[Genomic changes in the E2/NS1 region of HCV before and after IFN therapy in relation to clinical course]

To estimate the relationship between genomic change in the E2/NS1 region and clinical feature, we made a pairwise comparison in the nucleotide and deduced amino acid sequences for multiple recombinant clones of the E2/NS1 region, which derived from blood samples taken from four patients (three treated by IFN) at different stages. Sequence heterogeneities among the clones were generally high but they appeared to be significantly lowered after cessation of therapy. Our results showed, through IFN therapy, a few clones were selected and survived, although many clones disappeared. After discontinuation of the drug, three patients became carrier state, normal ALT levels with viremia. Evolution of defective viruses was seen in most of the cases. These features of HCV genome suggest that the virus could circulate as an extremely heterogeneous population including defective virus, and that this heterogeneity lend itself to selection pressures including interferon therapy and host immune response.