Quasispecies of genotype 4 of hepatitis C virus genomes in Saudi patients managed with interferon alfa and ribavirin therapy

Abstract

Background and Objectives : Many patients with hepatitis C virus (HCV) infection do not respond to antiviral treatment, possibly due to viral quasispecies. We aimed to investigate whether the quasispeices population could be used as a predictor of response to therapy in our patients. Methods : The quasispecies of HCV genotype 4 (HCV-4) were studied in 25 naïve Saudi patients at zero, three, and six months following interferon alfa and ribavirin combination therapy. Hypervariable region 1 within the E2/NS1 gene of the virus was analyzed by the single-strand conformation polymorphism (SSCP) technique after amplification. Results : Pretreatment DNA bands by SSCP (2-7 bands) were detected in all patients. In those who achieved a complete virological response within six months (viral load < 0.2 Meq/mL; n=7), bands ranged from 2-6 (mean = 3.71±1.25). In six of these seven patients, the number of SSCP bands remained either the same or decreased sequentially. In those patients who did not respond (viral load> 0.2 Meq/mL; n=18), the bands also ranged from 2-7; mean 3.77±1.73. In six of these non-responding patients, the SSCP bands remained the same or decreased sequentially. There was no significant difference between pretreatment quasispecies composition and response (P=.53). Two of the four patients with pretreatment high viral load and the same or decreased composition of quasispecies bands responded to the therapy. Conclusion : Quasispecies in our studied patients cannot be used to predict responsiveness to treatment, but may offer an explanation for failure of most HCV-4 patients to respond to interferon alfa and ribavirin therapy.