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.

Sequence variation of the HVR1 region of Hepatitis C virus in response to interferon-α and ribavirin treatment

“…sustained virologic response at the end of a follow-up period of 24 weeks [16]. We subsequently showed that quasispeceis evolution during the treatment course does not significantly correlate with response to treatment [18].…”

“…The RNA preparation, cDNA synthesis and PCR amplification were described previously [17]. PCR was performed as described before [18] and numbering of amino acid residues of HVR1 was used as described by Timm et al [19]. The amplification products were cloned into PCR 2.1 TA vector (InVitrogen, San Diego, CA, USA) according to the manufacturer's instructions and were used to transform E. coli INVα F' competent cells (InVitrogen).…”

Interaction Between the Neglected Tropical Disease Human Schistosomiasis and HCV Infection in Egypt: a Puzzling Relationship

“… 123 One possible reason for this is the great diversity of virus quasi species present in each patient, which provides a reservoir of mutations that enable virus-escape from anti-viral therapy. 124 , 125 A very recent study conducted on Egyptian patients clearly demonstrated a significant association between positive serology for schistosomal infection and failure to HCV treatment despite anti-schistosomal therapy with praziquantel. 126 This further supports that bilharzial infection complicates HCV disease progression and treatment.…”

How to optimize HCV therapy in genotype 4 patients

“…The presence of multiple HCV species in the pretreatment serum of HCV4 patients could be a major cause of HCV4 resistance to treatment. Greater sequence heterogeneity generates diverse quasispecies, providing a reservoir of mutations that enable virus‐escape from antiviral therapy .…”