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Page 2 of 11 Paranaguá-Vezozzo et al. Hepatoma Res 2018;4:11 I http://dx.doi.org/10.20517/2394-5079.2018.17

Keywords: Clinical score, hepatocellular carcinoma, hepatitis C

INTRODUCTION
Hepatocellular carcinoma (HCC) represents more than 5% of all malignant tumors, and is the fifth most
common cancer in men and the eighth in women. The prevalence of this cancer is expected to increase
[1-3]
[4-7]
in the coming years . HCC incidence varies greatly between geographical regions . Hepatitis C virus
(HCV) infection is typically prevalent in areas with low incidence (< 3 per 100,000) of HCC, as often found
[6]
in developed countries. Japan is an exception to this, with 80% of HCC patients infected with HCV . It is
generally believed that the presence of cirrhosis and chronic HCV infection contribute to an increased risk
[8]
of HCC . Other potential underlying risk factors include gender (male), advanced age, hepatitis B virus co-
[9]
infection, alcohol abuse, a history of blood transfusion, and diabetes .
Several cohort studies have shown that early HCC detection increases the potential for application of
curative rather than palliative treatment. Screening strategies may allow earlier HCC diagnosis, with a
potential positive impact on mortality [10,11] . The European and American guidelines recommend abdominal
ultrasonography (US) every 6 months [12,13] , but the recently updated Asia-Pacific guidelines, as well as
other centers, recommend a combination of US and serum alpha-fetoprotein (AFP) measurement for HCC
surveillance [14,15] .

[16]
In Brazil, HCV is the main etiology of liver cirrhosis . Among a 10-year cohort of 884 Brazilian cirrhotic
[16]
patients, with almost 60% with HCV etiology, reported an incidence of HCC of 16.9% over 5 years .
Improvements in diagnostic imaging and routine surveillance programs have enabled the identification of
small liver nodules, meaning that the majority of our HCC cases are now diagnosed in their early stages (80%) [17,18] .
As a result, the prognosis for patients with HCC has improved considerably [10,11,19] . However, surveillance
[20]
adherence rates for HCC are far from ideal in many settings . Moreover, HCC rate detection may be lower
outside specialized centers, and the diagnosis of small HCC (≤ 3 cm) can indeed be a challenge in clinical
practice. Therefore, it is important to search for reliable markers for early detection or even exclusion of
HCC with confidence, to assist in the management of these patients.

The aim of this study was to identify possible factors of HCC presence/absence by analyzing a set of patients
with HCV-related cirrhosis, with and without small diameter HCC (≤ 3 cm).

METHODS
We performed an observational case-control study in a cohort of HCV-related cirrhosis patients with and
without small diameter HCC (≤ 3 cm). The STROBE statement for reporting observational studies was
[21]
followed .
HCC patients
The study included 31 patients (20 male, 11 female) with HCV-related cirrhosis and HCC smaller than 3 cm,
who were diagnosed and followed up at a tertiary healthcare center; the Department of Gastroenterology
at the University of São Paulo School of Medicine, São Paulo, Brazil between 1998 and 2003. All patients
on file eligible for inclusion in the HCC group were included. HCC diagnosis was based on one of the three
following criteria: (1) biopsy and histological examination of the nodule; (2) nodules with arterial hyper
vascularization and washout in at least two different dynamic imaging methods [abdominal computed
tomography (CT) or magnetic resonance imaging (MRI)]; or (3) identification of a suspect growth in at least
one dynamic imaging method along with serum AFP > 200 ng/mL.

All biopsies were performed with a 14G Tru-Cut® needle (Medical Technology, Gainsville, FL, USA) with
ultrasound-guided puncture performed in the nodule and in the adjacent parenchyma. HCC was diagnosed