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Page 14 of 18 Karademir. Hepatoma Res 2018;4:58 I http://dx.doi.org/10.20517/2394-5079.2018.40

Table 14. The ITA.LI.CA tumor staging system [68]
Diameter of largest tumor (cm) Number of tumors Vascular invasion or metastasis Stage
≤ 2 1 No 0
≤ 3 2-3 No A
2-5 1 No A
3-5 2-3 No B1
> 5 1 No B1
> 5 2-3 No B2
≤ 5 > 3 No B2
> 5 > 3 No B3
Any Any Intrahepatic B3
Any Any Extrahepatic C

Table 15. Development of the ITA.LI.CA integrated prognostic score
Prognostic factor Points
ITA.LI.CA Tumor staging 0 0
A 1
B1 2
B2 3
B3 4
C 5
ITA.LI.CA functional score
Child-Pugh score 5 0
6 1
7 1
8 2
9 2
10-15 3
ECOG PST 0 0
1 1
2 1
3-4 3
AFP (μg/L) ≤ 1,000 0
> 1,000 2
ECOG PST: Eastern Cooperative Oncology Group performance status; AFP: alpha-fetoprotein

Some aspects of the ITA.LI.CA system are rooted in the BCLC staging system. Different than BCLC, ITA.
LI.CA subclassifies BCLC stage B patients into B1, B2, and B3 categories based on degree of intrahepatic tu-
mor burden and presence of intra-extrahepatic metastases. Finally, the serum biomarker AFP was incorpo-
rated as a surrogate for occult vascular invasion, distant metastases, or aggressive tumor biology. Although
the model demonstrated good prognostic discrimination among study patients, it should be noted that there
are significant differences in cancer etiology and treatment choices between European and Asian popula-
tions. Additionally, most patients in both cohorts had good performance status, compensated cirrhosis, and
early or intermediate stage tumors. Whether ITA.LI.CA staging system would perform as well in cohorts
with advanced tumor stage remains to be determined. Furthermore, it needs to be validated in prospective
studies with more contemporary cohorts.

Biomarkers
Early diagnosis and treatment of HCC is crucial for achieving long term survival. Detection of tumor
biomarkers is one of the main methods in reaching this goal. AFP is widely used as serum biomarker
for HCC diagnosis, however, the diagnostic accuracy of HCC with serum AFP exhibits both sensitivity
[69]
and specificity far below satisfaction, especially with small sizes of HCC . With the development of
new technology and advances in research, a number of new and specific biomarkers of HCC have been