**2.3.3 Aflatoxin**

A connection between the environmental exposure to aflatoxin, a mycotoxin produced by *Aspergillus* fungus, and primary liver cancer has also been documented. The chronic dietary exposure to high levels of this toxin is seen predominantly in developing countries, where hepatitis B is also prevalent. It has been postulated that the overall contribution of aflatoxin exposure to hepatocellular carcinoma cases worldwide is between 5 and 28% (Y. Liu 2010). However, taking into account that hepatitis B infection seems to play a much greater role in the risk of development of hepatoma in these developing countries, the true contribution of aflatoxins is considered minimal. It appears that the mechanism by which this toxin has carcinogenic effects is by causing mutations in the p53 tumor suppressor gene (Gursoy-Yuzugullu, 2011).

### **2.3.4 Nonalcoholic fatty liver disease**

Nonalcoholic fatty liver disease is the most common form of chronic liver disease in developed countries. When aggressive, this disease can progress to cirrhosis and hepatocellular carcinoma. The alarming obesity epidemic affecting many of these nations, and components of the metabolic syndrome in particular insulin resistance and diabetes, are factors associated with the development of this chronic disease. These factors by themselves have also been related to an increased risk of primary liver cancer (Calle, 2003; El-Serag, 2004). Considering our current understanding of its rising prevalence, nonalcoholic fatty liver disease could also be responsible for a significant number of the idiopathic or cryptogenic cirrhosis cases as well as the cryptogenic cirrhosis-related hepatoma cases that are seen in industrialized countries (Bungianesi, 2002). Recent studies have shed some light of the molecular mechanisms by which fatty liver and obesity could eventually lead to hepatic cancer (Beyazit, 2010; Park et al., 2010; Wree, 2011).
