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Karademir. Hepatoma Res 2018;4:58 I http://dx.doi.org/10.20517/2394-5079.2018.40 Page 15 of 18

discovered. Besides AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3) and DCP have been incorporated
in current staging systems as factors reflecting tumor progression (BALAD and bm-JIS). Although some
[70]
reports have not been consistent about the significance of both AFP-L3 and DCP in the diagnosis of HCC ,
they are considered as promising biomarkers especially for the diagnosis of small HCC with low level of
[71]
AFP . To improve their diagnostic sensitivity and specificity, combined tests of AFP, AFP-L3 and DCP are
[72]
often applied in clinical practice .
Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes neovascularization
and endothelial cell proliferation, significantly increases in serum of HCC patients compared with control
individuals and correlates with venous invasion, advanced tumor stage and poor prognosis [73,74] . Furthermore,
[75]
the expression of VEGF in HCC tissues was related to invasiveness and metastasis of HCC . However,
[76]
VEGF may also be increased in other cancers and its value for early diagnosis of HCC is also unclear .
Additionally, other biomarkers such as Golgi glycoprotein 73, a transmembrane Golgi glycoprotein, and
Glypican 3, a cell-surface heparan proteoglycan have been studied and found to be promising biomarkers
[71]
which have high sensitivity and specificity for the diagnosis of small HCC with negative AFP . With the
development of genomics and proteomics, more and more new biomarkers will be discovered and used in
clinical settings to diagnose different stages of HCC.

CONCLUSION
Over the past 20 years, diagnostic tools and treatment modalities have improved and screening programs
have led to earlier diagnosis of HCC. Liver transplantation, hepatic resection, RFA, and transarterial
chemoembolization have all been used in these patients to achieve a curative therapy. However, according
to the degree of hepatic functional loss and heterogeneous nature of the tumor, optimal management for
these patients remains controversial. Therefore, there is an increasing need for a staging system that can
reflect the prognosis and permit the better stratification of these patients for clinical trials. To date, several
staging systems have been proposed with various combinations of clinical, biochemical and pathological
factors. However, search for a comprehensive staging system with appropriate treatment options applicable
worldwide to all HCC patients despite geographical, financial and etiologic differences continues.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.