Development and validation of a prediction model for microvascular invasion in hepatocellular carcinoma

Table 1 Comparison of participant characteristics in the training and validation cohorts

Characteristic	Training cohort (n = 339)	Validation cohort (n = 115)	P value
Median age (IQR), yr	57 (49, 65)	59 (51, 67)	0.141
Gender
Male	284 (83.8)	104 (90.4)	0.080
Female	55 (16.2)	11 (9.6)
Tumor size, cm	4.5 (3.0, 8.0)	4.0 (2.5, 7.0)	0.095
Number of tumors
Single	285 (84.1)	89 (77.4)	0.104
Multiple	54 (15.9)	26 (22.6)
Child-Pugh grade
A	315 (92.9)	104 (90.4)	0.388
B	24 (7.1)	11 (9.6)
Clinical stage
I	241 (71.1)	80 (69.6)	0.727
II	86 (25.4)	29 (25.2)
III	12 (3.5)	6 (5.2)
Etiology
Hepatitis B	253 (74.6)	93 (80.9)	0.175
Non-hepatitis B	86 (25.4)	22 (19.1)
AFP, ng/mL
≤ 20	142 (41.9)	46 (40.0)	0.122
20–40	81 (23.9)	38 (33.0)
≥ 400 L	116 (34.2)	31 (27.0)
WBC, 109/L
≤ 4.0	83 (24.5)	33 (28.7)	0.371
> 4.0	256 (75.5)	82 (71.3)
Neutrophils, 109/L
≤ 3.0	167 (49.3)	65 (56.5)	0.178
> 3.0	172 (50.7)	50 (43.5)
PLT, 109/L
≤ 125	128 (37.8)	44 (38.3)	0.923
> 125	211 (62.2)	71 (61.7)
RDW
≤ 13.0	119 (35.1)	54 (47.0)	0.024
> 13.0	220 (64.9)	61 (53.0)
NLR
≤ 2.0	150 (44.2)	60 (52.2)	0.141
> 2.0	189 (55.8)	55 (47.8)
PLR
≤ 100	166 (49.0)	65 (56.5)	0.161
> 100	173 (51.0)	50 (43.5)
SII
≤ 300	173 (51.0)	66 (57.4)	0.238
> 300	166 (49.0)	49 (42.6)
PT, sec
≤ 13.0	250 (73.7)	92 (80.0)	0.179
> 13.0	89 (26.3)	23 (20.0)
FIB, g/L
≤ 2.0	90 (26.5)	24 (20.9)	0.225
> 2.0	249 (73.5)	91 (79.1)
ALB, g/L
≤ 40	192 (56.6)	50 (43.5)	0.015
> 40	147 (43.4)	65 (56.5)
ALT, U/L
≤ 40	204 (60.2)	77 (67.0)	0.196
> 40	135 (39.8)	38 (33.0)
AST, U/L
≤ 35	160 (47.2)	62 (53.9)	0.213
> 35	179 (52.8)	53 (46.1)
GGT, U/L
≤ 45	120 (35.4)	38 (33.0)	0.647
> 45	219 (64.6)	77 (67.0)
TB, μmol/L
≤ 19	257 (75.8)	85 (73.9)	0.683
> 19	82 (24.2)	30 (26.1)
ALP, g/L
≤ 120	210 (61.9)	71 (61.7)	0.968
> 120	129 (38.1)	44 (38.3)
GLU, mmol/L
≤ 6.1	278 (82.0)	97 (84.3)	0.567
> 6.1	61 (18.0)	18 (15.7)
ALBI grade
1	164 (48.4)	71 (61.7)	0.017
2	171 (50.4)	41 (35.7)
3	4 (1.2)	3 (2.6)
MVI
Absent	182 (53.7)	63 (54.8)	0.839
Present	157 (46.3)	52 (45.2)
Edmondson-Steiner classification
I–II	142 (41.9)	43 (37.4)	0.396
III–IV	197 (58.1)	72 (62.6)

IQR: Interquartile range; AFP: α-fetoprotein; WBC: White blood cells; PLT: Platelets; RDW: Red blood cell distribution width; NLR: Neutrophil–lymphocyte ratio; PLR: Platelet–lymphocyte ratio; SII: Systemic immune-inflammation index; PT: Prothrombin time; FIB: Fibrinogen; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate transaminase; GGT: γ-glutamyltransferase; TB: Total bilirubin; ALP: Alkaline phosphatase; GLU: Glucose; ALBI: Albumin-bilirubin; MVI: Microvascular invasion.

Table 2 Univariate logistic regression analysis of preoperative data for microvascular invasion presence in the training cohort

Variable	OR (95%CI)	P value
Age, yr	0.981 (0.962–1.001)	0.062
Gender, male vs female	1.488 (0.823–2.689)	0.188
Number of tumors, multiple vs single	5.174 (2.611–10.252)	< 0.001
Tumor size, cm	1.214 (1.155–1.332)	< 0.001
Etiology, non-hepatitis B vs hepatitis	0.837 (0.511–1.370)	0.479
AFP, ng/mL
20–40 vs ≤ 20	1.936 (1.100–3.407)	0.022
≥ 400 vs ≤ 20	4.546 (2.687–7.691)	< 0.001
WBC, 109/L, > 4.0 vs ≤ 4.0	1.117 (0.711–1.927)	0.537
Neutrophils, 109/L, >3.0 vs ≤ 3.0	1.989 (1.289–3.069)	0.002
PLT, 109/L, > 125 vs ≤ 125	1.375 (0.883–2.143)	0.159
RDW, > 13.0 vs ≤ 13.0	1.116 (0.713–1.748)	0.630
NLR, > 2.0 vs ≤ 2.0	1.927 (1.244–2.983)	0.003
PLR, > 100 vs ≤ 100	1.945 (1.261–3.000)	0.003
SII, > 300 vs ≤ 300	2.170 (1.404–3.352)	< 0.001
PT, sec, > 13 vs ≤ 13	1.514 (0.931–2.462)	0.094
ALB, g/L, > 40 vs ≤ 40	0.949 (0.617–1.460)	0.812
ALT, U/L, > 40 vs ≤ 40	0.882 (0.570–1.366)	0.575
AST, U/L, > 35 vs ≤ 35	1.275 (0.831–1.958)	0.266
GGT, U/L, > 45 vs ≤ 45	1.486 (0.947–2.334)	0.085
TB, μmol/L, > 19 vs ≤ 19	1.297 (0.788–2.133)	0.307
ALP, U/L, > 120 vs ≤ 120	1.677 (1.078–2.610)	0.022
FIB, g/L, > 2.0 vs ≤ 2.0	1.397 (0.852–2.290)	0.185
GLU, mmol/L, > 6.1 vs ≤ 6.1	0.904 (0.518–1.579)	0.723
ALBI grade, 1 vs 2 and 3	1.266 (0.825–1.942)	0.281

AFP: α-fetoprotein; WBC: White blood cells; PLT: Platelets; RDW: Red blood cell distribution width; NLR: Neutrophil–lymphocyte ratio; PLR: Platelet–lymphocyte ratio; SII: Systemic immune-inflammation index; PT: Prothrombin time; FIB: Fibrinogen; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate transaminase; GGT: γ-glutamyltransferase; TB: Total bilirubin; ALP: Alkaline phosphatase; GLU: Glucose; ALBI: Albumin-bilirubin; OR: Odds ratio; CI: Confidence interval.

Table 3 Multivariate logistic regression analysis of preoperative data for microvascular invasion presence in the training cohort

Variable	β	OR (95%CI)	P value
Number of tumors, multiple vs single	1.491	4.441 (2.112–9.341)	< 0.001
Tumor size, cm	0.178	1.195 (1.107–1.290)	< 0.001
Neutrophils, 109/L, > 3.0 vs ≤ 3.0	0.539	1.714 (1.036–2.836)	0.036
AFP, ng/mL
20–400 vs ≤ 20	0.670	1.955 (1.055–3.624)	0.033
≥ 400 vs ≤ 20	1.246	3.476 (1.950–6.195)	< 0.001

AFP: α-fetoprotein; OR: Odds ratio; CI: Confidence interval.

Table 4 Accuracy of the nomogram in predicting the risk of microvascular invasion at the optimal threshold value

Variable	Value (95%CI)
	Training cohort	Validation cohort
Sensitivity, %	77.7 (71.1–84.3)	69.2 (56.3–82.2)
Specificity, %	70.9 (64.2–77.5)	68.3 (56.4–80.1)
Positive predictive value, %	69.7 (62.8–76.6)	64.3 (51.3–77.2)
Negative predictive value, %	78.7 (72.3–85.0)	72.9 (61.2–84.6)
Positive likelihood ratio	2.67 (2.10–3.40)	2.18 (1.45–3.27)
Negative likelihood ratio	0.31 (0.23–0.42)	0.45 (0.30–0.69)
Concordance index	0.79 (0.74–0.84)	0.81 (0.74–0.89)
Predicted probability1	0.40	0.40

¹Predicted probability refers to the optimal cut-off value for microvascular invasion prediction based on the maximum Youden index. CI: Confidence interval.