HEPATITIS-C VIRAL COMPLEXITY DETECTED BY SINGLE-STRAND CONFORMATION POLYMORPHISM AND RESPONSE TO INTERFERON THERAPY

Background/Aims: Hepatitis C virus (HCV) genome heterogeneity by sequence analysis in association with interferon (IFN) inefficacy has been reported. This study was performed to establish a convenient method for detecting the HCV quasispecies complexity and to determine the correlation between the complexity and the responsiveness to IFN therapy in patients with chronic hepatitis C. Methods: The quasispecies complexity of HCV hypervariable region 1 in patients treated with IFN-alpha was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). Results: Seven of 25 patients (28%) with low complexity (SSCP band number of less than or equal to 2) were HCV RNA negative after treatment, whereas in 24 patients with high complexity (SSCP band number of greater than or equal to 3), the response to IFN was almost insignificant because only 1 patient (4.5%) remained HCV RNA negative after treatment (P < 0.05). Among type 1b patients, IFN therapy was only effective for patients with low amounts of HCV RNA (less than or equal to 10(7.5) copies/mL serum) and low complexity. In contrast, most type 2a patients tended to respond to the therapy with exceptions being those with high amounts of HCV RNA and high complexity. Conclusions: The complexity of the hypervariable region 1 quasispecies may be a factor for predicting IFN inefficacy in patients with chronic hepatitis C.