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Puoti. Hepatoma Res 2018;4:57 I http://dx.doi.org/10.20517/2394-5079.2018.67 Page 7 of 11

[47]
effective treatments . Several studies have shown that elderly patients with HCC have a worse prognosis
compared to non-elderly ones, but such difference is not due to higher age, but rather seems to be the
[48]
consequence of undertreatment . In elderly patients undergoing treatment, survival was unaffected by
[49]
age .
From a clinical point of view, staging systems in HCC should define outcome prediction and treatment
assignment. Due to the nature of HCC, the main prognostic variables are tumor stage, liver function and
[8]
performance status .

[3]
The most accepted clinical classification of HCC has been proposed by the Barcelona Clinic Liver Cancer .
The BCLC staging system has come to be widely accepted in clinical practice and is also being used for
many clinical trials of new drugs to treat HCC. Therefore, it has become the de facto staging system that is
[8]
used, and it was first endorsed by the EASL , and thereafter by the AASLD guidelines for the management
[3]
of HCC .
This clinical classification does stratify patients with HCC into 5 different stages (stage 0 and stages A to D),
according to the ECOG Performance Status (PST) and the Child Pugh Classification. Each stage is further
subdivided according to four pre-established prognostic clinical and biochemical parameters (size of the
nodule, number of nodules, portal pressure, bilirubin levels).

Beyond its clinical utility, the BCLC staging allows to allocate stage-specific treatment strategies and predicts
expected survival.

In summary: (1) The main established parameters for the definition of the stage of HCC are: 1) tumor sta-
tus; 2) number and size of nodules; 3) presence/absence of macrovascular invasion; 4) presence/absence of
extraheaptic spread; 5) liver function; 6) Child-Pugh class; 7) serum bilirubin; 8) albumin levels; 9) presence/
absence of portal hypertension; 10) physical status; 11) ECOG classification; and 12) presence of symptoms;
(2) prognosis prediction is defined by variables related to tumor status (size, number, vascular invasion, N1,
M1), liver function (Child-Pugh’s) and health status (Eastern Cooperative Oncology Group, ECOG); and (3)
treatment allocation incorporates treatment dependant variables, which have been shown to influence thera-
peutic outcome, such as bilirubin, portal hypertension or presence of symptoms-ECOG.

The 5-stage classification [1,4-6] categorizes patients into very early HCC (stage 0), early HCC (stage A),
intermediate HCC (stage B), advanced HCC (stage C) and end-stage HCC (stage D).

Stage 0 - patients in the BCLC stage 0 are well-preserved liver function, belonging to the Child Pugh class
A and with a performance status 0. In this “very early” status there is a single nodule with size < 2 cm (or
carcinoma in situ) without vascular invasion/satellites; portal pressure and bilirubin may be normal or
increased. In the first case, patients are suitable for curative treatment as resection; on the contrary, if portal
pressure and/or bilirubin levels are increased or extra-hepatic associated disease are present, resection might
be contraindicated, and patients should undergo other curative treatments, such as liver transplantation, or
local ablation with percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA).

Stage A - patients in the BCLC stage A (early stage) show the following features: (1) single HCC nodule > 2
cm but < 5 cm, or three nodules < 3 cm; (2) ECOG 0; (3) Child Pugh Class A or B; and (4) absence/presence
of associated extra-hepatic diseases.

In the absence of associated diseases, the patients might be candidates to liver transplantation; otherwise,
local ablation with PEI or RFA should be considered. Single tumors beyond 5 cm are still considered for