CHANGES IN HEPATITIS-C VIRUS QUASI-SPECIES AND DENSITY POPULATIONS INPATIENTS BEFORE AND AFTER INTERFERON THERAPY

Some chronic hepatitis C patients show sustained response to interfero n (IFN) therapy despite viremia, This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (199 5): J Med Virol 46:230-237]. To investigate further the relationship b etween alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifu gation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be rela ted to the density populations. Sera were obtained serially from 12 pa tients who had undergone IFN therapy (six sustained responders with vi remia, six nonresponders). During the follow-up after interferon thera py, the HVR heterogeneities changed in 9 of the 12 patients. The remai ning three patients whose heterogeneities did not changed persistently showed normal ALT, The changes in HVR heterogeneities were less prono unced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both respo nders. in two cases, changes in HVR heterogeneities and increase in lo w-density virion were observed before the hepatitis flare-up. These da ta indicate that HVR quasispecies show more relation to ALT levels aft er IFN therapy than HCV density populations and that the changes in th e HVR sequences and HCV density populations may be associated with ALT elevation in some patients. (C) 1996 Wiley-Liss, Inc.