The present study on the genotypes of 630 hepatitis C infected patients revealed that genotype 4 was confirmed in the majority of these patients (60.8%). This finding confirms previous reports where genotype 4 is a landmark of the infected cases of HCV in Saudi Arabia [
7,
17,
18]. Besides, many review articles that described the global distribution of HCV genotypes [
11,
23,
26,
27], defined clearly that genotype 4 is the dominant genotype in Middle Eastern countries, particularly Saudi Arabia, Egypt, Jordan, Yemen, Oman, and Sudan [
11‐
13,
28]. We also found that genotype 4 was found in higher rate among females than males, but the different was not statistically significant, and this is in line with a similar earlier study in the Kingdom of Saudi Arabia (KSA) [
12].
Future prediction of HCV genotype 1
In Saudi Arabia as in most countries in the region, blood transfusion is quite recent therapeutic measure [
33]. Nowadays, it is mandatory to undertake screening for the two major hepatitis viruses (HCV and HBV) in all donated blood in the country, and this includes testing for HCV (anti-HCV HCV RNA) and HBV (anti-HBc as well as the HBV RNA using molecular techniques) [
16,
20]. Based on our assumption on HCV infection being more common disease among the old generations and with predominance of genotype 4, this status is certainly changing in the near future. There will probably be a tremendous decline in HCV infection rate, particularly the rate of genotype 4 but with dominance of genotype 1, thereby conforming with worldwide distribution of this genotype [
26,
27]. Some studies have shown a clear decline in the incidence of HCV infection in the Saudi Arabia in comparison with previous data from the year 1990, with more decline among children compared to adults [
9,
34]. This was explained by the fact that the perinatal and childhood transmission was not a major mode of transmission as assumed before the last three decades [
34]. Blood transfusion is safer today than previously and is no longer a risk for HCV, HBV, or HIV transmission in the region, particularly after the improvements in the quality of blood supply with especial reliable screening tests and consequent reduction in the risk of transfusion-transmitted infectious diseases [
26,
35,
36]. However, despite the availability of effective measures to ensure the quality and safety of blood and blood products, recently, the WHO has urged regional member states to ensure transfusion safety by promoting safe blood donation, reduce the risk associated with the clinical use, injection safety and infection control in the health care setting, and reducing the resort for unnecessary injections [
37]. Issues concerning the safety of blood during the past 25 years have been associated with changes in blood use and triggered reevaluation of the clinical practices of blood transfusion [
36]. Moreover, the role of health education and the high average income probably allowed more and better access to educational resources in preventive care including physician advice; all together played an important role in the reduction in the transmission of infection [
38].
Although some early studies explored the dominance of HCV genotypes 4 in Saudi Arabia, the majority of these studies did not show the differences in genotypes according to age, Saudis versus non-Saudis, or other ethnicity related factors [
7,
17,
18,
39,
40]. A recent study from KSA, showed increased trend of HCV genotype 1 among those below 50 years old in comparison to genotype 4 in the same age group (46.4% vs. 44.8%) [
12]. Interestingly reports from Bahrain and the United Arab Emirates found genotype 1 to be dominant among the studied population [
10,
41‐
43]. It is known that different genotypes of hepatitis C virus predominate in different regions of the globe. HCV genotypes 1, 2, and 3 can be found across the globe, while genotype 4 is mainly found in the Middle Eastern or African countries [
7,
44,
45]. Confirming this observation, the present study found that 60% of the selected participants had genotype 4 HCV.
The current study has also compared the relationship between HCV genotypes and viral load (viremia level). Viral load refers to the number of virus particles present in the serum or blood. In this study, male patients demonstrated higher rates of viral load than female patients and that viral load was three times more in genotype 1 than genotype 4. Our findings were disagree with those of Al Zayed et al. where viral load levels (IU/ml) were more found with higher reading among patients with genotype 4; however, this could be due to the fact that this sample size was much smaller than our study [
12]. Besides, our findings also disagreement from Indian results which showed that the viral load was higher in genotype 1 indicating that viral clearance of the virus was also delayed. This probably exacerbates the occurrence of higher rates of complications and chronicity of liver disease among their population [
46,
47].
On the other hand the biochemical profiles showed a significant association of AST with genotype 1 and ALT with genotype 4. Clearly, the interaction between the virus and these enzyme in such population infected with HCV genotype 1 in particular needs more clarification and further definitions in large prospective studies.
Although, the rate of co-infections with HBV or HIV in the present study was very low in concordance with the genotypes, our findings demonstrated that patients infected with HCV genotype 4 did not carry any co-infection. This raises the question whether the genotype of HCV is a determinant factor of co-infection with other types of hepatitis viruses and/or with HIV for example? Further studies are needed on the association of other hepatitis viral infections with the specific genotype of HCV.
In Saudi Arabia, blood supply has shifted dramatically from imported blood, to paid donors and, lately, to the current total dependence on the indigenous predominantly voluntary donators with some contribution from donors mainly family members of patients [
9]. However, some studies showed that the rate of blood donation among Saudis was less than satisfactory, probably due to misconceptions, poor knowledge and unfavorable attitudes towards donation [
48‐
52].
As to the possible transmission of some of these transfusion-transmitted infectious diseases some of the patients in the present study, in the mid 1970–1990, must have received blood products mainly in the form of imported blood products which could have been contaminated by some of the viral agents including HCV before the era of the introduction of sensitive screening laboratory tests.
In his recent study on the epidemic dynamics of HCV Al-Qahtani has demonstrated clearly that genotype 4 was transmitted between countries in the region but originated from Egypt. Viral spread between Saudi Arabia and Egypt is predominantly directed towards Saudi Arabia, showing that both HCV genotype 4 epidemics are connected through a source-sink relation, perhaps linked to the large flow of Egyptian migrant workers [
53].
Most of the studies including those by the WHO reported HCV prevalence in Saudi Arabia in the range of 0.4 to 1.1% [
24,
54‐
56], which means that the rate of the infection categorizes the country among those with the lowest prevalence of HCV in the region, according to WHO classification [
57].
This overall reduction in exposure rate may be due to several factors including public awareness of the disease, more and better access to health educational resources such as internet as well as preventive health care. Moreover, the improvement of socio-economic conditions and the level of general education might have also changed the social behavior and cultural habits resulting in reduction in the risks of contamination, in addition to the improvement in donor screening including the use of highly sensitive laboratory assays [
38,
39].
Other measures have been undertaken by the government, such as the barring expatriate who are HCV carrier or chronic HBV carriers when applying for jobs in the KSA. No doubt these steps helped in limiting the sources of infection in the country34. Besides, the successful and effective therapy of chronic hepatitis C patients is now available in the KSA and this step helped in removing the residual sources of new infections. All these steps are expected to play a major contributory role in future in the transformation of the dominant genotype in the country40.
Converted rates of HCV genotypes were demonstrated in our study among the young and young adult generation (< 50 years old). This is probably due to the increased risk of being infected with the HCV genotype 1 among the non-Saudi residents in whom this genotype is dominant in their home countries. A study by Bashawri et al., (2004) found a higher rate of HCV genotype 1 among non-Saudi blood donors than Saudi donors36.
Nowadays, it is crucial to have detailed understanding of the relative HCV genotype prevalence and subtypes in the country and also to develop national treatment strategies including direct acting antiviral therapies. The outcome of such strategies will also facilitate undertaking therapeutic programs that will eventually show a clear cut-off point for the required duration of treatment, cure rates, and the need for interferon and other HCV anti-drugs.
According to our knowledge this is the first study of its types in Saudi Arabia on the correlation between the different HCV genotypes and their contribution to the liver and viral biomarkers.