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Page 8 of 15 Osho et al. Hepatoma Res 2020;6:55 I http://dx.doi.org/10.20517/2394-5079.2020.42

MRI and immuno-PET/CT. PET MRI has the benefit of improved soft tissue contrast and a lack of ionizing
radiation. However, its availability is limited and requires a technologist experienced in both nuclear
89
[69]
medicine and MRI for accurate interpretation .Immuno-PET/CT uses Zr-tagged monoclonal antibodies
to target glypican-3, a cell surface protein that is highly expressed in HCC, and has shown improvement in
differentiating primary HCC cells from normal hepatocytes and identifying small HCC lesions compared
to PET alone . However, studies evaluating immuno-PET have been limited to animal models, and
[65]
[70]
further studies are needed before its routine use in clinical practice .
Contrast-enhanced ultrasound for HCC diagnosis
There has also been increasing interest in the role of contrast-enhanced ultrasound (CEUS) for HCC
diagnosis. This imaging modality uses the intravenous administration of microbubble contrast agents to
evaluate the hyperenhancement of a liver nodule in “real-time”. These contrast agents have a short half-
life of only a few minutes and are eliminated through respiration, eliminating concerns for potential
[71]
renal toxicity seen with most contrast agents used for CT and MRI . The LI-RADS criteria have been
modified for using CEUS for characterization of liver nodules, similar to the LI-RADS criteria for CT/
MRI . A meta-analysis showed that the pooled sensitivity and specificity of CEUS to detect HCC was 85
[72]
[73]
and 91%, respectively; however, the authors noted the findings were limited by publication bias . There
are several notable limitations of CEUS that are similar to conventional ultrasound in HCC diagnosis.
First, ultrasound is operator-dependent, which may lead to inconsistencies in diagnosis outside of expert
centers . Second, CEUS can also be limited by patient-level factors, including large body habitus,
[74]
overlying bowel gas, poor acoustic windows, and movement artifact [72,74] . A limitation of CEUS in HCC
diagnosis that differs from conventional ultrasound involves the nuances of contrast administration to
properly characterize suspicious lesions. Multiple injections of contrast may be needed to properly classify
lesions, thereby limiting its role for staging, and the administration of contrast must be done in a medically
[74]
[75]
controlled setting to ensure safety . Lastly, CEUS has lower detection rate for washout than CT/MRI ,
and its ability to distinguish HCC from intrahepatic cholangiocarcinoma (ICC) has been controversial [76,77] .
However, some studies have suggested that dynamic, timed administration of contrast can be used in
CEUS to help distinguish the two malignancies, as the rapid loss of signal intensity in the early portal phase
[78]
is more characteristic of ICC than HCC . Additional criteria have been proposed to distinguish ICC and
HCC using CEUS with reported improved performance but require further validation . Based on current
[79]
practice guidelines, CEUS is reserved as a second-line diagnostic imaging modality when multiphase CT or
MRI are indeterminate in HCC diagnosis, although data continue to evolve regarding its potential role .
[7]

ROLE OF IMAGING FOR POST-TREATMENT RESPONSE AND SURVEILLANCE
Patients with early stage HCC are typically eligible for curative therapies including local ablation, surgical
resection, or liver transplantation. Although resection and local ablation are considered curative, they are
associated with a high risk of recurrence, approaching up to 70% at 5 years . Therefore, close observation
[80]
is critical, with most centers performing CT or MRI every 3 months for the first 1-2 years and then semi-
annual surveillance with CT or MRI thereafter. Some centers return to ultrasound-based surveillance
after a period of 4-5 years, although there is substantial center-to-center variation. Liu and colleagues
used clinical and tumor features to risk stratify patients into 3 categories (low, intermediate, and high risk
of recurrence) following surgical resection to determine the optimal time interval for post-hepatectomy
surveillance imaging . They calculated recurrence detection rates between consecutive CT for each
[81]
surveillance schedule for each risk group, and found surveillance schedules could be tailored on the basis
of risk; for example, low-risk patients could undergo surveillance CT every four months for the first two
years and yearly over the next three years without compromising surveillance benefits while reducing
examination costs and radiation burden.