Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study

Figures & data

Figure 1 Flowchart showing the patient selection process, construction, and external validation of the nomogram.

Table 1 Baseline Characteristics of BCLC Stage 0/A HCC Patients Who Underwent Hepatectomy in the Training and External Validation Cohorts

Variables		Training Cohort (n=500)	External Validation Cohort (n=308)
Gender
	Male	428 (85.6%)	267 (86.7%)
	Female	72 (14.4%)	41 (13.3%)
Age (years)
	<60	344 (68.8%)	201 (65.3%)
	≥60	156 (31.2%)	107 (34.7%)
HBV DNA (IU/mL)
	<10,000	356 (71.2%)	216 (70.1%)
	≥10,000	144 (28.8%)	92 (29.9%)
HBsAg
	Negative	87 (17.4%)	51 (16.6%)
	Positive	413 (82.6%)	257 (83.4%)
AFP (ng/mL)
	<400	353 (70.6%)	214 (69.5%)
	≥400	147 (29.4%)	94 (30.5%)
TBIL (µmol/L)		12.80 (9.60–16.50)	14.15 (10.60–17.80)
ALB (g/L)		40.90 (38.30–43.78)	42.85 (40.20–44.98)
Lymphocyte (×10^9/L)		1.55 (1.22–1.88)	1.44 (1.15–1.86)
Hemoglobin (g/L)		143.00 (133.00–153.00)	144.00 (132.25–153.00)
Platelet (×10^9/L)		153.50 (119.00–197.00)	134.00 (102.25–179.00)
ALBI grade
	1	349 (69.8%)	248 (80.5%)
	2	151 (30.2%)	60 (19.5%)
	3	0 (0%)	0 (0%)
HALP score
	>38.20	413 (82.6%)	262 (85.1%)
	≤38.20	87 (17.4%)	46 (14.9%)
Tumor size (cm)		3.80 (2.50–5.60)	4.10 (2.80–6.70)
Number of tumors
	Solitary	480 (96.0%)	298 (96.8%)
	Multiple	20 (4.0%)	10 (3.2%)
BCLC stage
	0	62 (12.4%)	27 (8.8%)
	A	438 (87.6%)	281 (91.2%)
CSPH
	Negative	428 (85.6%)	250 (81.2%)
	Positive	72 (14.4%)	58 (18.8%)
Surgical approach
	OLR	222 (44.4%)	189 (61.4%)
	MILR	278 (55.6%)	119 (38.6%)
Resection method
	NAR	335 (67.0%)	186 (60.4%)
	AR	165 (33.0%)	122 (39.6%)
EBL (mL)
	<200	205 (41.0%)	113 (36.7%)
	≥200	295 (59.0%)	195 (63.3%)
OT (min)
	<180	204 (40.8%)	111 (36.0%)
	≥180	296 (59.2%)	197 (64.0%)
Blood transfusion
	No	459 (91.8%)	290 (94.2%)
	Yes	41 (8.2%)	18 (5.8%)
Cirrhosis
	No	113 (22.6%)	132 (42.9%)
	Yes	387 (77.4%)	176 (57.1%)
E-S grade
	I–II	282 (56.4%)	184 (59.7%)
	III–IV	218 (43.6%)	124 (40.3%)
Satellite nodules
	Negative	449 (89.8%)	281 (91.2%)
	Positive	51 (10.2%)	27 (8.8%)
MVI
	Negative	391 (78.2%)	241 (78.2%)
	Positive	109 (21.8%)	67 (21.8%)

Abbreviations: HBV DNA, hepatitis B virus DNA; HBsAg, hepatitis B surface antigen; AFP, alpha-fetoprotein; TBIL, total bilirubin; ALB, albumin; ALBI, albumin-bilirubin grade; HALP, hemoglobin, albumin, lymphocyte, and platelet score; BCLC, Barcelona Clinic of Liver Cancer; CSPH, clinically significant portal hypertension; OLR, open liver resection; MILR, minimally invasive liver resection; NAR, non-anatomical anatomical resection; AR, anatomical resection; EBL, estimated blood loss; OT, operation time; E-S, Edmondson-Steiner grade; MVI, microvascular invasion.

