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Page 6 of 9 Giorgio et al. Hepatoma Res 2019;5:20 I http://dx.doi.org/10.20517/2394-5079.2019.05

arterial hyper-enhancement remains the main element for the visualization of the HCC nodule when pure
blood stream contrast agents are used.

This feature was also studied by Giorgio et al. who reported a considerable effectiveness of CEUS in
[40]
detection of arterial hyperenhancement in small nodules (7-20 mm) discovered in cirrhotic patients during
surveillance, so to shorten the diagnostic work-up for the management of HCC.

In Giorgio’s experience, CEUS showed arterial hyperenhancement in 95.5% of HCC nodules, with a
sensitivity of 94.48%, a specificity of 100% and 100% PPV. In this study, CEMRI showed 97% sensitivity, 80%
specificity and 97% PPV. The authors concluded that CEUS has a great capability in detection of arterial
hypervascularity in < 2 cm HCC. In Giorgio et al. ’s experience, only 4.5% of new nodules escaped the
[40]
demonstration of arterial hyervascularity. Therefore authors concluded that “CEUS must be performed
immediately after conventional US to contrast the malignant fate of small lesions arising in a cirrhotic
liver”. Moreover, “CEUS should be included in the diagnostic management of HCC in order to avoid a late
diagnosis, enable an early treatment and improve survival”.

It was shown that CEUS vascular patterns of HCC lesions are related to size and histologic differentiation
of the tumor. Ling et al. reported that < 3 cm HCC nodules show more homogeneous hyperenhancement
[41]
compared to > 3 cm lesions . Moreover, heterogeneous arterial enhancement of HCC nodules > 3 cm were
[41]
followed by faster washout compared to < 3 cm nodules. The portal and late phase washout was faster in
poorly differentiated HCC compared to well-differentiated lesions.

Italian authors also reported that CEUS has high capability in the differential diagnosis of dysplastic nodules
(DN), early hepatocellular carcinoma and progressed HCC . According to this study, DN, early HCC and
[42]
progressed HCC have different and characteristic CEUS patterns. Progressed HCC is characterized by rapid,
intense and homogeneous arterial hyperenhancement, while early HCC displays the so called “reticular
pattern”. This pattern is characterized by inhomogeneous enhancement during arterial phase and complete
enhancement in the late phase. In the experience of the authors, the “reticular pattern” identified early HCC
nodules with a sensitivity of 85.7% and a specificity of 96.1% .
[42]

Comparison among CEUS, enhanced CT and enhanced MRI in diagnosis of small (2-3 cm) HCC
nodules in cirrhosis
Many authors studied the diagnostic capability of CECT, CEMRI and CEUS alone or in combination for the
diagnosis of small HCC on cirrhosis. Aubé et al. carried out a large multicentre study in a large number of
[43]
cirrhotic patients (544 nodules in 381 patients). Authors aimed at evaluating the accuracy of CECT, CEMRI
and CEUS alone and in combination, in diagnosing small (10-30 mm) HCC nodules. The best combination
for the 10-20 mm nodules was CEMRI -CECT. They found that, when a first imaging tool was inconclusive
and CEUS was used as second dynamic technique, this combination allowed the highest specificity with only
a slight drop of sensitivity for 10-20 mm nodules and the highest sensitivity and specificity for 20-30 mm
nodules. The authors concluded that in diagnosis of small HCC nodules the best combination is CEMRI
followed by CEUS .
[43]

Moudgil et al. compared the role of CEUS and CECT in diagnosis of HCC. In their experience, CEUS and
[44]
CECT were similar in demonstrating the arterial hypervascularity of HCC nodules. Vice versa, they found
a better capability of CEUS in the demonstration of washout pattern and the presence of the capsule of the
nodules, when present .

Finally, Intraoperative Contrast-Enhanced Ultrasound (CEUS/IOCEUS) is routinely performed during
surgical resection of HCC in cirrhosis. It has been shown that such technique allows the detection of