 × AFP + 0.1 × TBIL
Six-and-twelve criteria	0.74 (0.70-0.77)	0.71 (0.67-0.75)	0.68 (0.63-0.74)	114.3	2	0.67 (0.64-0.69)	0.134
LP = TS + TN

AUROC: Area under receiver operating characteristic curve; LR: Likelihood ratio; LP: Linear predictor; TS: Tumor size; TN: Tumor number; ALBI: Albumin-bilirubin grade; AFP: Alpha-fetoprotein; TBIL: Total bilirubin.