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

ABSTRACT

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. The quasispecies of HCV genotype 4 [HCV-4] were studied in 25 naive 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. 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. 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