Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

Table 1 Demographic and clinicopathological information of 228 enrolled patients, n (%)

Patient characteristic	Pathology		P value
	ICC (n = 99)	LR-M HCC (n =129)
Age, mean ± SD, (range), yr	59 ± 10.2 (57-61)	52 ± 12.8 (50-54)	= 0.017
Sex
Male	51 (51.5)	107 (82.9)	< 0.001
Female	48 (48.5)	22 (17.1)	-
Nodule size, mean ± SD, (range), cm	6.3 ± 2.8 (5.7-6.8)	5.5 ± 3.5 (4.9-6.1)	0.03
Intrahepatic bile duct dilatation	17 (17.2)	3 (2.3)	0.001
CA 19-9 (U/mL)	74.0 (41.9-136.5)	18.8 (16.0-22.0)	< 0.001
AFP (ng/mL)	3.0 (2.7-3.5)	67.3 (18.0-146.7)	< 0.001
Etiology
HBV	20 (20.2)	114 (88.4)	< 0.001
HCV	1 (1)	2 (1.5)	> 0.05
Intrahepatic cholelithiasis	4 (4)	0 (0)	> 0.05
Fatty liver	0	5 (3.9)	> 0.05
Unknown	74 (74.7)	2 (1.5)	< 0.001
Fibrosis stage
S1	3 (3)	4 (3.1)	> 0.05
S2	7 (7.1)	16 (12.4)	> 0.05
S3	4 (4)	20 (15.5)	0.009
S4	2 (2)	60 (46.5)	< 0.001
Unclassified	83 (83.8)	29 (22.5)	-
Tumor tissue differentiation
Well differentiated	1 (1)	2 (1.5)	-
Moderately differentiated	21 (21.2)	59 (45.7)	-
Poorly differentiated	77 (77.8)	68 (52.7)	-

ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; AFP: Alpha fetoprotein; CA 19-9: Carbohydrate antigen 19-9; HBV: Hepatitis B virus; HCV: Hepatitis C virus; SD: standard deviation.

Table 2 Pre-contrast and contrast-enhanced ultrasound features of 228 lesions, n (%)

Imaging characteristic	Pathology		P value
	ICC (n = 99)	LR-M HCC (n = 129)
Gray scale echogenicity
Hyperechoic	4 (4)	39 (30.0)	< 0.001
Hypoechoic	93 (93.9)	82 (63.1)	< 0.001
Mixed	2 (2)	8 (6.9)	> 0.05
APHE
Homogeneous	15 (15.2)	48 (37.2)	< 0.001
Heterogeneous	34 (34.3)	60 (46.5)	> 0.05
Rim	50 (50.5)	21 (16.3)	< 0.001
Early washout (onset < 60 s)	93 (93.4)	124 (96.1)	> 0.05
Marked washout within 120 s	23 (23.2)	10 (7.8)	= 0.002

ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; APHE: Arterial phase hyperenhancement.

Table 3 Comparison of the LR-M features between intrahepatic cholangiocarcinoma and LR-M hepatocellular carcinoma

χ2 test	Rim APHE + late and mild washout		APHE + early and mild washout		APHE + late and marked washout		Rim APHE + early and marked washout		Rim APHE + early and mild washout		Rim APHE + late and marked washout		APHE + early and marked washout
	ICC	LR-M HCC	ICC	LR-M HCC	ICC	LR-M HCC	ICC	LR-M HCC	ICC	LR-M HCC	ICC	LR-M HCC	ICC	LR-M HCC
Positive	4	5	42	101	0	0	14	3	30	13	2	0	7	7
Negative	95	124	57	28	99	129	8	126	9	116	97	129	92	122
Proportion(%)	4	3.9	42.4	78.3	0	0	14.1	2.3	30.3	10.1	2	0	7.1	5.4
P value	> 0.05		< 0.0001		-		0.0018		0.0002		> 0.05		> 0.05
95%CI	-5.6%-6.6%		22.8%-47.8%		-		4.3%-20.4%		9.2%-31.3%		-1.3%-7.1%		-5.2%-9.4%

ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; CEUS: Contrast enhanced ultrasound; LI-RADS: Liver imaging reporting and data system. APHE: Arterial phase hyperenhancement; 95% CI: 95% confidence interval.

Table 4 The receiver operating characteristic curve analysis for diagnostic performance of contrast-enhanced ultrasound liver imaging reporting and data system LR-M characteristics in differentiation intrahepatic cholangiocarcinoma and LR-M hepatocellular carcinoma

Criterion	AUC	95%CI	Sensitivity(%)	95%CI	Specificity (%)	95%CI	+LR	95%CI	-LR	95%CI
Rim APHE	0.7	0.63-0.76	70.4	58.4-80.7	68.8	60.9-75.9	2.3	1.9-2.7	0.4	0.3-0.7
Early washout	0.56	0.49-0.62	57.1	50.3-63.8	54.6	23.4-83.3	1.3	0.7-2.2	0.8	0.4-1.5
Marked washout	0.65	0.59-0.72	69.7	51.3-84.4	61	53.8-67.9	1.8	1.4-2.3	0.5	0.3-0.9
Rim APHE + elevated CA 19-9 + normal AFP	0.82	0.76-0.87	100	86.8-100	63.9	56.8-70.5	2.8	2.5-3.1	-	-

ROC: Receiver operator characteristic curve; AUC: Area under curve; ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; CA 19-9: Carbohydrate antigen 19-9; AFP: Alpha fetoprotein; CEUS: Contrast enhanced ultrasound; LI-RADS: Liver imaging reporting and data system; APHE: Arterial phase hyperenhancement; 95% CI: 95% confidence interval; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio.