Contrast-enhanced ultrasound Liver Imaging Reporting and Data System: Lights and shadows in hepatocellular carcinoma and cholangiocellular carcinoma diagnosis

Table 1 Characteristics of patients and hepatic nodules

Item	Number or range
Nodules, n	511
Patients, n	269
Males, n (%)	219 (81.4)
Females, n (%)	50 (18.6)
Median age at first nodule (IQR; range)	69 years (61-75; 43-88)
Males (IQR; range)	67 years (59-74; 43-88)
Females (IQR; range)	74.5 years (71-78; 59-85)
Hepatic cirrhosis aetiology (n)
Chronic HCV infection, n (%)	129 (48)
Alcohol abuse, n (%)	45 (16.7)
Chronic HBV infection, n (%)	24 (8.9)
Chronic HCV infection + alcohol abuse, n (%)	21 (7.8)
Chronic HBV + HCV infection, n (%)	8 (3)
NASH, n (%)	6 (2.2)
ChronicHBV infection + alcohol abuse, n (%)	5 (1.9)
Other aetiologies, n (%)	6 (2.2)
Unknown aetiology, n (%)	25 (9.3)
Median diameter of nodules (IQR; range)	24 mm (16-36; 5-200)

IQR: Inter quartile range; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Non-alcoholic steatohepatitis.

Table 2 Rates of different conclusive diagnoses for each Contrast-enhanced ultrasound Liver Imaging Reporting and Data System class

		Conclusive diagnosis						%
		HCC	ICC	Metastasis	Other malignancy	Benign lesion	Total
CEUS LI-RADS class	CEUS LR-M	11	21	3	1	1	37	7.2
	CEUS LR-5	286	0	0	0	2	288	56.4
	CEUS LR-4	111	0	0	0	3	114	22.3
	CEUS LR-3	15	2	0	2	47	66	12.9
	CEUS LR-2	0	0	0	0	5	5	1.0
	CEUS LR-1	0	0	0	0	1	1	0.2
	Total	423	23	3	3	59	511	100.0
%		82.8	4.5	0.6	0.6	11.5	100.0

CEUS LI-RADS: Contrast-enhanced ultrasound Liver Imaging Reporting and Data System; HCC: Hepatocellular carcinoma; ICC: Intrahepatic cholangiocarcinoma.

Table 3 Rates of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in different Contrast-enhanced ultrasound Liver Imaging Reporting and Data System classes

CEUS LI-RADS class	HCC	ICC
LR-3	15/66 (22.7%)	2/66 (3%)
LR-4	111/114 (97.4%)	0/114 (0%)
LR-5	286/288 (99.3%)	0/288 (0%)
LR-M	11/37 (29.7%)	21/37 (56.8%)

CEUS LI-RADS: Contrast-enhanced ultrasound Liver Imaging Reporting and Data System; HCC: Hepatocellular carcinoma; ICC: Intrahepatic cholangiocarcinoma.

Table 4 Rates of different contrast-enhanced ultrasound patterns in arterial phase

Arterial phase CEUS pattern	Nodules, n (%)
Homogeneous hyperenhancement	404 (79.1)
Rim hyperenhancement	23 (4.5)
Globular hyperenhancement	1 (0.2)
Isoenhancement	65 (12.7)
Hypoenhancement	18 (3.5)

CEUS: Contrast-enhanced ultrasound.

Table 5 Rate of different portal and late phase contrast-enhanced ultrasound patterns

Portal and late phase CEUS pattern	Nodules, n (%)
Late and mild washout	310 (60.7%)
Early/marked washout	27 (5.3%)
Isoenhancement	157 (30.7%)
Hypoenhancement	15 (2.9%)
Hyperenhancement	2 (0.4%)

CEUS: Contrast-enhanced ultrasound.

Table 6 Diagnostic statistics of different contrast-enhanced ultrasound Liver Imaging Reporting and Data System classes for different diagnosis

Tested association	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Diagnostic accuracy (%)	Youden’s index	Odds Ratio	P value
CEUS LR M-ICC	91.3 (72.0-98.9)	96.7 (94.7-98.1)	56.8 (39.5-72.9)	99.6 (98.5-99.9)	96.5 (94.5-97.9)	0.880	309.75	< 0.001
CEUS LR 5-HCC	67.6 (62.9-72.1)	97.7 (92.0-99.7)	99.3 (97.5-99.9)	38.6 (32.1-45.3)	72.8 (68.7-76.6)	0.653	89.80	< 0.001
CEUS LR 4-HCC	26.2 (22.1-30.7)	96.6 (90.4-99.3)	97.4 (92.5-99.5)	21.4 (17.5-25.8)	38.4 (34.1-42.7)	0.228	10.10	< 0.001
CEUS LR 4/5-HCC	93.9 (91.1-95.9)	94.3 (87.2-98.1)	98.8 (97.1-99.6)	76.1 (67.0-83.8)	93.9 (91.5-95.8)	0.882	253.50	< 0.001
CEUS LR 3-benign lesion	79.7 (67.2-89.0)	95.8 (93.5-97.5)	71.2 (58.7-81.7)	97.3 (95.3-98.6)	93.9 (91.5-95.8)	0.755	89.26	< 0.001
CEUS LR-3-malignancy	4.2 (2.5-6.5)	20.3 (11.0-32.8)	28.8 (18.3-41.3)	2.7 (1.4-4.7)	6.0 (4.2-8.5)	-0.755	0.01	< 0.001
CEUS LR-3-iso-iso-malignancy	5.3 (0.1-26.0)	19.1 (9.1-33.3)	2.6 (0.1-13.5)	33.3 (16.5-54.0)	15.2 (7.5-26.1)	-0.756	0.01	< 0.001
CEUS LR-3-hypo-hypo-malignancy	57.9 (33.5-79.7)	91.5 (79.6-97.6)	73.3 (44.9-92.2)	84.3 (71.4-93.0)	81.8 (70.4-90.2)	0.494	14.78	< 0.001

CEUS: Contrast-enhanced ultrasound; HCC: Hepatocellular carcinoma; ICC: Intrahepatic cholangiocarcinoma; PPV: Positive predictive value; NPV: Negative predictive value.

Table 7 Classification of nodules for LR-3, LR-4, and LR-5 classes, reported in yellow, orange, and red, respectively

Nodule size	No APHE1		APHE1		Total
	< 20 mm	≥ 20 mm	< 10 mm	≥ 10 mm
No washout of any type	37 (4)	21 (5)	1 (1)	106 (104)	165
Late and mild washout	7 (5)	8 (7)	0	288 (286)	303
Total	44	29	1	394	468

¹With the exclusion of nodules with rim and peripheral discontinuous globular arterial phase hyper-enhancement belonging to contrast-enhanced ultrasound LR-M and contrast-enhanced ultrasound LR-1 classes, respectively.

Number of hepatocellular carcinomas in brackets. APHE: Arterial phase hyperenhancement.