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Page 6 of 10 Yapali et al. Hepatoma Res 2018;4:24 I http://dx.doi.org/10.20517/2394-5079.2018.57

genotypes of HCV were described. In the Eastern Mediterranean countries, there are 2 predominant
genotypes; genotype 4 in the Arab countries (except Jordan) and genotype 1 in non-Arab countries (Islamic
Republic of Iran, Israel and Turkey) . Egypt is of particular importance with more than 90% of genotype 4
[58]
HCV infection . The distribution of HCV genotype in Jordan differed from the other Arab countries,
[59]
predominantly genotype 1a (40%), followed by genotype 1b (33%) and genotype 4 (33.3%) . The most
[60]
common genotype in Southern Israel was genotype 1b (62%) while genotype 4 (78%) was predominant in
the Gaza Strip . Turkey serves as a bridge between Europe and Asia, and HCV genotype pattern is similar
[61]
to Eastern and Southern European countries, having genotype 1b as the most frequent genotype (> 70%)
followed by genotype 1a . HCV genotype 3a is the most common subtype in Iran followed by genotype
[62]
1a, 1b and 4 . The predominant genotypes (1a and 4) are the most difficult-to-treat groups. The association
[63]
between the HCV genotype and the risk of HCC is based on the epidemiological data however one can
speculate that the poor response to interferon (IFN)-based regimens in genotype 1 and 4 patients may
explain the disease progression and high risk of HCC development.

Chronic HCV infection leads to HCC following a multistep carcinogenesis pathway. Interferon (IFN)-based
regimens provided sustained virologic response (SVR) in 40%-50% of patients . Recently developed direct-
[64]
acting antivirals (DAAs), which directly target the viral protease, polymerase, or non-structural proteins,
have achieved a revolutionary improvement of SVR rate over 90% .
[65]

In developing countries, less than 10% of HCV-infected patients can access to DAAs. Despite the
high antiviral efficacy, high cost of the medications is a major barrier to the access to treatment of the
sufferers [66,67] . In addition, more than 50% of infected individuals have unrecognized HCV infection .
[68]
These patients generally present with advanced liver disease. Each year approximately 3-4 million newly
infected cases are expected, the burden of HCV-related liver disease will remain to be high, even in the
developed countries.

A systematic review including 13 studies on 2386 patients in Egypt estimated the annual rates of death/
transplantation, decompensation and HCC in patients with compensated HCV cirrhosis to be 4.58%, 6.37%
and 3.36%, respectively . In 2014, an estimated 125,000 viremic individuals/year were diagnosed with HCV
[69]
infection. Of these 10% had chronic hepatitis, 30% had compensated cirrhosis, and the majority (60%) were
diagnosed with decompensated cirrhosis or HCC [70,71] . The high prevalence of HCC in HCV patients was
reported to be associated with decompensated cirrhosis in Egypt .
[72]
In the Eastern Mediterranean countries, treatment strategies are determined by the availability of resources,
availability of medications and expected number of cases. In the countries, which have access to DAAs,
treatment is prioritized for patients with advanced fibrosis and cirrhosis. In 2014, national committee for
control of viral hepatitis (NCCVH) in Egypt negotiated with the industry to decrease the price of DAAs.
Furthermore, local generic treatments were encouraged and decreased the cost of treatment. This program
provided treatment of large number Egyptian genotype 4 HCV patients. This model needs to be reproduced
in other developing countries to decrease the risk of cirrhosis and HCC in HCV-infected individuals.
Elimination of HCV by 2030 is one of the major targets of WHO by implementing models to reduce the
rate of new infections and provide treatment access in middle and low income countries. Many countries
including Australia, Brazil, Egypt, Georgia, Germany, Iceland, Japan, the Netherlands and Qatar are on the
track to eradicate hepatitis C by 2030.

Hepatitis D virus
The hepatitis D virus (HDV) is an incomplete RNA virus, which is dependent on HBsAg for transmission
and replication [73,74] . HDV leads to fulminant hepatitis and further disease progression among hepatitis
B infected patients. The long-term co-infection of HBV and HDV presents a worse prognosis than CHB