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Vezeridis et al. Hepatoma Res 2020;6:53 I http://dx.doi.org/10.20517/2394-5079.2020.36 Page 7 of 10

that having CEUS available at the time of surveillance ultrasound reduces time to diagnosis, healthcare
expenditures, and patient anxiety [12,40] .

Similar to CT/MRI LI-RADS®, CEUS LI-RADS® should only be applied in populations at risk for HCC by
AASLD guidelines, including patients with cirrhosis of any etiology or noncirrhotic patients with chronic
hepatitis B.

DIFFERENCES BETWEEN CEUS LI-RADS AND CT/MRI LI-RADS
As the reader may be more acquainted with CT/MRI LI-RADS®, we will highlight some differences between
CEUS LI-RADS® and CT/MRI LI-RADS® to reinforce the utility and some unique aspects of CEUS.

CEUS practitioners have long used the term “nodule” to describe possible lesions of interest, so in CEUS
LI-RADS® “nodule” is often used interchangeably with the term “observation”. In CT/MRI LI-RADS®, the
term “observation” is favored as APHE on CT/MRI may be due to arterioportal shunting or other pseudo-
lesions. By contrast, CEUS does not show these AP shunts and is a very important tool to differentiate
[10]
them from HCC without washout . Conversely, a suspected arterioportal shunt on CT/MRI associated
[41]
with a distinct nodule on US will raise suspicion for HCC .

CEUS and CT/MRI exhibit differences in enhancement and washout due to differences in the contrast
agents employed for each. CEUS agents are several microns in diameter, which confines them to be purely
intravascular contrast agents. CT/MRI contrast agents are much smaller in size and therefore have an
extracellular interstitial phase of contrast. As a result of these differences, a “capsule” appearance is typically
seen in HCC when assessed by CT/MRI and is therefore a major criterion for categorization as LR-5 by
CT/MRI LI-RADS®. Capsule appearance is not seen by CEUS and is therefore not one of the major features
[10]
used for categorization by CEUS LI-RADS® .
DISCUSSION
Structured reporting systems such as BI-RADS® and LI-RADS® emerged due to the need for increased
[18]
consistency of imaging diagnostics . These systems typically are created based on existing data and
expertise, but the validation of real-world use is critical. An international multi-center prospective clinical
trial has been organized by members of the CEUS LI-RADS® working group to assess the diagnostic
accuracy of CEUS for HCC diagnosis in patients at risk for HCC, assess the interreader reliability of
[42]
diagnosis, and to validate CEUS LI-RADS® . Recruitment is still ongoing as of the time of writing.
There are existing retrospective data to support the use of CEUS LI-RADS® and provide the prevalence
of HCC within each of the categories from a large international case series out of Europe and Canada.
[43]
Terzi et al. showed that in 848 patients with 1006 lesions of median size 2 cm, the specificity of LR-5 for
HCC diagnosis was 98.5%. Concern has been raised historically that CEUS may misdiagnose ICC, however,
this was not found to be of concern in this large case series. None of the 519 LR-5 nodules were pure
ICC, although one nodule was found to represent mixed HCC-ICC. Regarding the LR-M category (8% of
lesions), 38% were ICC, 10% were mixed HCC-ICC, 48% were HCC, and 2% were metastases. A large study
of 2020 patients with hepatitis B virus (HBV) infection from China validated CEUS LI-RADS® for patient
populations in whom HBV is endemic - with LR-5 showing high specificity of 96% and positive predictive
[44]
value of 98% for the diagnosis of HCC . More recently, similar diagnostic accuracy was observed in
another large retrospective study of patients from China who were predominantly (92%) HBV positive -
[45]
with LR-5 showing a sensitivity and specificity of 73% and 97%, respectively for nodules 20 mm or less .
Retrospective data regarding the interreader reliability of CEUS LI-RADS® is encouraging. The largest