Hypervariable region 1 of hepatitis C virus genome and response to interferon therapy

The relationship between the complexity of the hypervariable region 1 (HVR1 ) quasispecies of hepatitis C virus (HCV) and responsiveness to interferon- alpha (IFN) therapy was studied in patients with chronic hepatitis C. Twelv e HCV-RNA-positive patients were treated daily with high dose IFN and ribav irin for 4 weeks, and then with IFN 3 MIU (Million International Units) TIW (three times per week) and ribavirin for 6 months. The HVR1 quasispecies c omplexity was analyzed by nested polymerase chain reaction-mediated single- strand conformation polymorphism (SSCP). The baseline HCV-RNA levels in the study group ranged from 10(6) to 10(7) copies/ml. All patients exhibited H CV genotype 1 b. Initial SSCP analysis revealed four (33.3%) patients with a low complexity pattern (SSCP bands less than or equal to4) and eight (66. 6%) patients with high complexity pattern (SSCP bands >4). After 4 weeks of IFN therapy, one patient became HCV negative, and among those remaining po sitive, the HCV-RNA levels decreased by 2 to 3 logs and the number of SSCP decreased by 2 to 3 bands per sample. After 6 months of IFN therapy, five ( 41.7%) patients became HCV-RNA-negative. Seven (58.3%) patients did not res pond to IFN therapy with sustained viral load from 10(3) to 10(5) copies/ml , and high complexity SSCP patterns. Our data support the HVR quasispecies complexity to be an independent predictive factor for IFN responsiveness in patients infected with HCV.