Zhang, X. A.,Ryu, S. H.,Xu, Y. J.,Elbaz, T.,Zekri, A. R. N.,Abdelaziz, A. O.,Abdel-Hamid, M.,Thiers, V.,Elena, S. F.,Fan, X. F.,Di Bisceglie, A. M.

Background: Hepatitis C virus (HCV) infection is a well- documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation.