Sonazoid-contrast-enhanced ultrasound for the histological diagnosis of hepatocellular carcinoma

Table 1 Comparison of Kupffer phase contrast-enhanced ultrasonography parameters between well-differentiated and poorly differentiated hepatocellular carcinoma lesions and identification of independent predictors of tumor differentiation, n (%)/mean ± SD

Variable	Univariate analysis			Multivariate analysis
	Well-differentiation (n = 137)	Poor differentiation (n = 102)	P value	OR	95%CI	P value
Clinicopathologic features
Males	126 (92.0)	86 (84.3)	0.064
Age, year	56 ± 11	54 ± 12	0.138
HBsAg-positive	113 (82.5)	87 (85.3)	0.447
AFP ≥ 7 ng/mL	67 (48.9)	81 (79.4)	0.000	2.799	1.334-5.871	0.006
Ki-67 expression level	73 (53.3)	83 (81.4)	0.000
Vascular invasion	34 (24.8)	48 (47.1)	0.001
US features
Tumor size (cm)	4.3 ± 2.5	5.4 ± 2.9	0.003	1.055	0.931-1.196	0.397
Cirrhosis	84 (59.2)	58 (40.8)	0.488
AP (hyper, iso, hypo-enhancement)	134, 3, 0	98, 3, 1	0.474
PVP (hyper, iso, hypo-enhancement)	10, 84.43	6, 69, 27	0.599
DP (hyper, iso, hypo-enhancement)	1, 16, 120	0, 11, 91	0.669
KP (hyper, iso, hypo-enhancement)	1, 2, 134	0, 2, 100	0.660
CEUS
Arterial phase
OT (second)	15.0 ± 3.0	15.2 ± 3.8	0.660
PT (second)	24.9 ± 5.4	24.7 ± 6.6	0.835
RT (second)	9.9 ± 3.6	9.5 ± 4.3	0.424
PIAV (second)	34.2 ± 5.8	33.0 ± 6.7	0.151
Kupffer phase
EIAV (dB)	52.4 ± 5.3	54.1 ± 5.3	0.015	0.945	0.869-1.027	0.183
ID (dB)	6.9 ± 4.3	12.2 ± 4.8	0.000	1.048	0.862-1.273	0.636
IR	1.127 ± 0.114	1.299 ± 0.137	0.000	110887.3081	121-101163217	0.001

¹The binary Logit regression analysis (Supplementary material).

HBsAg: Hepatitis B surface antigen; AFP: Alpha-fetoprotein; US: Ultrasonography; AP: Arterial phase; PVP: Portal venous phase; KP: Kupffer phase; OT: Onset time; PT: Peak time; RT: Rise time; PIAV: Peak intensity absolute value; EIAV: Enhancement intensity; ID: Intensity difference; IR: Intensity ratio; DP: Delayed phase; CEUS: Contrast-enhanced ultrasound.

Table 2 Diagnostic performance of variables

Variable	Cut-off value	Sensitivity (%)	Specificity (%)	AUC
AFP (ng/mL)	97.69	57.4	83.6	0.739
Tumor size (cm)	4.65	53.9	70.8	0.610
EIAV (dB)	56.384	40.2	78.1	0.590
ID (dB)	9.184	80.4	74.5	0.815
IR	1.215	82.4	86.9	0.877

AUC: Area under the receiver operating characteristic curve; AFP: Alpha-fetoprotein; EIAV: Enhancement intensity; ID: Intensity difference; IR: Intensity ratio.