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de Santis et al. Hepatoma Res 2019;5:1 I http://dx.doi.org/10.20517/2394-5079.2018.65 Page 11 of 16

emission tomography (FDG PET), none of the 7 patients with small tumors (< 2 cm in diameter), 18 of 42
patients (43%) with tumors 2-5 cm in diameter, and 32 of 41 patients (78%) with tumors larger than 5 cm
had positive findings for all index lesions. The sensibility increased in Barcelona clinic liver cancer staging
system advanced stage, metastatic HCC and in patients with high levels of alphafetoprotein. All indexed
lesions with positivity in FDG PET correlated with significantly lower survival with respect to patients with
[34]
negative or partially positive PET . As suggested by these results, other trials have demonstrated that PET
positivity correlates with HCC aggressiveness, information which can be used to select, in a non-invasive
[35]
way, candidates for liver transplantation or major liver resection . In a retrospective study conducted on 111
patients with HCC, liver transplantation was performed for 91 of these patients and all underwent PET before
the intervention. The tumor recurrence rate after liver transplantation was 3.6% for patients with non- [18F]
FDG-avid PET tumors, but it was 54.3% for patients with [18F]FDG-avid PET tumors (P < 0.001). The 5-year
recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%)
and patients with PET negative HCC exceeding the Milan criteria (81%) at liver transplantation, but these rates
[36]
were significantly higher than the rate for liver recipients with [18F]FDG-avid advanced HCC (21%, P < 0.002) .

Preoperative evaluation of HCC with FDG PET has shown that well-differentiated and some moderately
differentiated HCCs do not present FDG uptake exceeding that of the surrounding normal liver, whereas
poorly differentiated and undifferentiated HCCs have positive PET findings. The standardized uptake value
(SUV) max of sarcomatous HCC is much higher than that of poorly differentiated HCC. The entity of FDG
captation of both sarcomatous HCC and combined HCC-cholangiocarcinoma is significantly associated
[37]
with tumor differentiation, tumor size, microvascular invasion and with poor prognosis after surgery .

A recently published study conducted on 207 consecutive patients with monofocal HCC undergoing hepatic
resection used pre-operative FDG-PET imaging to stratify tumor aggressiveness and the albumin-bilirubin
(ALBI) grade to stratify the hepatic reserve. The ALBI grade is a simple and objective measurement of liver
function that uses only serum albumin and bilirubin levels and can be applied to all grades of chronic
hepatic diseases, unlike Child Pugh score which is restricted to liver cirrhosis. The study demonstrated a
strong correlation between the values of ALBI, the ratio tumorSUV/non-tumorSUV (TNR) and endpoints
like overall survival and disease-free survival; whereas tumor size and tumor markers were not significant.
Moreover, a high pre-operative TNR showed to be significantly associated with extrahepatic recurrence
[38]
patterns .

The role of PET in the evaluation of tumor response to transarterial treatments has been investigated.
Differently from the good sensitivity shown with cholangiocarcinoma and hepatic metastases of colorectal
cancer treated with transarterial chemoembolization (TACE), PET has shown to be of little diagnostic value
with respect to injected MDCT and MRI for HCC in intermediate stage treated with TACE. Only under
specific circumstances, as in the case of strong PET positivity found in pre-treatment evaluation or the
presence of a large intrahepatic tumor burden treated with yttrium90-radioembolization has PET shown
[39]
accuracy in early evaluation of tumor response .
In conclusion, even if 18F-FDG-PET does not acquire a definite role in guidelines due to its low sensibility
in revealing HCC, it has proved useful in specific instances, such as prior to listing patients with large
HCC for liver transplantation, before major resections or when there is suspicion of an extra-hepatic
neoplastic diffusion. In the last EASL guidelines FDG PET-scan is not recommended for early diagnosis
of HCC because of the high rate of false negative cases but uptake on 18F-FDG-PET seems to be of
potential prognostic value. Therefore, it may facilitate the selection of patients for surgical resection or liver
[28]
transplantation .