Hepatitis C genotype 4: Genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia

Abstract

Background/Aim:Hepatitis C virus genotypes 4 (HCV-4) is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze (i) the variability of the HCV-4 subtypes, the route and source of HCV transmission and (ii) the influence of HCV-4 subtypes on their therapeutic response.Patients and Methods:Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon (PEG-IFN) α-2a and ribavirin therapy.Results:Positive history of blood or blood products transfusion was noted in 22 patients (34%), hemodialysis in 10 patients (15.6%), surgery in 7 patients (11%), and unknown etiology in 25 patients (39%). Prevalence of HCV-4 subtypes was 4a = 48.4% (31/64), 4d = 39% (25/64), 4n = 6.25% (4/64), and remaining combined (4m, 4l, 4r, 4o) 6.25% (4/64). No significant correlation between subtypes and the source of transmission was recognized (P = 0.62). Sustained virological response in all HCV-4 patients was 64% (41/64), while in each subtypes separately it was 4a 77.4% (24/31), 4d 52% (13/25), and combined (4n, 4m, 4l, 4r, 4o) 62.5% (5/8) (P = 0.046).Conclusion:No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype.

Meta-analysis

“…Two studies did not contain original data[52, 98]. Three studies did not evaluate treatment-naïve patients[31, 32, 97], one study did not have at least 25 HCV-4 patients[33], and three studies included patients co-infected with hepatitis B virus, HIV, or other liver diseases[44, 70, 82]. After conducting a comprehensive review, a total of 44 articles and 7 abstracts met eligibility criteria and were included in the meta-analysis (Figure 1).…”

The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia

“…The absence of subtype 4d in surveillance studies in West Africa383940 and Central Africa9414243 suggests that this subtype may have emerged along a more eastward trajectory. Although subtype-level data from this region are scarce, the detection of HCV4d in 22% of seropositive samples in a small-scale Ethiopian survey44 supports such a scenario, as do the likely introduction of this subtype in southern Italy by returning colonists, of whom 82% were stationed in the Horn of Africa (Eritrea, Ethiopia and Somalia, the others inhabited Libya)45, and its high prevalence in Saudi Arabia1213.…”

“…This variant is rarely reported (<1%) in the well-surveyed Egyptian epidemic13, but the large population of migrant workers from the Horn of Africa3031 may have facilitated HCV4d dispersion in a similar way as for HCV4a from Egypt. Therefore, whereas the Saudi Arabian samples dominate the subtype 4d dataset, the reconstructed HCV4d demographic history (Fig.…”

“…Virus spread between Saudi Arabia and Egypt is predominantly directed towards Saudi Arabia, showing that both HCV4a epidemics are connected through a source-sink relation, perhaps linked to the large flow of Egyptian migrant workers13. The virus is also transmitted from Egypt to countries from geographically diverse locations that were grouped in the ‘other’ category (Table 1).…”

“…the presence of other subtypes in a region (e.g. subtypes 4n, 4m, 4l, 4r and 4o in Saudi Arabia13 and 4f, 4l, 4m, 4n and 4o in Egypt60) indicates that among all variants introduced, HCV4d was the one that by chance was able to benefit most from changes in human behaviour in Saudi Arabia, as was the case for HCV4a in Egypt. The remarkable difference in absolute scale of the HCV epidemics in both regions, with prevalences of respectively ~1.5% in Saudi Arabia versus ~15% in Egypt1, is likely explained by the PAT campaigns that amplified the Egyptian subtype 4a1011 but not the subtype 4d reservoir.…”