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Yapali et al. Hepatoma Res 2018;4:24 I http://dx.doi.org/10.20517/2394-5079.2018.57 Page 5 of 10

respectively . But the lack of high quality data and data registry systems represent a major challenge to
[42]
determine the epidemiology of HCC in this region. Universal HBV vaccination is the most effective strategy
to reduce the incidence of HCC. A 20-year follow-up report from Taiwan - an endemic region - clearly
showed that HCC incidence among subjects 6-19 years of age decreased in the vaccinated cohort (64 HCC
in 37,709,304 person-years), compared to the non-vaccinated cohort (444 HCC in 76,496,406 person-years),
with the adjusted relative risk (RR) of 0.31 .
[43]
The impact of vaccination programs on the incidence of HCC development in the Eastern Mediterranean
countries needs to be clarified in future studies. However, many challenges remain. The war in this region
leads to low or decreased coverage of vaccination programs. Furthermore, immigration after war is a major
threat for the application of immunization programs, identification and treatment of CHB patients that will
change the epidemiological trends for HBV and HBV-related HCC in the Eastern Mediterranean countries.

Chronic hepatitis C
HCV is one of the major global causes of liver-related death and morbidity. The risk of HCC is increased 15-20
fold in patients chronically infected with HCV infection. Over the last decade, HCV seroprevalence is estimated
to increase by 2.8%, accounting for more than 185 million infections worldwide . A systematic review analyzing
[44]
the studies published between 2000 and 2015 from 138 countries (representing the 90% of the global population)
estimated global HCV prevalence at 2.5%. Central Asia and Central Africa are estimated to have the highest
prevalence (> 3.5%); East, South and Southeast Asia, West and East Africa, North Africa and Middle East,
Southern and Tropical Latin America, Caribbean, Australasia, and Eastern Europe moderate prevalence (1.5%-
3.5%); while Southern Africa, North America, Andean and Central Latin America, Pacific Asia and Western and
Central Europe have low prevalence (< 1.5%). The global viremic rate was 67%, with HCV varying from 48.7% in
Central Asia to 80.2% in Tropical Latin America . HCV genotype 1 is the most frequent genotype followed by
[45]
genotype 3 (17.9%), genotype 4 (16.8%), genotype 2 (11%), genotype 5 (2%) and genotype 6 (1.4%) . The genotypes
[45]
reported to be associated with high risk of HCC are genotype 1b and genotype 3 [46-48] .

Chronic HCV infection causes increased inflammation and cell-turnover leading to cirrhosis and
development of dysplastic nodules and HCC . Unlike HBV, HCV-associated hepatocarcinogenesis is
[39]
more likely to be related to the indirect effects of the virus on the host cellular processes such as increased
hepatocyte proliferation and steatosis, virus-induced inflammation and oxidative stress inducing genomic
mutations and genome instability, mitochondrial damage and induction of reactive oxyen species, and virus-
induced host immune responses . In untreated patients, cirrhosis develops in 14%-45% of patients 20 years
[19]
after transmission of HCV . In patients with HCV-related cirrhosis, annual rate of HCC is 1%-4%, therefore
[49]
patients with advanced fibrosis and cirrhosis should undergo HCC surveillance. The risk factors for HCC are
older age, black race, HCV genotype 1b, co-infection with HBV or HIV, diabetes, obesity, steatosis, heavy
alcohol consumption and low platelet levels in patients with cirrhosis [49-52] .

The HCV prevalence in the Eastern Mediterranean region ranges from 1% to 2.5% in most countries, with higher
prevalence reported in Egypt (> 10%), and in Libyan Arab Jamahiriya, Sudan and Yemen (2.5%-10%) . In the
[53]
Eastern Mediterranean region of WHO, it is estimated that at least 23 million people have HCV infection .
[53]
This represents almost the total of HCV patients in Europe and US. Regarding the parenteral spread by the
previous use of intravenous anti-schistosomal treatment campaigns, HCV prevalence is very high in Egypt,
particularly in the age group of 40-60 years [54-56] . A high prevalence of HCV among children born after these
campaigns is explained by unsafe injections [54-56] . In Pakistan, the prevalence of HCV is variable from 2% to
14%, and HCV transmission in this region is due to unsafe injections .
[57]

HCV genotype is an important epidemiological determinant for the source and the possible mode of
transmission. Furthermore, genotype has a substantial role in predicting the treatment response. Six major