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Yapali et al. Hepatoma Res 2018;4:24 I http://dx.doi.org/10.20517/2394-5079.2018.57 Page 3 of 10

Table 2. Etiology of HCC in Eastern Mediterranean countries
Location Alcohol HBV HCV Other
Afghanistan 11% 36% 32% 21%
Bahrain 17% 39% 28% 16%
Cyprus 32% 19% 39% 14%
Dijibouti 13% 33% 36% 18%
Egypt 12% 13% 63% 12%
Iran 6% 44% 24% 26%
Iraq 12% 37% 32% 19%
Israel 15% 20% 49% 17%
Jordan 15% 35% 31% 19%
Kuwait 15% 37% 31% 18%
Lebanon 17% 28% 40% 15%
Libya 15% 33% 34% 18%
Morocco 14% 31% 36% 19%
Oman 17% 39% 28% 16%
Pakistan 7% 16% 54% 23%
Qatar 18% 38% 28% 15%
Saudi Arabia 17% 41% 17% 25%
Somalia 15% 36% 30% 18%
Sudan 18% 35% 30% 16%
Syria 14% 32% 34% 19%
Tunisia 18% 20% 44% 18%
Turkey 19% 26% 44% 11%
United Arab Emirates 21% 44% 22% 13%
Yemen 8% 44% 35% 12%
[8]
Adapted from reference . HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus

RISK FACTORS FOR HCC
The major risk factors for HCC are the presence of cirrhosis, and HBV/HCV infection. Other factors, such as
aflatoxin B exposure and nonalcoholic steatohepatitis (NASH) are important in certain regions of the world.
In the high-incidence countries of Asia and Africa, chronic HBV infection and aflatoxin B exposure are the
major risk factors. Exceptionally, in Japan and Egypt the most common risk factor is HCV infection. On
the contrary, excessive alcohol consumption and metabolic syndrome play more important roles in the low-
incidence regions. In addition, inherited metabolic disorders such as hemochromatosis, A1AT deficiency,
tyrosinemia, several porphyrias also increase the risk of HCC .
[13]

The distribution of viral and other risk factors of HCC in the Eastern Mediterranean countries are
summarized in Table 2.

Chronic hepatitis B
Countries with HBV prevalence of greater than 2% have increased incidence and mortality rates of HCC.
The majority (70%-90%) of HBV-related HCC develops in patients with cirrhosis [14,15] . In persons chronically
infected with HBV, the risk of HCC has been shown to increase up to 30-fold [14,15] . As a result of hepatic
inflammation and liver damage, genetic and epigenetic defects lead to development of HCC [16-18] . However, in
the absence of cirrhosis HCC can develop in 10%-20% of HBV-infected individuals as a result of integration
of HBV into the host genome that induces chromosomal alterations and insertional mutagenesis of cancer
genes [17-19] . The genetic instability of the hepatocyte triggers the clonal growth of hepatocytes before the
liver damage occurs. HBV-encoded X protein (HBx) which is a multifunctional protein that regulates the
expression of genes in the involved in the signal cascades, has a pivotal role in the pathogenesis of HBV-
related HCC [17-19] . In addition to cirrhosis, other factors reported to increase HCC risk among patients with
chronic HBV comprise; demographic (male sex, older age, Asian or African ancestry, family history of HCC),
viral [higher levels of HBV replication, HBeAg positivity, HBV genotype, longer duration of infection, co-