Page 64 - Read Online

stress, bacterial overgrowth, and inflammation. metabolism) produced by Aspergillus flavus and
[24]
Both NAFLD and NASH can further progress to Aspergillus parasiticus, widely represented in nature.
[25]
hepatic fibrosis and eventually to cirrhosis, older The mycotoxin is found in many foods such as corn,
age and deterioration of metabolic status being rice, oil seeds, dried fruits, and peanuts that have
major risk factors for fibrosis progression. NAFLD/ been improperly stored in hot, humid, and unsanitary
[26]
NASH that progresses to cirrhosis carries the highest conditions. Metabolism of aflatoxins by hepatic
[34]
risk for HCC, due to the erratic liver remodeling enzymes may generate reactive epoxide species
with repeated cycles of hepatocellular destruction with the potential of forming a covalent bond with
and compensatory regeneration that characterizes guanine, generating adducts that can promote
[35]
cirrhosis. However, there is increasing concern cellular and macromolecule damage, including
that NAFLD-associated HCC may also occur in non- mutations in the p53 tumor-suppressor gene. [36]
cirrhotic liver, due factors specifically associated Exposure to AFB1 has been associated with HCC in
with NAFLD (e.g. lipotoxicity associated with DNL several cohort studies, supporting a role of AFB1
and increased levels of proinflammatory adipokines/ in liver cancerogenesis-particularly among subjects
cytokines). Recent findings indicate that the who are carriers of hepatitis B surface antigen. [37]
[27]
incidence rate of HCC in NAFLD and NASH is 0.44 and It has been estimated that aflatoxin exposure may
[28]
5.29 cases per 1,000 person-years, respectively. account for 5-28% of total HCC cases worldwide. [38]
Although these rates are lower than those reported
for patients with hepatitis B virus (HBV) or hepatitis Fumonisins are ubiquitous mycotoxins that
C virus (HCV), the number of patients with NAFLD contaminate cereal grains, primarily maize. More
and NASH-related HCC is projected to increase, than 10 compounds have been isolated and
given the increasing prevalence of these conditions. characterized; fumonisin B1 is believed to be the
Epidemiological evidence linking dietary sugar, most toxic among them, as it has been shown to
and specifically, fructose consumption, with cancer be hepatocarcinogenic in rodents. [39-41] Fumonisins
derives from case-control studies that found an are thought to impair the de novo synthesis of
association between high dietary glycemic load and ceramide and sphingolipid metabolism due to a
increased risk for HCC, especially in patients with structural resemblance with ceramide; this may lead
chronic viral hepatitis. [16,17] However, a recent analysis to disruption of signal transduction pathways in
of the European Prospective Investigation into Cancer the target cells. A pathogenic role of exposure to
[42]
and Nutrition (EPIC) cohort revealed an association fumonisins through consumption of moldy corn in
between higher total sugar intake and risk of HCC, human HCC has been suggested by studies carried
but not between glycemic index/glycemic load and out in China. [43-45]
HCC. [18]
Ochratoxin A is another mycotoxin that may have a
Overnutrition [46]
Hepatic cirrhosis and an associated increased risk role in the development of HCC. It may be found in
of developing HCC independent of viral hepatitis cacao and derived products, dried fruits, wine, cereals,
frequently occurs secondary to NASH and NAFLD, [29] green coffee, and spices (mainly nutmeg, paprika,
[47]
which often has a nutritional basis. NAFLD is very coriander, and pepper powder). The carcinogenic
common in obesity and is present in 60-75% of obese effect of ochratoxin A is the result of both direct
persons and 85-95% of morbidly obese persons. genotoxic (covalent DNA adduct formation and
[30]
[48]
Furthermore, it has been proposed that obesity, mutagenicity) and epigenetic mechanisms leading
diabetes, and insulin resistance may predispose to protein synthesis inhibition, oxidative stress and
[49]
to HCC in patients with cirrhosis. [31-33] Thus, in the activation of specific cell signaling pathways. In
the case of HCC arising from NAFLD, it appears a recent case-control study, high performance liquid
that overnutrition is leading to obesity and its chromatography analysis of serum samples from HCC
complications may increase the risk of developing patients and controls indicated that the incidence of
HCC, rather than specific nutrients in the diet. elevated ochratoxin A was highest in the HCC group,
[50]
being 5-fold higher than in the control group.
Food contaminants These findings support a strong association between
Mycotoxins the presence of ochratoxin A and HCC. Ochratoxin
Aflatoxin B1 (AFB1) is a mycotoxin (i.e. toxic A is a stable compound that is not destroyed by
compounds produced by fungal secondary common food preparation procedures.

Hepatoma Research | Volume 2 | March 9, 2016 55