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Karademir. Hepatoma Res 2018;4:58 I http://dx.doi.org/10.20517/2394-5079.2018.40 Page 3 of 18

Table 2. Okuda scoring system [6]
Parameters of advance disease
Tumor involving > 50% of the liver
Ascites
Albumin < 3 g/dL
Bilirubin > 3 mg/dL
Stage I No positive parameter
Stage II 1 or 2 positive parameter(s)
Stage III 3 or 4 positive parameters

CURRENTLY AVAILABLE STAGING SYSTEMS FOR HCC
Okuda score
[6]
Okuda staging system was proposed in 1985 based on a study of 850 HCC patients . This system is the first
to combine tumor size (≤ or > 50% of the entire liver) with the variables of liver function such as ascites
(presence and absence), serum albumin (≤ or > 3.0 g/dL) and bilirubin levels (≤ or > 3.0 mg/dL). Based on
these variables, patients are classified into three stages (I: not advanced; II: moderately advanced; III: very
advanced) with different outcomes [Table 2]. Okuda staging system was accepted and widely used as an
improved classification system for HCC. However, at the time of its introduction, most HCC cases were
diagnosed in the advanced stage (18.5% had surgery). It hardly differentiates the less advanced patients.
Therefore, Okuda system is not suitable for the majority of current HCC patients, who are often diagnosed
at an early, asymptomatic stage of the disease with possible indication for today’s therapeutic modalities.
Also, there are major concerns about this system. Considering recent advances in imaging techniques, the
only tumor related variable, tumor size (≤ or > 50% of the entire liver) is defined somewhat arbitrarily. It
does not include vascular invasion, multicentricity or extrahepatic spread of tumor which definitely affect
[14]
patient outcomes . Instead of differentiating early from advance stages, it was found to be useful mainly
to identify end-stage patients (stage III), that should be excluded from therapeutic trials due to their poor
prognosis. When compared with modern staging systems, it has been shown to have lower predictive
capacity [15-19] . Despite these shortcomings, the Okuda staging system has remained a widely accepted and
simple classification system for HCC.

Cancer of the Liver Italian Program score
The Cancer of the Liver Italian Program (CLIP) score was proposed by an Italian group in 1998 based on a
[7]
retrospective analysis of 435 HCC patients treated at 16 Italian institutions . Of these, only 12 (2.8%) had
surgery and 247 (56.8%) underwent locoregional therapy. CLIP was designed to overcome the deficiencies of
the tumor-node-metastasis (TNM) system. It takes into account the Child-Pugh status of the patient with
tumor characteristics including tumor morphology and extension, the portal vein thrombosis and levels
of alfa-fetoprotein (AFP) assign a score (0, 1, 2) to each variable [Table 3]. Patients are classified into seven
groups according to the sum of these scores (0-6). CLIP is easy to calculate, well correlated with survival.
CLIP-0 patient has a better prognosis in comparison to one with CLIP-6 (42.5 mo vs. 1.0 mo of median
survival). However, in this system, information regarding underlying liver diseases, performance status
and extrahepatic metastasis which affect the outcomes were lacking. Additionally, it does not offer any
appropriate therapy for HCC patients.

This scoring system was validated prospectively in 196 HCC patients and showed greater predictive power
[20]
than Okuda staging system . Although, the CLIP score was developed using an appropriate method and
has been externally validated in several (Canadian, Italian and Japanese) cohorts [18-21] ,this score has some
limitations when applied to patients with the early stage of HCC. In countries like Japan, where many
smaller tumors are detected based on the established screening system for HCC, the CLIP score cannot
effectively identify early-stage patients who can benefit from radical treatment.