Clinical value of contrast-enhanced ultrasound in early diagnosis of hepatocellular carcinoma

Table 1 Patient characteristics at baseline, n (%)/mean ± SD

Characteristic	Value or case
Male	83 (66.40)
Age (years)	56.74 ± 11.25
BMI (kg/m2)	23.58 ± 3.45
History of hepatitis B	63 (50.40)
Alcoholic liver disease	19 (15.20)
Family history of liver cancer	28 (22.40)
ALT (U/L)	48.73 ± 21.16
AST (U/L)	44.82 ± 19.87
ALB (g/L)	38.42 ± 4.37
TBIL (μmol/L)	22.48 ± 6.89
AFP (ng/mL)	392.35 ± 106.33
Single lesion	91 (72.80)
Maximum diameter of lesion (cm)	3.74 ± 1.85
Clear boundary	88 (70.40)
Hypoechoic lesions	72 (57.60)

BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALB: Albumin; TBIL: Total bilirubin; AFP: Alpha-fetoprotein.

Table 2 Pathological typing

Project	n (%)
Conventional type HCC	89 (71.20)
Clear cell HCC	24 (19.20)
Fibrolamellar HCC	12 (9.60)
Grade I (highly differentiated)	18 (14.40)
Grade II (moderate differentiation)	64 (51.20)
Grade III-IV (low differentiation)	43 (34.40)
Ki-67 > 20%	47 (37.60)
CK19 positive	29 (23.20)
AFP positive	98 (78.40)
Glypican-3 positive	113 (90.40)
MVI positive	42 (33.60)
Capsule invasion	31 (24.80)

HCC: Hepatocellular carcinoma; Ki-67: Antigen Kiel 67; CK19: Cytokeratin 19; AFP: Alpha-fetoprotein; MVI: Microvascular invasion.

Table 3 Contrast mode

Project	n (%)
Fast-in and fast-out	45 (36)
Fast-in and slow-out	50 (40)
Continuous enhancement	30 (24)

Table 4 Arterial phase enhancement time

Project	n (%)
APT < 15 seconds	50 (40)
APT ≥ 15 seconds	75 (60)

APT: Arterial phase enhancement time.

Table 5 Washout initiation time and washout completion time

Project	n (%)
WIT < 60 seconds	55 (44)
WIT ≥ 60 seconds	70 (56)
WCT < 180 seconds	60 (48)
WCT ≥ 180 seconds	65 (52)

WIT: Washout initiation time; WCT: Washout completion time.

Table 6 Longest diameter and enhanced area

Project	n (%)
LD ≤ 3 cm	50 (40)
LD > 3 cm	75 (60)
EA ≤ 10 cm2	52 (41.60)
EA > 10 cm2	73 (58.40)

LD: Longest diameter; EA: Enhanced area.

Table 7 Boundary characteristics of lesions

Boundary characteristics category	n (%)
Clear boundary	49 (39.20)
Fuzzy boundary	42 (33.60)
Annular enhancement at the edge	34 (27.20)

Table 8 Correlation analysis results

Indicator	Degree of differentiation	APT	WIT	WCT	LD	EA
Degree of differentiation	1
APT	-0.427b	1
WIT	-0.238a	0.593b	1
WCT	-0.443b	0.628b	0.679b	1
LD	-0.468b	0.614b	0.442a	0.602b	1
EA	-0.215a	0.472b	0.406a	0.535b	0.601b	1

^aP < 0.05.

^bP < 0.01.

APT: Arterial phase enhancement time; WIT: Washout initiation time; WCT: Washout completion time; LD: Longest diameter; EA: Enhanced area.

Table 9 Results of logistic regression analysis

Factor	β	SE	Wald χ2	P value	OR	95%CI
PEI	1.215	0.531	5.412	0.020a	3.374	1.23-9.19
WIT	-0.615	0.312	4.024	0.045a	0.541	0.298-0.974
Boundary characteristics of lesions	0.943	0.483	3.82	0.051	2.564	0.996-6.604
APT	-0.752	0.318	5.625	0.018a	0.471	0.244-0.911

^aP < 0.05.

SE: Standard error; OR: Odds ratio; CI: Confidence interval; PEI: Peak enhancement intensity; WIT: Washout initiation time; APT: Arterial phase enhancement time.

Table 10 Receiver operating characteristic curve analysis results

Indicator	Cutoff value	Sensitivity (%)	Specificity (%)	AUC	95%CI	Youden’s index
PEI	1.45	85.2	72.5	0.893	0.840-0.946	0.577
WIT	12.3	78.9	67.3	0.851	0.796-0.906	0.463
Boundary characteristics of lesions	0.98	80.5	69.1	0.876	0.822-0.930	0.495
APT	10.5	82.4	74.1	0.864	0.810-0.918	0.564

AUC: Area under the curve; CI: Confidence interval; PEI: Peak enhancement intensity; WIT: Washout initiation time; APT: Arterial phase enhancement time.

Table 11 Subgroup analysis situation

Indicator	CEUS sensitivity (%)	CEUS specificity (%)	CT/MRI sensitivity (%)	CT/MRI specificity (%)	P value
Overall	89.7	85.2	91.1	88.3	> 0.05
LI-RADS 5	82.4	92.1	87.3	94.6	0.032a

^aP < 0.05.

CEUS: Contrast-enhanced ultrasound; CT: Computed tomography; MRI: Magnetic resonance imaging; LI-RADS: Liver Imaging Reporting and Data System.