Changes in hepatitis C virus quasispecies and density populations in patients before and after interferon therapy

Some chronic hepatitis C patients show sustained response to interferon (IFN) therapy despite viremia. This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (1995): J Med Virol 46:230-237]. To investigate further the relationship between alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifugation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be related to the density populations. Sera were obtained serially from 12 patients who had undergone IFN therapy (six sustained responders with viremia, six nonresponders). During the follow-up after interferon therapy, the HVR heterogeneities changed in 9 of the 12 patients. The remaining three patients whose heterogeneities did not changed persistently showed normal ALT. The changes in HVR heterogeneities were less pronounced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both responders. In two cases, changes in HVR heterogeneities and increase in low-density virion were observed before the hepatitis flare-up. These data indicate that HVR quasispecies show more relation to ALT levels after IFN therapy than HCV density populations and that the changes in the HVR sequences and HCV density populations may be associated with ALT elevation in some patients.