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


                              Table 2. HCC in patients without cirrhosis from imaging methods (CT and/or MR)
                              Tumor numbers                       Value, n (%)
                                 1                                 17 (68)
                                 2                                 3 (11.1)
                                 3 or more                         5 (20)
                              Size, median ± SD (cm)               5.1 ± 2.7
                              BCLC, n
                                 0                                 0
                                 A                                 11 (40.7)
                                 B                                 8 (29.6)
                                 C                                 5 (18.5)
                                 D                                 0

                             BCLC: Barcelona Clinic Liver Cancer [16] ; CT: computed tomography; MR: magnetic
                             resonance; SD: standard deviation

               However, this scenario could change over the next few years or decades, since effective treatments for the
               elimination of this virus are currently being used. However, there is a growing increase in NAFLD with
               the prospect of becoming the leading cause of liver disease worldwide associated with risk factors, such as
               dyslipidemia, central obesity, diabetes and metabolic syndrome.


               In the present study, HCV was also the main risk factor for HCC-NC cases, even in areas of Northeast
                                                    [17]
               Brazil, where the prevalence of HCV is low . Perhaps, the prevalence has been influenced by the origin of
               the patients. The patients in the present study were recruited from reference centers for liver disease.

               Chronic HBV infection was also a relevant risk factor for HCC-NC in this patient sample, even after national
               vaccination programs for this virus. These data are extremely concerning. HBV has a direct oncogenic
                    [18]
               effect , and patients without cirrhosis are frequently not included in protocols for the early diagnosis of this
               neoplasm.

               NASH, as the second most frequent risk factor after HCV, in the present series of HCC-NC patients, was
               observed in 14.8% of the cases. Although the prevalence of HCC without cirrhosis in patients with NASH is
               considered low, in some studies [19-21] , NASH also has been recognized as a relevant cause of this liver tumor
               in patients without cirrhosis. In addition, obesity and diabetes, the major risk factors associated with NAFLD
               (steatosis and NASH), are also independent risk factors for HCC [13,22] . In the present study, 33% of the HCC-
               NC patients had diabetes.


               In Brazil, a recent national survey that included 110 cases of HCC associated with NAFLD showed that 31%
                                                                         [23]
               of the cases, diagnosed through liver biopsy, did not present cirrhosis .

               In the present study, a single nodule was observed in 68% of the HCC cases. Treatment with curative intent
               (resection) occurred in 59.3% of the cases. Histopathological evaluation was performed in 81.5% of the cases,
               and 51.9% of the HCC cases were classified as moderately differentiated tumors. This finding is interesting
               since the HCC diagnosis was conducted in patients without cirrhosis, who were not included in protocols for
               early diagnosis and treatment.


               Previous studies have also shown that the majority of HCC-NC cases are diagnosed as a single and larger
               tumor [24,25] , it could be explained because patients with chronic liver disease without cirrhosis are not part of
               the surveillance protocol, and the diagnosis was performed in patients with more advanced stages.


               Although the study presents relevant data, it has some limitations. A lack of knowledge of the prevalence of
               HCC in the reference population is important because the frequency of HCC-NC may be underestimated.
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