INFLUENCE OF VIRAL QUASI-SPECIES ON EFFECTIVENESS OF INTERFERON THERAPY IN CHRONIC HEPATITIS-C PATIENTS

The quasispecies nature of hepatitis C virus genome distribution is mo st evident in hypervariable regions of the putative envelope 2 domain. Eight patients with chronic hepatitis C treated with interferon-alpha were studied as to heterogeneity of the hypervariable regions to clar ify the implications of quasispecies. More than 10 recombinant clones generated from polymerase chain reaction-amplified products of the hyp ervariable regions were sequenced. The sets of clones derived from lon g-term responders before interferon therapy showed a significantly low er (p < 0.05) degree of sequence complexity of the hypervariable regio n 1 quasispecies than those from short-term ones or non responders. Th e values of nucleotide diversity (the average number of nucleotide dif ferences per site between two randomly chosen sequences) in hypervaria ble region 1 before interferon therapy were also significantly lower ( p < 0.05) for long-term responders (mean, 2.31 x 10(-2)) than for shor t-term ones or nonresponders (13.02 x 10(-2)). In some cases, nucleoti de diversity decreased remarkably during interferon therapy, whereas t he values remained unchanged in other cases. In one interesting case, a short-term response was first noted with the nucleotide diversity de creasing from 13.98 x 10(-2) to 0.21 x 10(-2); namely, the diversity o f the quasispecies was significantly reduced, and then a long-term res ponse was observed after an additional course of interferon therapy. T hus, the degree of quasispecies' complexity and diversity of hypervari able region 1 was closely correlated with the responsiveness to interf eron therapy in chronic hepatitis C patients, and thus may have some i nfluence on interferon efficacy.