A Novel Nomogram for the Preoperative Prediction of Edmondson-Steiner Grade III-IV in Hepatocellular Carcinoma Patients

Figures & data

Figure 1 Typical pathological section images of Edmondson-Steiner grade. (A) Grade I. (B) Grade II. (C) Grade III. (D) Grade IV.

Table 1 Baseline and Clinicopathological Participant Characteristics According to the Edmondson-Steiner Grade

Variables	E-S Grade I–II (N = 103)	E-S Grade III–IV (N = 137)	P
Age, years^†	57.0 (51.0–67.0)	57.0 (51.0–68.0)	0.417
Sex			1.000
Male	83 (80.6)	110 (80.3)
Female	20 (19.4)	27 (19.7)
BMI, kg/m^2			0.817
≤ 24	60 (58.3)	83 (60.6)
> 24	43 (41.7)	54 (39.4)
HBsAg			0.036
Positive	67 (65.0)	107 (78.1)
Negative	36 (35.0)	30 (21.9)
HCVAb			0.036
Positive	8 (7.8)	2 (1.5)
Negative	95 (92.2)	135 (98.5)
ALBI grade			0.754
1	72 (69.9)	92 (67.2)
2 or 3	31 (30.1)	45 (32.8)
AFP, ng/mL^†	9.4 (3.1–52.5)	79.8 (10.4–425.7)	<0.001
DCP, mAU/mL^†	115.6 (32.6–753.9)	380.6 (73.8–1960.8)	0.031
RDW, %^†	12.9 (12.5–13.4)	12.8 (12.4–13.4)	0.595
NE, ×10^9/L^†	3.0 (2.4–3.8)	3.1 (2.4–3.7)	0.961
LYM, ×10^9/L^†	1.5 (1.2–2.0)	1.4 (1.1–1.8)	0.142
M, ×10^9/L^†	0.4 (0.3–0.5)	0.4 (0.3–0.5)	0.965
PLT, ×10^9/L^†	153.0 (120.0–201.0)	153.0 (107.0–192.0)	0.476
ALT, U/L^†	24.0 (17.5–35.5)	26.1 (19.0–36.4)	0.441
AST, U/L^†	25.9 (20.5–35.0)	27.0 (22.7–35.8)	0.270
GGT, U/L^†	41.9 (28.0–74.0)	44.9 (26.7–76.1)	0.861
TB, μmol/L^†	13.5 (10.2–17.3)	12.9 (9.9–16.6)	0.614
ALB, g/L^†	40.5 (38.7–42.1)	40.3 (38.8–42.2)	0.808
PT, seconds^†	11.3 (10.8–11.8)	11.4 (11.0–12.0)	0.130
INR			0.795
≤ 1	56 (54.4)	71 (51.8)
> 1	47 (45.6)	66 (48.2)
PLR	108.5 (77.6–191.5)	126.7 (86.4–231.4)	0.099
NLR	2.3 (1.7–3.2)	2.4 (1.8–3.4)	0.319
SII	346.2 (228.1–492.7)	378.0 (228.9–546.7)	0.553
ANRI	10.3 (6.3–17.0)	11.8 (8.0–18.3)	0.124
ALRI	21.9 (12.0–39.9)	27.7 (17.5–57.6)	0.029
GLR	27.3 (17.8–55.4)	30.9 (18.9–63.3)	0.357
Number of tumors*			1.000
Solitary	85 (82.5)	112 (81.8)
Multiple	18 (17.5)	25 (18.2)
Tumor diameter, cm*			0.935
≤ 5	64 (62.1)	87 (63.5)
> 5	39 (37.9)	50 (36.5)
Liver cirrhosis*			1.000
Present	42 (40.8)	56 (40.9)
Absent	61 (59.2)	81 (59.1)
Macrovascular invasion*			0.008
Present	8 (7.8)	29 (21.2)
Absent	95 (92.2)	108 (78.8)
MVI			<0.001
Present	15 (14.6)	48 (35.0)
Absent	88 (85.4)	89 (65.0)

Notes: ^†Data are medians, with interquartile range in parentheses. *Imaging results.

Abbreviations: E-S, Edmondson-Steiner; BMI, body mass index; HBsAg, hepatitis B virus surface antigen; HCVAb, hepatitis C virus antibodies; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin; RDW, red blood cell distribution width; NE, neutrophil; LYM, lymphocyte; M, monocyte; PLT, platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl transferase; TB, total bilirubin; ALB, albumin; PT, prothrombin time; INR, international normalized ratio; PLR, platelet to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; SII, systemic immune-inflammation index; ANRI, aspartate aminotransferase to neutrophil ratio index; ALRI, aspartate aminotransferase to lymphocyte ratio index; GLR, γ-glutamyl transferase to lymphocyte ratio; MVI, microvascular invasion.

Table 2 Multivariate Logistic Regression Analysis of Edmondson-Steiner Grade III–IV Based on Univariate Analysis

Variables	β	OR (95% CI)	P
AFP	0.002	1.002 (1.001–1.003)	<0.001
DCP	0.000	1.000 (1.000–1.000)	0.031
HBsAg positive	0.161	1.175 (0.614–2.242)	0.624
HCVAb positive	−2.056	0.128 (0.016–0.667)	0.026
ALRI	0.003	1.003 (0.998–1.009)	0.207
Macrovascular invasion	1.078	2.938 (1.201–7.926)	0.024

Abbreviations: AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin; HBsAg, hepatitis B virus surface antigen; HCVAb, hepatitis C virus antibodies; ALRI, aspartate aminotransferase to lymphocyte ratio index; OR, odds ratio; CI, confidence interval.

Figure 2 Six risk factors associated with Edmondson-Steiner grade III–IV in univariate analysis (p < 0.05). (A) Alpha-fetoprotein (AFP). (B) Des-γ-carboxy prothrombin (DCP). (C) Aspartate aminotransferase to lymphocyte ratio index (ALRI). (D) Hepatitis B virus surface antigen (HBsAg). (E) Hepatitis C virus antibodies (HCVAb). (F) Macrovascular invasion. *p < 0.05, ***p < 0.001. P-values less than 0.05 or 0.001 indicate significant difference.

Figure 3 The development and evaluation of the nomogram model. (A) Established nomogram based on the multivariate logistic regression analysis. (B) The receiver operating characteristic (ROC) curve and area under the curve (AUC) value of the nomogram. (C) The calibration curve of the model (mean absolute error = 0.043).

Figure 4 The decision curve analysis (DCA) (A) and clinical impact curve (B) of the nomogram model.