Table 2 Univariate and Multivariate Cox Regression Analysis of Independent Risk Factors Associated with Disease-Free Survival (DFS) in the Training Cohort

Variables	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P value	HR (95% CI)	P value
Gender
Male	Reference
Female	0.689 (0.461–1.029)	0.069
Age (years)
<60	Reference
≥60	1.125 (0.857–1.476)	0.397
HBV DNA (IU/mL)
<10,000	Reference		Reference
≥10,000	1.857 (1.425–2.420)	< 0.001	1.820 (1.357–2.440)	< 0.001
HBsAg
Negative	Reference		Reference
Positive	1.655 (1.134–2.415)	0.009	1.492 (0.997–2.231)	0.051
AFP (ng/mL)
<400	Reference		Reference
≥400	1.691 (1.292–2.213)	< 0.001	1.296 (0.969–1.734)	0.080
ALBI grade
1	Reference		Reference
2	1.529 (1.171–1.997)	0.002	1.087 (0.817–1.446)	0.565
HALP score
>38.20	Reference		Reference
≤38.20	2.151 (1.594–2.903)	< 0.001	1.963 (1.414–2.726)	< 0.001
Tumor size (cm)	1.139 (1.092–1.188)	< 0.001	1.080 (1.026–1.138)	0.003
Number of tumors
Solitary	Reference
Multiple	1.695 (0.987–2.909)	0.056
BCLC stage
0	Reference		Reference
A	2.375 (1.429–3.947)	0.001	1.407 (0.818–2.417)	0.217
CSPH
Negative	Reference		Reference
Positive	1.677 (1.215–2.316)	0.002	1.793 (1.274–2.524)	0.001
Surgical approach
OLR	Reference
MILR	1.052 (0.812–1.363)	0.701
Resection method
NAR	Reference
AR	0.960 (0.729–1.265)	0.774
EBL (mL)
<200	Reference
≥200	1.203 (0.924–1.568)	0.170
OT (min)
<180	Reference
≥180	1.202 (0.923–1.565)	0.173
Blood transfusion
No	Reference
Yes	1.013 (0.634–1.620)	0.956
Cirrhosis
No	Reference
Yes	1.372 (0.983–1.916)	0.063
E-S grade
I–II	Reference		Reference
III–IV	1.623 (1.255–2.097)	< 0.001	1.457 (1.110–1.914)	0.007
Satellite nodules
Negative	Reference		Reference
Positive	2.458 (1.741–3.470)	< 0.001	1.935 (1.349–2.777)	< 0.001
MVI
Negative	Reference		Reference
Positive	2.272 (1.716–3.006)	< 0.001	1.642 (1.209–2.229)	0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; HBV DNA, hepatitis B virus DNA; HBsAg, hepatitis B surface antigen; AFP, alpha-fetoprotein; TBIL, total bilirubin; ALB, albumin; ALBI, albumin-bilirubin grade; HALP, hemoglobin, albumin, lymphocyte and platelet score; BCLC, Barcelona Clinic of Liver Cancer; CSPH, clinically significant portal hypertension; OLR, open liver resection; MILR, minimally invasive liver resection; NAR, non-anatomical anatomical resection; AR, anatomical resection; EBL, estimated blood loss; OT, operation time; E-S, Edmondson-Steiner grade; MVI, microvascular invasion.

Figure 2 (A) The nomogram model for predicting 2-year and 5-year DFS. (B) The 2-year and 5-year receiver operating characteristic (ROC) curve of DFS in the training cohort. (C) The 2-year and 5-year ROC curves of DFS in the external validation cohort.

Figure 3 Calibration curve for predicting the 2-year DFS (A) and the 5-year DFS (B) in the training cohort and the 2-year DFS (C) and the 5-year DFS (D) in the external validation cohort.

Figure 4 DCA plots for the nomogram in predicting the 2-year DFS (A) and the 5-year DFS (B) in the training cohort and the 2-year DFS (C) and the 5-year DFS (D) in the external validation cohort.

Figure 5 The Kaplan-Meier survival curves for low-, intermediate- and high-risk groups of BCLC stage 0/A HCC patients after radical liver resection based on our nomogram calculated risk scores. The disease-free survival Kaplan-Meier survival curves in the training cohort (A) and the external validation cohort (B). The overall survival Kaplan-Meier survival curves in the training cohort (C) and the external validation cohort (D).

Data Sharing Statement

The datasets used and analyzed in this study can be obtained from the corresponding author upon reasonable request.