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Page 6 of 18 Galicia-Moreno et al. Hepatoma Res 2020;6:20 I http://dx.doi.org/10.20517/2394-5079.2019.36

Hepatitis C
HCV infection is another important risk factor for developing HCC. New cases of HCC develop in 3%-5%
[20]
of patients with cirrhosis due to HCV per year . HCV Genotype 1b has been identified as a high risk factor
for HCC development. Studies conducted in Latin America and the Caribbean have reported several other
[21]
risk factors for HCV infection and eventual HCC in specific social minority groups such as drug users ,
[23]
[22]
prison inmates , and sex workers .
Aflatoxin
This is an important risk factor related to HCC development, mainly in Africa and Asia. Aflatoxin is
produced by Aspergillus flavus and is found in maize and peanuts, which causes modifications in the DNA of
[17]
hepatocytes .

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Due to the growing obesity epidemic, nonalcoholic fatty liver disease (NAFLD) is the most common form
of chronic liver disease which includes a clinic-pathologic spectrum of disease ranging from isolated hepatic
steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis or HCC. Once cirrhosis has
developed, NASH pathology may be difficult to evaluate because fatty deposition and inflammation often
disappear. Between 40% to 60% of patients with NASH-induced cirrhosis may develop a complication such
[24]
as HCC after a period of 5 to 7 years. A meta-analysis conducted by Singal et al. , showed an association
between the PNPLA3 variant and an increased risk for HCC, especially in patients with NAFLD-related
cirrhosis. According to the Centers for Disease Control, the incidence of HCC was higher in Latinos than in
[25]
non-Latinos. Latinos with HCC also have shorter survival rates than non-Latinos .
Obesity
This is yet another important risk factor that leads to an increase in the incidence of HCC. In subjects with a
[26]
body mass index of 35 or above, tumor development is more frequent .

In Latin America and the Caribbean, a heterogeneous obesity pattern across the countries has been found.
However, the prevalence of obesity has been increasing, not only among rural populations, the poor and least
[27]
educated, but also the urban populations, the rich and highly educated . Chile and Mexico have the highest
prevalence of overweight and obese boys at 11.9% (9.6-14.3) and 10.5% (8.8-12.4) respectively, while for
[28]
girls, the prevalence in Uruguay and Costa Rica are 18.1% (14.9-21.9) and 12.4% (10.0-15.1) respectively .
In Mexico, mortality data regarding obesity has been calculated and consequently, NAFLD will be the
[29]
second most important cause of liver disease in the future, around 2050 . These data and evidence for the
association between obesity and NAFLD as the third cause of HCC in Latin America, predict an increase
in the incidence of HCC incidence in the near future. Thus, the implementation of measures to incorporate
healthy diets and physical activity in the general population is urgent, in order to achieve healthy body
weights to reduce the incidence of cancer among other chronic diseases such as diabetes mellitus.

Hereditary hemochromatosis
This condition is related with a 200-fold increase in risk for HCC. The formation of free radicals and
[30]
lipoperoxidation products produce iron toxicity in the liver that eventually, can cause cirrhosis and HCC .
Wilson’s disease
This is a heritable disease that is the result of a mutation in the ATP7B gene and causes alterations in plasma
copper circulation. A high content of free copper in circulation induces cytoplasmic cell damage, cirrhosis,
[30]
and eventually HCC .

SCREENING AND DIAGNOSTIC METHODS FOR HCC
The diagnosis of HCC includes screening tests, histopathological and imaging methods. The most widely
used tests for screening are as follows.