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Vezeridis et al. Hepatoma Res 2020;6:53 I http://dx.doi.org/10.20517/2394-5079.2020.36 Page 3 of 10
[18]
and data collection for diagnosis of HCC in patients at risk of HCC, initially for CT and MRI in 2011 .
Recognizing the value and worldwide utilization of CEUS to diagnose HCC, ACR convened a Working
Group of international experts in CEUS to develop CEUS LI-RADS® starting in April 2014. The first official
[19]
version of CEUS LI-RADS® (version 2016) was published online in September 2016 .
Similar to CT/MRI LI-RADS®, CEUS LI-RADS® is updated at regular intervals. As of the time of writing, the
Working Group is finalizing the CEUS LI-RADS® v2019 manual. The most updated versions of LI-RADS®,
including CEUS LI-RADS® version 2017, can be found on the ACR website (https://www.acr.org/Clinical-
Resources/Reporting-and-Data-Systems/LI-RADS/).

CEUS is recognized as one of the imaging modalities for HCC diagnosis by many societies worldwide
[2]
including European Association for the Study of the Liver (EASL) , the Asian Pacific Association for
[21]
[20]
the Study of the Liver (APASL) , Japanese Society of Hepatology , Korean Liver Cancer Study Group-
[23]
[22]
National Cancer Center , Canadian Association for the Study of the Liver (CASL) , Italian Association
[24]
for the Study of the Liver (AISF) , and the World Federation for Ultrasound in Medicine and Biology-
[17]
European Federation of Society for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) .
Historically it was removed in the prior American Association for the Study of Liver Diseases (AASLD)
[26]
[25]
guidelines and EASL 2012 guidelines due to the concern of misdiagnosis of ICC as HCC based on a
[27]
small retrospective study . The authors reviewed 21 ICC cases retrospectively and reported 10/21 (47.6%)
of ICC showed homogeneous hyperenhancement followed by a washout on CEUS, therefore they could
have been misdiagnosed as HCC. However, subsequent experience and publications do not support the
[2]
interpretation of this small retrospective study [28-30] . While current EASL guidelines now endorse CEUS ,
[3]
AASLD has not included CEUS in its new guidelines . More data and experience in the United States may
help recognition of CEUS for HCC diagnosis in the United States.
MAJOR FEATURES OF CEUS LI-RADS®
The characteristic appearance of HCC by CEUS is due to the purely intravascular nature of the microbubble
contrast agent as well as the biology of HCC, which is a vascular tumor that derives its blood supply from
the hepatic artery (and not the portal vein). As a result, HCC has a typical CEUS appearance of arterial
phase hyperenhancement (APHE) and relative hypoenhancement (washout) in the portal venous or late
phase compared to the surrounding liver . The washout of HCC is most commonly late (defined as > 60 s)
[9]
and mild. As a result of these observations regarding the appearance of HCC by CEUS, the “major features”
that are used to define HCC by CEUS LI-RADS® are arterial phase hyperenhancement and late and mild
[19]
washout .
DESCRIPTION OF THE CEUS LI-RADS ALGORITHM
The algorithm of CEUS LI-RADS® integrates the major features of HCC by CEUS (enhancement and
washout) as well as size to stratify the likelihood of HCC by imaging appearance . The stratification is
[19]
performed according to the same Likert scale of CT/MRI LI-RADS®, from LI-RADS 1 (LR-1) meaning
definitely benign to LI-RADS 5 (LR-5) meaning definitely HCC [Table 1]. Figure 1 is the CEUS LI-RADS®
algorithm and its diagnostic table for LR-3 to LR-5.

If one or more major features cannot be assessed due to image omission or degradation, the nodule/
observation should be designated as LR-NC (non-categorizble).

Tumor in a vein (LR-TIV) is categorized when the classic arterial hyperenhancement and late mild washout
of HCC are seen in soft tissue mass within a vein. A review and subsequent meta-analysis of the diagnostic
accuracy of CEUS for diagnosis of a tumor in vein support high sensitivity and specificity from several