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Page 2 of 6 Carvalho et al. Hepatoma Res 2018;4:15 I http://dx.doi.org/10.20517/2394-5079.2018.13

[1]
also the second cause of deaths related to cancer, accounting for 700,000 deaths every year worldwide .

In Brazil, HCC is the 8th most frequent malignant neoplasm and represents approximately 10,000 cases per
[2]
year .
A Brazilian national survey conducted in 2009 showed that hepatic cirrhosis was present in 98% of HCC
patients, and this tumor was more frequent in cirrhosis patients with hepatitis C virus (HCV), hepatitis B
[3]
virus (HBV) chronic hepatitis and alcoholic liver disease .

However, HCC can also be associated with other liver diseases, such as non-alcoholic fatty liver disease
[4]
(NAFLD), nonalcoholic steatohepatitis (NASH), and hemochromatosis as well as toxins .

In patients without cirrhosis, the prevalence of HCC varies between 7% to 54% of the cases and can have a
[5]
major influence on the geographical area . In Western countries, the prevalence of hepatocellular carcinoma
[6-8]
in non-cirrhosis (HCC-NC) patients was estimated in 15% to 20% of cases , and the most common risk
factors were HBV and HCV. However, a majority of the information was obtained from Asia and Africa,
where the prevalence of hepatitis B and C viral infections is also elevated [9-11] .

[12]
NASH is considered a relevant risk factor of liver disease worldwide . Associated metabolic syndrome
[13]
manifestations may also contribute to the development of HCC in patients without cirrhosis .
The present study evaluated the frequency, associated factors and clinical characteristics of HCC in Brazilian
patients without cirrhosis.

METHODS
Design and population study
The present cross-sectional study included patients with HCC diagnosis from two reference centers for liver
disease in Northeast Brazil from 2010 to 2016.

Inclusion criteria were as follows: patients diagnosed with hepatocellular carcinoma of different etiologies
(NAFLD, HBV, HCV, alcohol, hemochromatosis, and etiology related to toxic agents)

Exclusion criteria were as follows: patients diagnosed with hepatocellular carcinoma and cirrhosis.

Diagnostic criteria
The diagnostic criteria for HCC were according to European Association for the Study of the Liver (EASL)
[14]
recommendations .

The criteria for the diagnosis of cirrhosis was histological and/or by the evaluation of non-invasive markers,
9
such as FIB-4 {FIB-4 = age (years) × aspartate aminotransferase (AST) (U/L)/[Platelets (PLT) (10 /L) × alanine
1/2
transaminase (ALT) (U/L)]}.
Clinical assessment
All the data were obtained from a questionnaire containing the following variables: gender, age, and risk
factors for liver diseases (HBV, HCV, NASH, alcohol, and metabolic- and toxic-related factors). The data
from physical examinations and completed additional tests [liver, lipid, and glycemic profiles, serum
insulin, hepatitis B surface antigen (HBsAg), anti-HCV, ferritin, and transferrin saturation index] were
considered. All the patients were also evaluated by at least two imaging methods, such as total abdominal
ultrasonography (US), computed tomography (CT) or magnetic resonance imaging (MRI).